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Combining retinol with other ingredients like AHA/BHA or Vitamin C – #AskDoctorAnne
This is actually part two of a three-part series on how to combine ingredients like a pro, And today we're going to talk about retinoids. So if you missed the first episode, I'm going to link it up in the cards and wait patiently for you to come back. Hi, I'm Doctor Anne. I'm a medical doctor with a passion for skincare that works. On this channel We explore the science behind skin and do quick reviews So you'll learn to pick exactly those products that work for your individual skin concern. If this is something you're interested in, please consider subscribing and ring the notification bell. it is important to note that retinol is often used as an umbrella term for a whole family of Retinoids, and which retinol you pick actually makes kind of a huge difference whether or not you can combine it safely with other ingredients. Retinoids are the whole family, while retinol is the most Prominent member of the family and I know this would be the perfect time for a Kardashian family analogy, but I Really don't know anything about them, So I'm going to stick with skincare here. If you want to learn more about the difference between the retinoids, I have a whole video dedicated on that topic that I'm going to link up in the cards, but in short: Retinol and retinal or retinaldehyde and retinol esters like retinol palmitate are over-the-counter Available. They are a weaker form and are usually safe to combine with everything, Adapalene or Differin is available over-the-counter in some parts of the world, in other parts like Germany, it is still prescription, but it is stabilized so it can be combined with other ingredients. Tretinoin or Retin A is Prescription only and it is really unstable, So I would not advise you to mix it with anything. After that has been cleared up, Let's talk about the different actives that you can combine or cannot combine your retinoids with. And just to make that crystal clear: if I am talking about mixing your retinoids with other active ingredients, I always refer to over-the-counter retinoids Always! Never mix a prescription on your own terms, Always consult a professional! I can't stress that enough: There's a reason why some things are prescription! And no, watching a doctor on YouTube is not the same as talking to the person that Actually prescribed your medication. So the first thing that people like to combine their retinoids with is acids. AHAs or BHAs and while that's technically possible, I still don't think that it is Advisable. Why? well, they don't really interfere with each other, So if you use a retinoid and then you use an acid or vice versa that will not really hinder the effects. But because retinoids increase cell turnover and acids increase Exfoliation both can lead to shedding and flakiness on the skin. So if you combine these two, you can actually Enhance the shedding of flakiness on your skin, which is not a good look. And you can enhance the irritation that your skin experiences, so my advice would be: First start your retinoid until you have zero Irritation and then slowly pair it with an exfoliating acid, if you really think that you need one. Once you build up your tolerance, Slowly start to introduce them once a week – I don't think you need more – maybe twice a week, Anything else is too much. And if you want to know more about introducing retinoids into your routine, I have a whole video on that topic that I'm going to link up in the cards. The next ingredient that I got quite a few questions on was vitamin C, and I'm going to do a whole video on vitamin C and what to look for when pairing it, but while in theory It's safe to pair vitamin C with retinoids I would not use them at the same time in my routine, because vitamin C has a low pH, retinoids have a more neutral pH. I don't think that this matters too much, but the vitamin C can be irritating and the retinoids can be Irritating. Mixing two irritating ingredients increases the risk for more irritation on your skin, So I advise you to use your vitamin C in the mornings, your retinoids at night And you should be good to go. Next thing is benzoyl peroxide. You can mix Over-the-counter retinoids with benzoyl peroxide, but benzoyl peroxide is really really irritating, it's really drying on the skin, So I would suggest using that only as advised by your doctor, because it can Maximize the irritation that you get. It is however safe to use with over-the-counter retinoids and with Adapalene. Niacinamide is an ingredient that actually helps because it has shown to improve the skins Resilience and reduce the retinoid irritation that many people experience, So niacinamide is a do. Use niacinamide in the same routine, in the same products as you use your retinoids, that will actually grant you more benefits. And as far as peptides and Ceramides go: you can use ceramides after or in conjunction with your retinoid, You can use your peptides as well, Because they don't really interfere with each other. If you want to be on the safe side you use your peptides as part of your humectant serum in the mornings and use your Retinoid at night. As far as hydroquinone goes: I would never mix hydroquinone with any retinoid. In Germany and the European Union Hydroquinone is prescription only. I know that it's available over-the-counter in other countries, But I think hydroquinone is a very difficult ingredient to mix, It's a difficult ingredient to use, and I would only ever do so under supervision of a professional. I hope that answered some of your questions. If there are any more, please leave them in the comments below. I'm going to link to the other videos with my Ask Doctor Anne series on the screen now And I'm going to see you all very soon with another one. Bye!


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Preparation and in vitro antioxidant activity of some novel flavone analogues bearing piperazine moiety
Preparation and in vitro antioxidant activity of some novel flavone analogues bearing piperazine moiety
Preparation and in vitro antioxidant activity of some novel flavone analogues bearing piperazine moiety
Bioorganic Chemistry 95 (2020) 103513 Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioor...
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Bioorganic Chemistry 95 (2020) 103513
Contents lists available at ScienceDirect
Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg
Preparation and in vitro antioxidant activity of some novel flavone analogues bearing piperazine moiety
Paweł Berczyńskia, Aleksandra Kładnab, Oya Bozdağ Dündarc, Hatice Nehir Muratc, Elmas Sarıc, ⁎ Irena Kruka, Hassan Y. Aboul-Eneind, a
Institute of Physics, Faculty of Mechanical Engineering and Mechatronics, West Pomeranian University of Technology in Szczecin, Al. Piastów 48/49, 70-311 Szczecin, Poland b Department of History of Medicine and Medical Ethics, Pomeranian Medical University, Rybacka 1, 70-204 Szczecin, Poland c Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Tandoğan, Ankara, Turkey d Pharmaceutical and Medicinal Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, Egypt
Keywords: Piperazinyl flavone analogues Free radical inhibitory activity Antioxidant activity Chemiluminescence Electron spin resonance
Background: A series of eight new flavone derivatives containing a piperazine chain with different substitution were synthesized and their structures were determined. Methods: Their antiradical and antioxidant activities were evaluated using superoxide anion radical, hydroxyl radical, 2,2-diphenyl-1-picrylhydrazyl radical, 2,2′-azino-di(3-ethylbenzthiazoline sulphonate) radical cation (ABTS+%) scavenging (as measure total antioxidant status TAS), ferric reducing antioxidant power (TAC), and hydrogen peroxide decomposition. The antioxidant activities of the synthesized compounds were compared with standard antioxidants trolox, ascorbic acid, butylated hydroxytoluene (BHT) as positive controls, reference antibiotics (doxycycline, dicloxacillin), and medicinal plants (Menthae piperita, Cistus incanus). Chemiluminescence, spectrophotometry, electron spin resonance (ESR) spectroscopy in conjunction with 5,5dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap were the measurement techniques. Results: The results show that the synthesized compounds exhibit weak, albeit a wide spectrum of antiradical and antioxidant activities. The TAS values were measured as trolox equivalents, ranging from 209.6 ± 6.1 to 391.1 ± 8.2 µM TE/g; the TAC values were in ranges from 10.8 ± 0.5 to 49.5 ± 0.5 µM TE/g being higher than that of dicloxacillin (241.0 ± 16.5 and 9.73 ± 0.8 µM TE/g, respectively), but lower than ascorbic acid, BHT, doxycycline, and medicinal plants. Best antioxidant activities were found for the piperazinyl analogues with methoxy group on phenyl piperazine ring. Conclusion: We suggest that the synthesized compounds may be used as lead molecules for optimization of molecular structure to maximize the antioxidant potency.
1. Introduction The cellular damage caused by oxidative stress (OS) and its main contributing factors, i.e. excess of reactive oxygen species (ROS) (superoxide anion radical, O2¯ ; hydroxyl radical, HO%; and hydrogen peroxide, H2O2); and reactive nitrogen species (RNS), (nitric oxide, NO% and peroxynitrite, ONOO−) as well as too low activity of the cellular antioxidant systems to repair the cellular injury has been linked with
many chronic diseases and ageing [1–4]. During the past years the protective effects of antioxidants against the OS related pathophysiologies and antioxidant therapies have received increasing attention within medical field. Flavones are a group of naturally occurring compounds belonging to a large flavonoid family which has been found in all plants [5–7]. The group shows, among other, antioxidant activities against a wide spectrum of free radicals and non – radical ROS and strong protective effects against OS, offering reduction of the
Abbreviations: ABTS, 2,2′-azino-di(3-ethylbenzthiazoline sulphonate); ARP, antiradical power; BHT, butylated hydroxytoluene; CL, chemiluminescence; DMPO, 5,5dimethyl-1-pyrroline-1-oxide; DMSO, dimethyl sulfoxide; DPPH, 2,2-diphenyl-1-picrylhydrazyl; ESR, electron spin resonance; HO⋅, hydroxyl radical; H2O2, hydrogen peroxide; NMR, nuclear magnetic resonance; 1O2, singlet oxygen; O2¯· , superoxide anion radical; RNS, reactive nitrogen species; ROS, reactive oxygen species; SPF, substituted piperazinyl flavone; SV, stechiometric value; TAC, total antioxidant capacity; TAS, total antioxidant status ⁎ Corresponding author at: Pharmaceutical and Medicinal Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza 12622, Egypt. E-mail address:
[email protected]
(H.Y. Aboul-Enein). https://doi.org/10.1016/j.bioorg.2019.103513 Received 17 September 2019; Received in revised form 16 November 2019; Accepted 16 December 2019 Available online 21 December 2019 0045-2068/ © 2019 Elsevier Inc. All rights reserved.
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P. Berczyński, et al.
civilization diseases risk [7–11]. They include anti – inflammatory, antimicrobial, antipathogenic, antiviral, anti-atherosclerotic, anticancer and cardioprotective effects. Evidence showed promotion of apoptosis of cancer cells such as prostate, lung and skin by natural and some of synthetic flavones [12]. The findings show the structure activity relationships: compounds having electron donating groups (eOH, eOCH3) on the phenyl ring favoured the antioxidant behaviour, while electron withdrawing atoms/groups (eF, eCl, eBr, eNO2) favoured the anti – inflammatory activity [13–15], and the presence of fluorine atom and SO2 group increases antioxidant and anti – inflammatory activities [13,16]. Several research laboratories in the world have focused on the synthesis effective plant derived compounds and their synthetic analogues as the potential therapeutics exhibiting antioxidant and anti – inflammatory activities. Importantly, sulfonyl, sulfonoamide [16], amino acids/peptides conjugated heterocycles [17] or benzisoxazole analogs [18] were developed as new candidates for less toxic drugs, among others. Similarly, piperazine and its derivatives are biologically active compounds displaying a broad range of activities, such as antioxidant and anti-inflammation, being recently used as anticancer and antibacterial agents [19–21]. An interesting research by Karthik and coworkers [22] showed novel compounds having piperazine in their structures (benzodioxane midst piperazine, BP and BP decorated chitosan silver nanoparticles) exhibit anti – inflammatory and anticancer properties among others. On the basis of these properties, incorporation of isoflavones and piperazines consists an important aspect of medicinal chemistry in developing of new antioxidant –based drugs. Based on the above facts and continuing our research program aimed in developing efficient synthesis of pharmacological useful new antioxidants, some new substituted piperazinyl flavones (SPF) were synthesized (Table 1) and their antioxidant activity in vitro was determined.
(Cistus incanus) collected in Turkey from Intenson Europe and (Menthae piperitae) collected in Poland were supplied from the local food market in Szczecin (Poland). 2.1.1. Preparation of the target compounds General procedure for preparation of SPF compounds studied is shown in Scheme 1. All synthesized compounds are novel. The general method which is known as Baker-Venkataraman method [23] was used to prepare 3′/4′-methyl flavone (Ia-b). The methyl group of the flavone was converted to bromomethyl (IIa-b) with N-bromosuccinimide (NBS) and a catalytic amount of benzoyl peroxide. Tert-butyl 4-(3 or 4-(4-oxo-4H-chromen-2-yl)benzyl)piperazine-1carboxylate (3B, 4B) was synthesized with 3′/4′-bromomethyl flavone IIa-b and tert-butyl piperazine-1-carboxylate, in the presence of Na2CO3/acetonitrile. The acidic hydrolysis of 3B, 4B provided corresponding piperazinylflavones 3H, 4H. Piperazinylflavone derivatives 4PP, 3PP, 4FCO, 3FCO, 43FMCO, 33FMCO, 4FBCO and 425 M were synthesized with 3H or 4H and appropriate substituted benzoyl halide or phenacylhalide in alkaline medium. 188.8.131.52. Synthesis of 3′ (IIa)-4′ (IIb)-bromomethyl flavone. A mixture of N-bromosuccinimide (1.2 g, 6.72 mM) and 3′ (Ia)/4′-methyl flavone (Ib) (1.0 g, 4.2 mM) was dissolved in 70 mL of carbon tetrachloride and benzoyl peroxide (0.1 g) was added. The reaction mixture was refluxed for 7 h and filtered while it was still hot. The crude product was crystallized from ethylacetate: n-hexane. IIa m.p:154 °C (m.p.:137 °C[24]), IIb m.p.:158 °C (m.p.:139 °C [24]). 184.108.40.206. General synthesis of tert-butyl 4-(3 (or 4)-(4-oxo-4H-chromen-2yl)benzyl)piperazine-1-carboxylate (3B-4B). A mixture of 3′/4′bromomethyl flavone IIa-b (0.50 g, 1.19 mM), tert-butyl piperazine-1carboxylate (0.29 g, 1.58 mM), Na2CO3 (0.16 g, 1.19 mM) and 10 mL acetonitrile was stirred at room temperature for 48 h. The reaction mixture was filtered, concentrated in vacuum, and then purified by column chromatography Silica gel 60 (230–400 mesh ASTM) using nhexane: ethylacetate (3: 1) as eluent.
2. Materials and methods 2.1. Reagents All the chemicals and reagents used in the study were of analytical grade and purchased from E. Merck (Darmstadt, Germany). The set of reagents for the quantitative determination of Total Antioxidant Status was obtained from Randox (UK). Commercial samples of herbal tea
184.108.40.206. Tert-butyl 4-(3-(4-oxo-4H-chromen-2-yl)benzyl)piperazine-1carboxylate (3B). Yield: 0.48 g; 72.72%, m.p.: 113 °C (m.p.: 113 °C [24]).
Table 1 Piperazinyl flavone compounds.
Bioorganic Chemistry 95 (2020) 103513
P. Berczyński, et al.
Scheme 1. Synthesis of piperazinyl flavone compounds.
22.214.171.124. tert-butyl 4-(4-(4-oxo-4H-chromen-2-yl)benzyl)piperazine-1carboxylate (4B). Yield: 0.49 g; 74.24%, m.p.: 138 °C (m.p.: 138 °C [24]).
mixture was evaporated in vacuum, water added and extracted with CHCl3 (3x50 mL). The organic layer was dried over anhydrous Na2SO4, evaporated to dryness and then purified by column chromatography Silica gel 60 (230–400 mesh ASTM) using dichloromethane: isopropanole (10: 1) as eluent. The pure viscous oil product was precipitated by adding ethylacetate.
220.127.116.11. General synthesis of 3′/4′-(piperazin-1-ylmethyl)flavone (3H, 4H) [25]. A mixture of 3B-4B (0.48 g, 1.49 mM), 5 mL dioxane and 5 mL 4 M HCl was stirred at room temperature for 5 h. The solution of 10% Na2CO3 was added into the reaction mixture up to alkaline pH. This mixture was washed three times with CHCl3, and the combined organic extracts were washed with water. The organic phase was dried over Na2SO4, concentrated in vacuum, and then purified by column chromatography Silica gel 60 (230–400 mesh ASTM) using CHCl3: isopropanol: ammonium hydroxide solution (26–30%) (10:1:0.3) as eluent.
22.214.171.124. 2-(4-((4-(benzo[d][1,3]dioxole-5-carbonyl)piperazin-1-yl) methyl)phenyl)-4H-chromen-4-one (4PP). Yield: 94%, m.p.: 141 °C. Spectroscopic analysis: 1H NMR (CDCl3, 400 MHz,δ, ppm): 2.48(broad, s, 4H, piperazine-CH2), 3.61(broad, s, 6H, piperazineCH2, fl-CH2), 5.98(s, 2H, O-CH2-O), 6.79–6,82 (m, 2H, 7′',3-H), 6.89–6.92(m, 2H, 4′',6′'-H), 7.42 (td, 1H, 6-H), 7.48–7.50 (m, 2H, 4′, 5′-H), 7.57(d, 1H, j8,7 = 8.40 Hz, 8-H), 7.69(td, 1H, 7-H), 7.88–7.89(m, 2H, 2′,6′-H), 8.23(d, 1H, j5,6 = 8.00 Hz, 5-H). MS (ESI + ) m/z (rel. Intensity): 469.4 (M + H, 100%); Anal. Calcd. for C28H24N2O4 C: 70.30, H: 5.51, N: 5.47%; found: C: 70.47, H: 5.54, N: 5.70%.
18.104.22.168. 3′ – (piperazin-1-ylmethyl)flavone (3H). Yield: 0.30 g ; 81.08%, m.p.: 95 °C (m.p.: 95 °C [25]). 184.108.40.206. 4′-(piperazin-1-ylmethyl)flavone (4H). Yield: 0.31 g ; 83.78%, m.p.: 100 °C (m.p.: 100 °C [25]).
184.108.40.206. 2-(3-((4-(benzo[d][1,3]dioxole-5-carbonyl)piperazin-1-yl) methyl)phenyl)-4H-chromen-4-one (3PP). Yield: 89%, m.p.: 165 °C. Spectroscopic analysis: 1H NMR (CDCl3, 400 MHz,δ, ppm): 2.49(broad, s, 4H, piperazine-CH2), 3.61(broad, s, 4H, piperazineCH2), 3.63(s, 2H, fl-CH2), 5.97 (s, 2H, O-CH2-O), 6.79 (d, 1H, 7′'-H), 6.82(s, 1H, 3-H), 6.89–6.92(m, 2H, 4′',6′'-H), 7.41 (td, 1H, 6-H), 7.45–7.48 (m, 2H, 4′, 5′-H), 7.57(d, 1H, j8,7 = 8.80 Hz, 8-H), 7.69(td, 1H, 7-H), 7.81–7.83(m, 1H, 6′-H), 7.88(s, 1H, 2′-H), 8.22(d,
22.214.171.124. General synthesis of benzylsubstituted piperazin-1-ylmethyl flavones 4PP, 3PP, 4FCO, 3FCO, 43FMCO, 33FMCO, 4FBCO and 425 M. A mixture of 3′/4′-piperazinomethyl flavone 3H/4H (0.4 mM), substituted benzoylbromide (0.4 mM), Na2CO3 (0.4 mM) and 10 mL acetonitrile were stirred at room temperature for 12 h. The reaction 3
Bioorganic Chemistry 95 (2020) 103513
P. Berczyński, et al.
1H, j5,6 = 8.00 Hz, 5-H). MS (ESI + ) m/z (rel. Intensity): 469.2 (M + H, 100%); Anal. Calcd. for C28H24N2O5-0,35C4H8O2 C: 70.72, H: 5.41, N: 5.61%; found: C: 70.86, H: 5.42, N: 5.77%.
CH2), 2.78 (s, 1H, piperazin-CH2), 2.85 (s, 1H, piperazin-CH2), 3.54 (s, 2H, fl-CH2), 3.68 (s, 3H, OCH3), 3.76 (s, 2H, COCH2), 3.77 (s, 3H, OCH3), 6.71 (s, 1H, 3-H), 6.80 (d, 1H, Ar-H), 6.92(dd, 1H, Ar-H), 7.21 (d, 1H, Ar-H), 7.32 (t, 1H, 6-H), 7.42 (d, 2H, jo = 8.40 Hz, 3′,5′-H), 7.47(d, 1H, j8,7 = 8.40 Hz, 8-H), 7.60 (td, 1H, 7-H), 7.78(d, 2H, jo = 8.40 Hz, 2′,6′-H), 8.12 (dd, 1H, j5,6 = 8.00 Hz, j5,7 = 1.20 Hz, 5H). MS (ESI + ) m/z (rel. Intensity): 441.6 (M + H, 100%); Anal. Calcd. for C30H30N2O5.
188.8.131.52. 2-(4-((4-(4-fluorobenzoyl)piperazin-1-yl)methyl)phenyl)-4Hchromen-4-one (4FCO). Yield: 88%, m.p.: 164 °C. Spectroscopic analysis: 1H NMR (CDCl3, 400 MHz,δ, ppm): 2.49 (broad s, 4H, piperazine-CH2), 3.48 (broad s, 2H, piperazine-CH2), 3.62 (s, 2H, flCH2), 3.78 (broad s, 2H, piperazine-CH2), 6.82 (s, 1H, 3-H), 7,06–7,10 (m, 2H, Ar-H), 7,39–7,44 (m, 3H, Ar-H, 6-H), 7.49 (d, 2H, jo = 8.40 Hz, 3′,5′-H), 7.56 (d, 1H, j8,7 = 8.80 Hz, 8-H), 7.70 (td, 1H, 7-H), 7.89 (d, 2H, jo = 8.0 Hz, 2′,6′-H), 8.23 (d,1H, j5,6 = 8 Hz, 5-H). MS (ESI + ) m/z (rel. Intensity): 443,2 (M + H, 100%); Anal. Calcd. for C27H23FN2O30,2H2O C: 72.69, H: 5.29, N: 6.28%; found: C: 72.65, H: 5.56, N: 6.11%.
2.1.2. Procedures for preparation free radicals The superoxide anion radical (O2¯ ) was prepared from KO2 according to the procedure of Valentine et al.[26]. Initially, 60 mg of 18-crown-6 ether was dissolved in 10 mL dry DMSO and 7 mg of KO2 was added quickly to avoid contact with the air humidity. The reaction mixture was stirred for 1 h to give a pale yellow solution of 10 mM superoxide radical which was stable at room temperature. The radical concentration was measured with the UV–VIS spectrophotometer (λmax = 251 nm, ε = 2686 ± 29 M−1 cm−1). For the experiments, O2¯ was used as a 1 mM solution in DMSO. Hydroxyl radicals (HO%) were generated in the Fenton reaction (H2O2 + Fe(II) → HO. + Fe(III) + HO−) [27,28].
220.127.116.11. 2-(3-((4-(4-fluorobenzoyl)piperazin-1-yl)methyl)phenyl)-4Hchromen-4-one (3FCO). Yield: 87%, m.p.: 75 °C. Spectroscopic analysis: 1 H NMR (CDCl3, 400 MHz,δ, ppm): 2.55(broad s, 4H, piperazine-CH2), 3.49(broad s, 2H, piperazine-CH2), 3.65(s, 2H, fl-CH2), 3.81(broad s, 2H, piperazine- CH2), 6.86(s, 1H, 3-H), 7.08–7.12(m, 2H, Ar-H), 7,42–7,53(m ,5H, Ar-H, 6, 4′, 5′H), 7.61(d, 1H, j8,7 = 8.40 Hz, 8-H), 7.73(td, 1H, 7-H), 7.84–7.87(m, 1H, 6′-H), 7.91(s, 1H, 2′-H), 8.25(dd, 1H, j5,6 = 8.00 Hz, j5,7 = 1.20 Hz, 5-H). MS (ESI + ) m/z (rel. Intensity): 443,2 (M + H, 100%); Anal. Calcd. for C27H23FN2O3-1,2H2O C: 69.87, H: 5.51, N: 6.04%; found: C: 69.79, H: 5.20, N: 6.09%.
2.1.3. Preparation of herbal teas infusions 1.5 g of the commercial Menthae piperitae and Cistus incanus were dipped separately into 100 mL of freshly boiled redistilled water in a beaker, shaken and allowed to stand for 10 min. Next tea infusions were allowed to cool to room temperature and filtered through a Whatman filter paper.
184.108.40.206. 2-(4-((4-(4-(triflorometoksy)benzoil)piperazin-1-il)methyl) fenyl)-4H-kromen-4-on (43FMCO). Yield: 95%, m.p.: 143 °C. Spectroscopic analysis: 1H NMR (CDCl3, 400 MHz,δ, ppm): 2.45(broad s, 2H, piperazine- CH2), 2.55(broad s, 2H, piperazineCH2), 3.45(broad s, 2H, piperazine-CH2), 3.62(s, 2H, fl-CH2), 3.80(broad s, 2H, piperazine-CH2), 6.82(s, 1H, 3-H), 7,24(d,2H,Ar-H) 7,40–7,46(m,3H,Ar-H,6-H) 7.49(d, 2H, jo = 8.0 Hz, 3′,5′-H), 7.56(d, 1H, j8,7 = 8.80 Hz, 8- H), 7.70(td, 1H, 7-H), 7.89(d, 2H, jo = 8.0 Hz, 2′,6′-H), 8.23(dd,1H, j5,6 = 8.00 Hz, j5,7 = 1.20 Hz,5-H). MS (ESI + ) m/z (rel. Intensity): 509,3 (M + H, 100%); Anal. Calcd. for C28H23FN2O4 C: 66.14, H: 4.73, N: 5.64%; found: C: 66.14, H: 4.73, N: 5.64%.
2.2. Apparatus Melting points of the compounds were measured on an Electrothermal 9100 type apparatus (Electrothermal Engineering, Essex, UK) and uncorrected. All instrumental analyses were performed in Central Laboratory of Faculty of Pharmacy of Ankara University. 1H NMR spectra were determined with a VARIAN Mercury 400 FT-NMR spectrometer (Varian Inc, Palo Alto, CA, USA) in CDCl3 and DMSO‑d6. All chemical shifts were reported as δ (ppm) values. Mass spectra were recorded on Waters Micromass ZQ (Waters Corporation, Milford, MA, USA) by using ESI (+) method. Elementary analyses were performed on a Leco CHNS 932 analyzer (Leco, St. Joseph, USA) and satisfactory results ± 0.4% of calculated values (C, H, N) were obtained. For the chromatographic analysis Merck Silica Gel 60 (230–400 mesh ASTM) was used. The chemiluminescence (CL) measurements were performed using a luminometer equipped with an EMI 9553Q photomultiplier (Photek, East Sussex, UK) with a S20 cathode sensitive in the range 200–800 nm. A thermostated glass cuvette placed in a light-tight camera was exhausted after reaction using a B-169 vacuum system (Büchi, Flawill, Switzerland). The measurements were carried out at room temperature. Spectrophotometric measurements were performed using a UV/VIS spectrophotometer equipped with a thermostat bath (Jasco V-550). Electron spin resonance (ESR) spectra were recorded with a standard X-band spectrometer operating at 9.3 GHz with a 100 kHz modulation of the steady magnetic field. Samples were introduced into the cavity in a quartz cuvette with an optical path length of 0.25 mm and recorded after 1 min from the start of a reaction and analyzed every one minute. The majority of the data are presented as a mean ± standard error of the mean. With the exception of the total antioxidant status (TAS) evaluation, the remaining experiments were carried out at room temperature. Statistical evaluation was carried out using the basic statistics and regression analyses using the statistical package STATISTICA 6.0 2002 (StatSoft Polska, Kraków). A p-value < 0.05 was considered to be significant.
22.214.171.124. 2-(3-((4-(4-(triflorometoksy)benzoil)piperazin-1-il)methyl) fenyl)-4H-kromen-4-on (33FMCO). Yield: 93%, m.p.: 138 °C. Spectroscopic analysis: 1H NMR (CDCl3, 400 MHz,δ, ppm): 2.45(broad s, 2H, piperazine-CH2), 2.57(broad s, 2H, piperazine-CH2), 3.46(broad s, 2H, piperazine-CH2), 3.64(s, 2H, fl-CH2), 3.81(broad s, 2H, piperazine-CH2), 6.84(s, 1H, 3-H), 7,24(d, 2H, Ar-H), 7.41–7.50(m, 5H, Ar,4′,5′,6-H) 7.58(d, 1H, j8,7 = 8.0 Hz, 8-H), 7.71(td, 1H, 7-H), 7.84(d, 1H, 6′-H), 7.90(s, 1H, 2′-H), 8.23(d, 1H, j5,6 = 8.00 Hz, 5-H). MS (ESI + ) m/z (rel. Intensity): 509 (M + H, 100%); Anal. Calcd. for C28H23FN2O4 C: 65.38, H: 4.85, N: 5.15%; found: C: 65.08, H: 4.76, N: 5.45%. 188.8.131.52. 2-(4-((4-(2-(4-fluorophenyl)-2-oxoethyl)piperazin-1-yl)methyl) phenyl)-4H-chromen-4-one (4FBCO). Yield: 84.11%, m.p.: 123 °C. Spectroscopic analysis: 1H NMR (CDCl3, 400 MHz,δ, ppm): 2.62 (broad s, 4H, piperazine-CH2), 3.67 (broad s, 4H, piperazineCH2), 3.63 (s, 2H, fl-CH2), 3.79 (s, 2H, COCH2), 6.82 (s, 1H, 3-H), 7.09–7.14 (m, 2H, Ar-H) , 7.42 (td, 1H, 6-H),7.51 (d, 2H, jo = 7.60 Hz, 3′,5′-H), 7.57 (d, 1H, j8,7 = 8.80 Hz, 8-H), 7.710 (td, 1H, 7-H), 7.89 (d, 2H, jo = 8.00 Hz, 2′,6′-H), 8.02–8.06 (m, 2H, Ar-H), 8.23 (dd,1H, j5,6 = 8.00 Hz, j5,7 = 1,60 Hz,5-H). MS (ESI + ) m/z (rel. Intensity): 457.5 (M + H, 100%); Anal. Calcd. for C28H25FN2O3. 18.104.22.168. 2-(4-((4-(2-(2,5-dimethoxyphenyl)-2-oxoethyl)piperazin-1-yl) methyl)phenyl)-4H chromen-4-one (425 M). Yield: 56.22%, m.p.: 128 °C. Spectroscopic analysis: 1H NMR (CDCl3, 400 MHz,δ, ppm): 2.53 (broad s, 3H, piperazin-CH2), 2.61 (broad s, 3H, piperazin4
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2.3. Antioxidant assays
were plotted for the compound tested concentration in the range of 0.125 – 1.25 mM and the percentage of DPPH% remaining at the steady state was read. Then, the percentage of DPPH% was plotted as function of the molar ratio of the tested compound to DPPH%, according to the procedure of Brand – Williams et al.[32]. From the graph, the Efficient Concentration (EC50) value specifying the concentration of an antioxidant sample that causes a 50% decrease of ESR signal amplitude compared with the amplitude of the untreated reference reaction (M antioxidant/M DPPH%) was determined. Also, the antiradical power (ARP) defined as 1/EC50 (the value directly proportional to antioxidant activity), stoichiometric value (SV = 2EC50) describing the theoretical efficient concentration of antioxidant necessary to scavenge 100% of the initial DPPH%, and the number of reduced DPPH radicals calculated as 1/SV were obtained for a few tested compounds and the reference compounds. Ascorbic acid and BHT were used as the positive controls.
2.3.1. Reactivity of SPF towards the superoxide anion radical Reactivity of synthesized compounds towards O2¯ was examined in DMSO in the range from 0.1 to 0.5 mM using 1 mM O2¯ . The resulting CL signal from the O2¯ solution (blank) and that influenced by the tested compounds were recorded as the kinetic curves of the CL decay. Then the CL intensity sums were calculated as the area under these curves for 5 min duration. The effects were expressed as the enhancing ratio Q (%) of the light sum as follows: Q (%) = [(ΣI − ΣI0)/ΣI0] × 100%, where ΣI0 is the integrated light intensity measured in the absence of SPF compound but in the presence of 0.5 mL of DMSO, and ΣI is the sum measured in the presence of the compound. 2.3.2. Hydrogen peroxide scavenging assay The H2O2 scavenging ability was measured by monitoring the response of CL accompanying H2O2 – induced oxidation of luminol using a previously described by Tao et al. assay [29]. Reaction mixture contained the following reagents at the given final concentrations: 100 μM of luminol, 5 mM H2O2, and phosphate buffer pH 7.0. The reaction was initiated by an addition of H2O2 , and 15 s after the start of the light emission and reaching maximal intensity 0.5 mM of a test compound dissolved in DMSO or the same volume of alone DMSO was added to the reaction mixture. Effects were expressed as the percentage of the H2O2 – induced oxidation of luminol or the standard compound (ascorbic acid) Q (%) = [(ΣI0 − ΣI)/ΣI0] × 100%, where ΣI0 is the CL sum of the control, and ΣI is the CL sum in the presence of the tested compounds or the standard.
2.3.5. Determination of total antioxidant status (TAS) Total antioxidant activity of the examined compounds was measured using the TAS RANDOX kit (Cat. No.NX2332, Randox Laboratories Ltd., Co. Antrim, UK), in accordance with the instruction. The method is based on reduction of 2,2′-azino-di(3-ethylbenzthiazoline sulfonate) radical cation (ABTS+%) to an extent dependent on the antioxidant potential [33]. This cation radical is formed in the reaction of one-electron oxidation of ABTS during incubation with a peroxidase (metmyoglobin) and H2O2. A degree of suppression of the radical cation was compared to the antioxidant activity of standard concentrations of Trolox and expressed in the units of µM Trolox equivalent (TE) per gram of the tested compound dry mass. Ascorbic acid, BHT, dicloxacillin, doxycycline, menthae piperitae, and cistus incanus were used as the positive controls.
2.3.3. Hydroxyl radical scavenging assay The HO% scavenging activity was evaluated by using the Fenton reaction and DMPO as a spin-trap, according to a previously described method [30]. The method allows to detect a short-lived HO% forming with the spin-trap a more stable free radical as DMPO ─ %OH adduct. Reaction mixture contained the following reagents at the final concentrations: 10 mM sodium trifloroacetate (pH 6.15), 25 mM DMPO, 0.5 mM H2O2, 0.625 mM ammonium-ferrous sulfate, and the tested compounds (dissolved in DMSO due to their insolubility in water). The tested compounds were added before the Fe ion addition, which starts the Fenton reaction. After mixing reagents, the mixture was transferred to an ESR spectrometry cell and one min after ESR spectrum was recorded. The known antioxidants BHT and thiourea were used as the positive controls. The results were expressed as a percentage of the signal inhibition using a formule: Q (%) = [(H0 − H)/H0] × 100%, where H0 and H represent the relative height of the spin – adduct from the blank (DMSO) and in the presence of a sample of the tested compound dissolved in an appropriate amount of DMSO, respectively. Measurement conditions of ESR were: field weep 330.5–340.5 mT, field modulation with 0.5 mT, time constant 0.3 s, microwave power 20 mW, and receiver gain 2x104.
2.3.6. Ferric reducing ability measurements (TAC) The reducing activity was evaluated by monitoring the reduction of the Fe(III) – ferrozine agent to stable Fe(II)- ferrozine complex according to a described procedure by Berker et al. [34]. The ferric-ferrozine complex contained of the following reagents at the indicated final concentrations: 2 mM Fe(III) and 10 mM ferrozine. The complex was prepared as follows: the water solution of 0.024 g of NH4 Fe (SO4)2·12H2O after an addition of 1 mL HCl (1 M) was mixed with a separate prepared aqueous solution of 0.123 g ferrozine. The mixture was diluted to 25 mL with distilled water. Then, 0.5 mL of a tested compound dissolved in DMSO was mixed with 1.5 mL of ferric-ferrozine solution and 2 mL of acetate buffer pH 5.5 (0.2 M). To obtain the final required volume 4.5 mL, 0.5 mL of water was added. The mixture was shaken vigorously and allowed to stand at 25 °C for 1 h. The spectrophotometric assays were performed at the absorption wavelength 562 nm. Ascorbic acid, BHT, dicloxacillin, doxycycline, menthae piperitae and cistus incanus were used as the positive controls. The reducing activity was expessed in the units of µM Trolox Equivalent (TE) per gram of the tested compound dry mass.
3. Results and discussion
2.3.4. 2,2 - diphenyl – 1-picrylhydrazyl radical scavenging activity The DPPH% scavenging activity was measured using a previously described methodology by Nanjo et al. [31] with the small modification, i.e. the solvent mixture DMSO:C2H5OH(1:3) was used instead of ethanol. The method is based on spectroscopic monitoring changes of a stabile DPPH free radical in the presence of antioxidants. The tested compounds dissolved in DMSO at various concentrations were mixed with ethanolic solution of DPPH (0.25 mM final concentration) and a decrease in ESR spectrum amplitude was detected. The decrease in a spectrum amplitude was monitored until the reaction reached a plateau. The scavenging activity of the tested compounds towards DPPH% was calculated using the following equation: Q (%) = [(H0 – H)/ H0] × 100%, where H0 is the relative height of the third peak in the ESR spectrum in the absence of a test compound, H is the relative height of the third peak in the presence of the compound. The reaction kinetics
The synthetic routes for the newly synthesized compounds are presented in the Scheme 1 and described in the Materials and Methods. The structure of the synthesized compounds was elucidated by elementary analysis, 1H NMR, and mass spectral data. All spectral data were in accordance with assumed structures. In 1H NMR spectra, flavone protons were observed between 6.79 and 8.25 ppm (see Supplementary data). Mass analysis of compounds was performed by using ESI (+) method. All the compounds have M + H ion peaks. The series of a novel group of piperazinyl flavones were evaluated as possible antioxidant agents by performing various tests, like reactivity towards: O2¯ , HO%, DPPH%, ABTS%+, and H2O2. Additionally, the ability to reduce Fe(III) ion to Fe(II) ion, which is a significant indicator of antioxidant potency, was evaluated using the Fe(II) – ferrozine complex 5
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[34]. The results are compared with those obtained for several standard antioxidants, antibiotics and medicinal plants. The O2¯ , H2O2 and HO% are produced during endogenous metabolic processes in the human body as the normal product of one – electron reduction of molecular oxygen (O2) and also are formed from external sources, like environment pollution or radiation [1,35]. The O2¯ radical is known as precursor of more chemically active HO% and singlet oxygen (1O2) formed in biological system [36,37]. The oxygen free radicals are short – lived and highly reactive; they can behave as oxidants or reductants and cause damage of the cellular macromolecules, like nucleic acids, lipids, proteins, and carbohydrates [1,3]. An imbalance between formation of ROS and antioxidant defenses with a predominance of oxidation processes is known in literature as oxidative stress (OS) that has been reported to contribute to several serious diseases, including cancer and premature aging [38,39]. Compounds showing antioxidant activity act, among other, as direct radical scavengers, hydrogen or electron donors or peroxide decomposers. We found previously that 1O2 is responsible for CL accompanying the O2¯ /DMSO system detecting four emission bands with maxima at 480 nm, 580 nm, 640 nm, and 700 nm which can result from radiative deactivation of 1O2 – dimoles (1O2)2 to the ground state (3O2) [40]. In agreement with reactivity of O2¯ in DMSO [41], the increased light emission (Fig. 1) in the presence of SPF compounds may be due to the proton transfer to the anion radical followed by hydroperoxyl radical (HO2· ) formation
Fig. 2. Hydrogen peroxide and hydroxyl radical inhibitory activity at concentration 0.5 mM and 1.25 mM of piperazinyl flavones, respectively. Data are represented as mean ± S.D.(n = 3). The chemiluminescence and electron spin resonance signals were measured as explained under Materials and Methods. Denotations of the compounds are shown in Table 1.
groups in structure of the tested compounds. In addition, the compounds having substitution R at position 4′ (Table 1) were found to be more reactive than those with substitution at position 3′. This suggests that the stabilization of the products formed from FSP transformation is higher for R attached to the chromone skeleton at position 4′. This suggestion agrees with Phosrithong et al.' findings [43] that the chromone skeleton plays only role of a stabilizer during the hydrogen or/ and electron transfer to a free radical. The behaviour of SPF compounds reminds that of superoxide dismutase, an enzyme which transforms O2¯ to H2O2. The ability of SPF compounds to scavenge hydrogen peroxide and hydroxyl radical is presented in Fig. 2. The H2O2 scavenging ability of SPF compounds was detected using a previously described chemiluminescent assay based on the detection of light emitted during H2O2 – induced oxidation of luminol [44]. The overall range of effective H2O2 inhibition was found to be 23.5 – 98.0% (425 M > 4FBCO > 4FCO > 33FMCO > 3FCO > 43FMCO > 4PP ≥ 3PP). The positive control ascorbic acid exhibited 40.4% quenching of CL at the same concentration as the all compounds (0.5 mM) except for 425 M compound which was the most effective derivative, providing 98% inhibition at concentration of 0.1 mM. Compounds 425 M, 4FBCO were more effective than ascorbic acid. The structure of these two piperazinyl flavone compounds have a methylene bridge between piperazine ring and benzoyl group. In this reaction O2¯ plays a key role in the generation of electronically excited 3- aminophthalate of an emitter of the light emission observed at 426 nm [29]. The efficiency of the antioxidant action relies on the rapidity of the O2¯ removing from the reaction mixture followed by the decreased formation of the CL emitter. By comparing Fig. 2 with Fig. 1, we assume the same hierarchic order of antioxidant potency. The results from the H2O2/luminol assay show, once again, the importance of a number of methoxy groups and the 4′ substitution for the antioxidant activity of SPF compounds. The ability of SPF compounds to scavenge the HO radical was studied by ESR spectrometry using DMPO as the spin trap. This is the routinely applied technique for monitoring the short – lived oxygen free radicals. The rate constant for reaction of HO%, formed in the Fenton reaction using ethanol as the solvent, with DMPO spin trap is very high (2.1 × 109 M−1s−1) [30]. The radical trapped by DMPO gives a spin – adduct DMPO-OH which exhibits a characteristic ESR spectrum containing four – splitted lines with an intensity ratio 1:2:2:1 and a hyperfine – splitting constant of aN =aN = 14.9 G , as shown in Fig. 2. The
The self reaction of HO2· leads to the 1O2 formation [42]
Superoxide radical interaction of the synthesized compounds was assessed using CL accompanying oxidation of the radical in DMSO due to their solubility in this solvent. All determinations are carried out in triplicate, and the results are expressed as enhancing ratio of CL sum detected from the O2¯ /DMSO system in the presence of SPF compounds. The obtained results are shown in Fig. 1. All the tested compounds showed a strong significant (p < 0.001) 2.4 – 17.2 – fold increase in the CL sum at concentration of 0.1 mM being a dose – dependent. Among considered structures, compounds (425 M, 4FBCO, 4PP and 3PP) bearing two methoxy groups, fluorine atom or methylenedioxy substituents were the most efficient as enhancers of light emission. The results seem to be largely affected by the number of methoxy
Fig. 1. Effect of piperazinyl flavone derivatives on the chemiluminescence recorded from the superoxide anion radical/DMSO reaction. Chemiluminescence sums were measured as explained under Materials and Methods. Data are shown as mean ± S.D. (n = 3). Denotations of the compounds are shown in Table 1. 6
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The ABTS+% scavenging is a widely used an antioxidant capacity assay classified as an electron – transfer based assay (TAS) [51]. The radical cation scavenging activity of the test compounds, measured by using the Randox test, is listed in Table 2. The data are presented as µM of trolox per 1 g of a sample to compare the reactivity of the synthesized compounds with the standard scavengers, ascorbic acid and BHT. Previously we found that some antibiotics belonging to penicillin [52] and tetracyclin [53] groups exhibited antioxidant activity in different in vitro assays. In view of these facts it seemed interesting to compare the antioxidant properties of SPF compounds with those of dicloxacillin and doxycycline as well as the herbal tea infusions Menthae piperitae and Cistus incanus known with their antioxidant ability. Antioxidant capacity of the test compounds as measured by the ABTS+% method followed the order: Ascorbic acid > Cistus incanus > Menthae piperitea > BHT > Doxycycline > 425 M > 4PP > 3PP > 4FBCO > 43FMCO > 4FCO > 3FCO > Dicloxacillin > 33FMCO. The synthesized compounds showed considerable less antiradical capacity than the positive controls, medicinal plants, and doxycycline. Although, the majority of the synthesized compounds were significantly stronger than dicloxacillin. The experiment provided confirmation of our earlier findings [25] about an importance of OCH3 group and fluorine atom present in the substituent R (Table 1) for the antioxidant property. Both the groups can donate an electron to free radicals [54]. The low TAS values observed for SPF compounds suggest an electron donor mechanism of antioxidant activity. Ferric ion reducing antioxidant capacity of the synthesized compounds was evaluated in the TAC assay based on the Fe(III) to Fe(II) reduction [34]. The assay uses antioxidants as Fe(III) ion reductants. It has been reported that the ferric reducing potency is correlated with a compound electron - donating antioxidant power [55]. This ability was monitored using transformation of the ferric – ferrozine complex to a ferrous/ferrozine form by measuring the change in the absorption at 562 nm. The method is simple, convenient and able to measure the total antioxidant capacity of pure substances and plant infusions [34]. The TAC values for the tested compounds were expressed in the units of µM TE/g (Table 2). These values for SPF compounds ranged from 10.8 µM TE/g to 49.5 µM TE/g, showing little Fe(III) reducing ability; they were only higher than that detected for dicloxacillin (TAC = 9.73 ± 0.8) and much more lower than those measured for ascorbic acid, BHT, doxycycline, and medicinal plant infusions, under the same reaction conditions. The total antioxidant status of the synthesized compounds evaluated by ABTS radical scavenging activity was highly correlated with that determined using the Fe(III) → Fe(II) transformation assay (r = 0.89069, p < 0.003). This finding confirms that the single – electron transfer is the main mechanism through which the synthesized compounds may express their antioxidant potential. The synthesized compounds in this paper become distinct by substitute of benzene ring of the R substituent in piperazine ring and a linkage (3′ or 4′ positions) of piperazine to flavonoid skeleton. Therefore, the differences of their antioxidant potency are discussed correlating with the newly synthesized structures. The main structure feature responsible for the free radical scavenging and antioxidant activity is the presence of fluorine atom, methoxy group on benzoyl group, the potential electron – donating methylenedioxy substituent [43,56] and a methylene bridge beteen piperazine ring a bezoyl group. The methylene bridge provides free rotation between these two structures. In turn, stereo chemical factors linked with 3′ or 4′ position might be the cause for the differences in antioxidant activity due to the stability of the product. The presented findings show that in the all applied methods for evaluation of antiradical and antioxidant activities, the highest activity was demonstrated by compound 425 M. It seems that this result is due to the presence of two – OCH3 groups in the agent structure. The presence of two –CH3 groups may stronger increase the electron density in benzene ring via electron – donating than the presence of one group (33FMCO, 43FMCO). The differences in the
parameters we obtained for HO% trapping are consistent with those reported by other authors [45,46]. The tested compounds displayed poor HO radical scavenging activity, ranging from 9% to 32% in comparison with cistus incanus (44.2%, data not shown). However thiourea, exhibiting a high reactivity towards HO% (~109 M−1s−1) [47], showed comparable radical scavenging activity (30%) as 425 M compound (32%). The percentage of HO%- scavenging activity shown by SPF compounds refers to the highest concentration of the synthesized compounds, due to their precipitation observed at higher concentrations. We observed that the presence of DMSO (3.5 M) in the Fenton reaction needed to dissolve a SPF compound, reduced the DMPO -%OH signal magnitude by 73%. The concentration of DMSO significantly exceeded the DMPO concentration (25 mM). In addition, its rate constant for HO% trapping (7 × 109 M−1s−1) [48] was greater than the DMPO rate constant (3.4 × 109 M−1s−1 [30]. This suggests that most of HO% was removed by DMSO. Indeed, we noticed the formation of a new spectrum similar to the DMPO -%CH3 adduct due to the CH3% derived from DMSO [48] (data not shown). Among a number of method applied to determine the antioxidant ability to trap free radicals, the DPPH method is most commonly used due to its simplicity and reliability. The DPPH free radical decrease in the presence of an antioxidant agent was monitored using ESR spectroscopy. Owing to the DPPH radical's ability to receive hydrogen or an electron from an antioxidant agent, the radical become a stable diamagnetic molecule. The scavenging effects of SPF compounds are shown in Table 2. Two positive controls, ascorbic acid and BHT are also included. Only two, 4FBCO and 425 M, of 8 synthesized compounds reduced DPPH% in a dose – dependent manner, presenting much weaker antiradical activity, ARP, than an endogenic antioxidant ascorbic acid, which presented an ARP value of 4.08 or the synthetic antioxidant BHT (ARP = 2.86). These values for the positive controls agree with those found by other authors [49,50]. The remaining tested agents provided from 13.2% to 18.2% the radical scavenging effect. Table 2 Antioxidant activity of the tested piperazinyl flavone compounds, positive controls, reference antibiotics and medicinal plants. Compound
3PP 4PP 3FCO 4FCO 33FMCO 43FMCO 4FBCO 425 M Positive controls Ascorbic acid BHT Reference antibiotcs Dicloxacillin Doxycycline Medicinal plants Menthae piperitae Cistus incanus
DPPH radical scavenging activity
[µM TE/g]
[µM TE/g]
16.0 ± 18.2 ± 13.2 ± 14.8 ± 13.7 ± 15.3 ± 0.244 0.435
2.5* 3.1* 2.4* 2.3* 3.0* 3.3* 8.2 4.6
0.122 0.217
264.5 308.6 243.2 255.1 209.6 259.4 260.4 392.1
23.8 20.8 15.2 17.5 10.8 15.0 13.5 49.5
4.08 2.86
0.49 0.70
2.04 1.43
– – –
Number of reduced DPPH.
± ± ± ± ± ± ± ±
7.7 7.9 6.7 7.1 6.1 6.9 6.5 8.2
± ± ± ± ± ± ± ±
0.3 0.4 0.3 0.3 0.5 0.5 0.6 0.5
6006 ± 196.8 1304 ± 43.2 241 ± 16.5
5009 ± 98.7 217 ± 5.3 9.73 ± 0.8
539 ± 28.3
428 ± 27.1
1341 ± 39.7 1538 ± 42.5
470 ± 27.8 876 ± 37.3
* Scavenging effect (mean%) at the highest tested concentration (1.25 mM). Time of steady state of the synthesized compounds in the DPPH assay was 30 min. ARP – antiradical power; SV – stechiometric value; TAS – total antioxidant status; TAC – total ferric reducing power; . BHT – butylated hydroxytoluene. Data are expressed as mean ± standard deviation of n = 3 determinations. Denotations of the synthesized compounds are listed in Fig. 1. 7
Bioorganic Chemistry 95 (2020) 103513
P. Berczyński, et al.
antiradical power observed among the particular assays result from multiple mechanisms and different reaction conditions, as well as from different oxidant behavior of the test compounds. It is noteworthy that the synthesized compounds showed broad spectrum of antioxidant activity in both in hydrophobic medium, H2O/DMSO, and H2O/DMSO/ C2H5OH solutions, being scavengers of ROS and DPPH and ABTS+ radicals.
[8] R.B. Kshatriya, Y.I. Shaikh, G.M. Nazeruddin, A brief review: Flavonoids as a pharmacophore, J. Appl. Chem. 4 (2015) 801–817. Available online at www. joac info. Assessed 20th December 2015. [9] M. Materska, Flavone C-glycosides from Capsicum annuum L.: relationships between antioxidant activity and lipophilicity, Eur. Food Res. Technol. 240 (2015) 549–557. [10] N. Masuoka, M. Matsuda, I. Kubo, Characterisation of the antioxidant activity of flavonoids, Food Chem. 131 (2012) 541–545. [11] C. López-Alarcón, A. Denicola, Evaluating the antioxidant capacity of natural products: a review on chemical and cellular-based assays, Anal. Chem. Acta 763 (2013) 1–10. [12] N. Jiang, A.L. Doseff, E. Grotewold, Flavones: from biosynthesis to health benefits, Plants (Basel) 5 (2016), https://doi.org/10.3390/plants5020027. [13] Y. Jiang, K.P. Rakesh, N.S. Alharbi, H.K. Vivek, H.M. Manukumar, Y.H.E. Mohammed, H-Li Qin, Radical scavenging and anti-inflammatory activities of (hetero) arylethenesulfonyl fluorides: Synthesis and structure-activity relationship (SAR) and QSAR studies, Bioorg. Chem. 89 (2019) 103015, https://doi.org/10. 1016/j.bioorg.2019.103015. [14] W.-Y. Fang, L. Ravindar, K.P. Rakesh, H.M. Manukuma, R.C.S. Shantharam, N.S. Alharbi, H.-L. Qin, Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review, Eur. J. Med. Chem. 173 (2019) 117–153. [15] C. Li, M.B. Sridhara, K.P. Rakesh, H.K. Vivek, H.M. Manukumar, C.S. Shantharam, H.-L. Qin, Multi-targeted dihydrazones as potent biotherapeutics, Bioorg. Chem. 81 (2018) 389–395. [16] C. Zhao, K.P. Rakesh, L. Ravidar, W.-Y. Fang, H.-L. Qin, Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: a critical review, Eur. J. Med. Chem. 162 (2019) 679–734. [17] M. Wang, K.P. Rakesh, J. Leng, W.-Y. Fang, L. Ravindar, D.C. Gowda, H.-L. Qin, Amino acids/peptides conjugated heterocycles: a tool for the recent development of novel therapeutic agents, Bioorg. Chem. 76 (2018) 113–129. [18] K.P. Rakesh, C.S. Shantharam, M.B. Sridhara, H.M. Manukumar, H.-L. Qin, Benzisoxazole: a privileged scaffold for medicinal chemistry, Med. Chem. Commun. 8 (2017) 2023, https://doi.org/10.1039/c7md00449d. [19] P. Meena, V. Nemaysh, M. Khatri, A. Manral, P.M. Luthra, M. Tiwari, Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer's disease, Bioorg. Med. Chem. 23 (2015) 1135–1148. [20] N. Samie, S. Muniandy, M.S. Kanthimathi, B.S. Haerian, R.E. Azudin, Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties, Sci. Rep. 2016 (2016), https://doi.org/10.1038/ srep24172. Accessed 13 May. [21] L. Andonova, D. Zheleva-Dimitrova, M. Georgieva, A. Zlatkov, Synthesis and antioxidant activity of some 1-aryl/aralkyl piperazine derivatives with xanthine moiety at N4, Biotechnol. Biotechnol. Equip. 28 (2014) 1165–1171. [22] C.S. Karthik, H.M. Manukumar, S. Sandeep, B.L. Sudarshan, S. Nagashree, L. Mallesha, K.P. Rakesh, K.R. Sanjay, P. Mallu, H.-L. Qin, Development of piperazine-1-carbothioamide chitosan silver nanoparticles (P1C-Tit*CAgNPs) as a promising anti-inflammatory candidate: a molecular docking validation, Med. Chem. Commun. (2018), https://doi.org/10.1039/c7md00628d. [23] W. Baker, Molecular rearrangement of some o-acyloxyacetophenones and the mechanism of the production of 3-acylchromones, J. Chem. Soc. 1381–1389 (1933). [24] M. Tuncbilek, R. Ertan, Synthesis of some 4-(3' or 4'-(4H-4-oxo-1-benzopyran-2-yl) phenyl)-1,4-dihydro-pyridine derivatives as potential calcium channel antagonists, Pharmazie 54 (1999) 255–259. [25] P. Berczyński, A. Kładna, I. Kruk, E. Sarı, H.N. Murat, O. Bozdağ Dündar, H.Y. Aboul-Enein, Synthesis and in vitro antioxidant activity study of some new piperazinyl flavone compounds, Luminescence (2017), https://doi.org/10.1002/ bio.3342. [26] J.S. Valentine, A.R. Miksztal, D.T. Sawyer, Methods for the study of superoxide chemistry in nonaqueous solutions, Methods Enzymol. 105 (1984) 71–81. [27] C. Walling, Fenton's reagent revisited, Acc. Chem. Res. 8 (1975) 125–131. [28] S. Goldstein, D. Meyerstein, G. Czapski, The Fenton reagents, Free Radic. Biol. Med. 15 (1993) 435–445. [29] X. Tao, W. Wang, Z. Wang, X. Cao, J. Zhu, L. Niu, X. Wu, H. Jiang, J. Shen, Development of a highly sensitive chemiluminescence enzyme immunoassay using enhanced luminol as substrate, Luminescence 29 (2014) 301–306. [30] E. Finkelstein, G.M. Rosen, E.J. Rauckman, Spin trapping of superoxide and hydroxyl radical: practical aspects, Arch. Biochem. Biophys. 200 (1980) 1–16. [31] F. Nanjo, K. Goto, R. Seto, M. Suzuki, M. Sakai, Y. Hara, Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical, Free Radic Biol Med. 21 (1996) 895–902. [32] W. Brand-Williams, M.-E. Cuvelier, C. Berset, Use of a free radical method to evaluate antioxidant activity, Lebensm.-Wiss. u.-Technol. 28 (1995) 25–30. [33] N.J. Miller, C. Rice-Evans, M.J. Davies, V. Gopinathan, A. Milner, A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates, Clin. Sci. 84 (1993) 407–412. [34] K.I. Berker, K. Güçlü, B. Demirata, R. Apak, A novel antioxidant assay of ferric reducing capacity measurement using ferrozine as the colour forming complexation reagent, Anal. Methods 2 (2010) 1770–1778. [35] I. Fridovich, The biology of oxygen radicals, Science 201 (1978) 875–880. [36] J.M. McCord, E.D. Jr, Day, Superoxide-dependent production of hydroxyl radical catalyzed by iron-EDTA complex, FEBS Lett. 86 (1978) 139–142. [37] N.I. 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4. Conclusion The findings allow us to judge that the synthesized compounds have the potential as antioxidants. A series of novel piperazinyl flavone compounds was synthesized and their structure was elucidated by elementary analysis, chromatography, 1H NMR spectroscopy, and mass spectral data as response to the pharmacy industry's demand for new non – toxic providing antioxidant defense against ROS. The results agree with the assigned structures. The compounds were in vitro tested for their ability to scavenge free radicals and antioxidant activity. From the performed evaluation results that all the compounds showed weak free radicals scavenging and the ferric ion reducing potentials activities when compared to the standard controls. Compound 425 M demonstrated the highest significant inhibitory effect in all six assays used. The findings showed that difference in the chemical structure of the substituent R reflects mainly to the observed antioxidant power and scavenging of free radicals. It is apparent that the presence of methoxy groups on benzene ring of the substituent R (compound 425 M) linked with piperazine ring is essential for the antioxidant and free radical inhibiting properties. The findings allow us to judge that the synthesized compounds may be used as lead molecules for optimization of molecular structure to maximize the antioxidant potency. Declaration of Competing Interest The authors declare no conflict of interest. Acknowledgements This work was supported by Research Organization of Ankara University, Ankara, Turkey (No: 12B3336003) and keeping the research potential in frame of statutory activity of West Pomeranian University of Technology in Szczecin, Szczecin, Poland (No: 518-060123161-03/ 18). Appendix A. Supplementary material Supplementary data to this article can be found online at https:// doi.org/10.1016/j.bioorg.2019.103513. References [1] V. Valko, D. Leibfritz, J. Moncol, M.T.D. Cronin, M. Mazur, J. Telser, Free radicals and antioxidants in normal physiological functions and human disease, Int. J Biochem. Cell Biol. 39 (2007) 44–84. [2] F.S. Pala, H. Gürkan, The role of free radicals in ethiopathogenesis of diseases, Adv. Mol. Biol. 1 (2008) 1–9. [3] S. Reuter, S.C. Gupta, M.M. Chaturvedi, B.B. Aggarwal, Oxidative stress, inflammation, and cancer: how are they linked? Free Radic. Biol. Med. 49 (2010) 1603–1616. [4] M. Venza, M. Visalli, C. Beninati, G.V. De Gaetano, D. Teti, I. Venza, Cellular mechanisms of oxidative stress and action in melanoma. Oxid. Med. Cell Longev., (2015) ID 481782, https://doi.org/10.1155/2015/481782. [5] X.-F. Guo, Y.-D. Yue, F. Tang, J. Wang, X. Yao, Antioxidant properties of major flavonoids and superactions of the extract of Phyllostchys pubescens leaves, J. Food Biochem. 37 (2013) 501–509. [6] X. Li, X. Quyang, R. Cai, D. Chen, 3′,8″-Dimerization enhances the antioxidant capacity of flavonoids: evidence from acacetin and isoginkgetin, Molecules 24 (2019) 2039, https://doi.org/10.3390/molecules24112039. [7] M.S.M. Al-Saleem, L.H. Al-Wahaib, W.M. Abdel-Mageed, Y.G. Gouda, H.M. Sayed, Antioxidant flavonoids from Alhagi maurorum with hepatoprotective effect, Phcog. Mag. 15 (2019) 592–599.
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I was just wondering, what are some advantages of using Front Row to watch videos or listen to music as opposed to simply using DVD or itunes? As of right now it seems like a rather pointless program to me. I have used it to watch a movie trailer, but that is about it. I didn't know if there were any features that Front Row has that the other programs did not.
— matt


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This Community respects PraetorianJDC's consistent contribution
Provided the K2K Community with its own ARK Scorched Earth Server
We have a mature, comical, dedicated group of interested individuals invested in maximizing the potential and exploration of Ark Scorched Earth. An early morning (10AM-2PMEST) group and a (4:30PM-9PMEST) group that play on this server, showing love and building and surviving within the vast lands of this new expansion and NOW- it is available for EVERYONE who supports K2K!
Question: How do I join? Answer: Follow this Guide!
Step: 1
Click on View, then Servers where it's highlighted above at the Steam Main Hub Menu
Step: 2
Click on Add Server as highlighted, type in the IP Address as listed above or copy and paste from here
and then click the highlighted button "Add This Address to Favorites"
and Viola, Click on Connect and it'll automatically connect you to the server but here's some added piece of information for ya!
Step 3: Optional Convenience
Once you've connected to the server, created a survivor, search for the server ingame by using the "My Survivors" Filter tab highlighted on the bottom right of the screen.
You'll see the K2K Community ARK Server Server pop-up. From there, you can add it to your favorites in-game and from this point forward. You can join the server
at any time from the ingame menu by searching both "My Favorites" or "My Survivors" Tab
Question 2: Whats the Password? Answer: Starcraft
Why wouldn't it be? Now Join us Gents & Ladies! Have Fun and Make the best of The ARK Experience!
and if you see Prae, remind him he's appreciated!


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Passwords are an Open Door: Lock it Down with Multi-Factor Authentication
Popular password management service LastPass is back in the news with their acquisition by LogMeIn. This summer, their headlines weren't so positive: they announced in June that 7 million user email addresses and encrypted master passwords had been compromised in a breach. It is a recurring nightmare for cyber security companies and security-minded users alike: the company you are relying on to keep your personal data safe has been hacked and your intimate information sold to the highest bidder. Fortunately, it appears that LastPass identified and contained the attack in time to warn users to change their master passwords before hackers had enough time to break the extremely strong encryption that protects the user vaults that store customers' multiple log ins.
At the time of the breach announcement, LastPass wisely advised users to set up two-factor authentication, underscoring the oft-ignored reality that passwords on their own are inherently insecure, more so everyday as the cybercrime frenzy continues unabated. Cyber attacks frequently target large user credential databases—Adobe in 2013, EBay in 2014, Anthem in 2015, and many more, the prime reason being the keys they store: These keys are the login credentials to other accounts that contain PII, sensitive personal information, financial data and/or health records, amongst many other forms of data. So by gaining access to ones credential store it is like that of gaining access to a skeleton key that opens the door for the hacker to all your other data stores at the pharmacy, at the doctors office, at the bank, at the grocery store, at the gym and so on.
A database full of personally identifiable information (PII) like names, email addresses, credit card accounts, and Social Security numbers is a lucrative target for all kinds of cybercriminals. Access to such databases should be closely guarded and strongly authenticated, but it is shocking how often this isn't the case. In the Anthem case, not only was the database itself unencrypted, it's been suggested the administrators' access credentials were far too easy to crack. Not only can the stolen PII be sold online to identity thieves, stolen credentials can also be used to gain access to other targets: bank accounts, privileged networks, confidential records, mobile devices, critical infrastructure. No one is immune: cybercriminals go after individuals, small businesses, enterprises, and governments for nefarious reasons including espionage, blackmail, terrorism, IP theft, and good old-fashioned larceny.
If even the professional password protectors can be hacked, how do we safeguard our valuable personal and business information? The answer is, just as LastPass advised, multi-factor authentication. It isn't a popular solution, but it is garnering more serious consideration and wider adoption as threats escalate and implementations improve. LastPass users may have thought they could bypass the secondary authentication option, believing their passwords were safe once encrypted. However, encryption can be decrypted, and hackers continuously develop more advanced tools to efficiently break through hashing and salting protections and crack strong passwords.
In multifactor authentication, a second method of proving your identity is required in addition to a password or PIN. This makes it much less likely that a stolen password can be used to gain illicit access to protected information or resources through applications, operating systems, mobile devices, and online services. An authentication factor is one or more of the following: what you know (a password), what you have (a smartphone, token, or striped/chipped card), and what you are (fingerprint, retina scan, or other biometric). GPS location and time-stamped factors can also be used as authentication factors in relevant scenarios that provide a fourth kind of MFA (what you are on). The strongest MFA implementations require a factor from each at least three of these categories, but adding even one object, token, or biometric requirement to a password log-in greatly increases security. The best of these solutions account for human behavior and streamline the log in process as much as possible and detect when there are deviations from this norm and enforce additional checks such as sending a one-time security token to your cell phone or registered email address or with a security question.
We are impatient creatures who aren't in the habit of being deliberate when we are jumping onto our devices and networks to work, communicate, and play. We also can't remember 15-20 different strong passwords (essentially long strings of nonsense letters, numbers, and characters) for all our accounts and services. Even when we use a harder-to-crack password (most people don't), we tend to re-use it multiple times, not change it often enough, or write it down on a sticky note attached to our laptop. We make it too easy for hackers. Organized cyber criminals are now compiling and correlating records from multiple breaches to enhance the PII data's value and exploitability for multiple targets. As a result, with each breach what follows is a significant escalation in phishing attacks as hackers use databases of stolen email addresses and accompanying personal details to send alarmingly deceptive email inquiries containing malicious links or tricking recipients into handing over even more information. In a way, by being less cautious we make the hackers job that much easier.
Widespread adoption of MFA can be seen as a type of vaccination program, increasing "herd immunity" to cyber attacks. If a huge batch of passwords is stolen, the remaining factors continue to protect PII and other valuable data, buying time for password resets and other remediation efforts. Phishing attempts to obtain login credentials are less effective if those credentials require multiple components, not all of which can be mistakenly handed over to (or stolen by) a bad actor. Strongly authenticated and encrypted networks and applications are not as appealing to hackers. On the other hand, as cyber security awareness becomes more widespread, any organization that openly insists on MFA and similar protections for all critical data and services (including supply chain and partnerships) may gain an edge over less conscientious competitors.
The standard of due care in cyber security is under increased scrutiny. The U.S. Court of Appeals ruled recently (FTC v. Wyndham) that the FTC does have the authority to hold companies liable for negligent cyber security practices. If it becomes accepted as common knowledge that single factor authentication (e.g., passwords only) provides little to no defense against cyber attacks, some form of MFA will be the expected standard. If a breach occurs due to lack of a strong authentication mechanism, an FTC intervention could result, adding to the lawsuits, financial costs, loss of reputation, and customer attrition that are sure to be incurred. For too long, Security in general has been seen as an afterthought when building an app, a device or a service for the consumer. But with these items being such an integral part of the fiber of our lives its time security came to the forefront and be top of mind when a new service launches or new features on your phone are released.
The responsible cyber citizens of the world are at war with the invisible criminals infiltrating all of our networked environments, which are more and more central to how we conduct our personal and business affairs. We have powerful defenses like multifactor authentication, but we aren't using them enough. As consumers, we have to insist that MFA be used to protect our valuable assets and data. The President has urgently emphasized its importance to the security of our economy and national security. As security professionals, we have an obligation to integrate and enforce the use of MFA throughout our internal systems as well as end user services. We are making it far too easy for hackers and thieves to use our own data against us.
Steve Lowing is the director of product management at Promisec.


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Hollywood Riviera
Sportsman's Club
Meeting Minutes
October 24, 2001 Membership Night
The meeting was called to order by Tom Rougeaux who also gave a 'CLUB OVERVIEW' to prospective new members in attandance.
Redondo Beach Fair: The subject of offering something other than funnal cakes (Shaved Ice, Root Beer Floats, Bottaled Water etc.) for Frontier Days next year was discussed.
Red Jung gave an update on the 'Club Shirt' order and advised
that his goal was to place the order by Nov. 15th,2001.
Red also advised that Club member Mel Yates was not feeling well and was scheduled to undergo back surgery sometime before Thanksgiving. A heartfelt "Best of Luck and Get well Soon" from all to Mel.
Peter Valaentin reported that we had a +$200.00 accounting revision to the income from the Manhattan Beach Fair bringing our revised net to $6,567.88 .
Tom Rougeaux stated that the Clubs facility lease renewal was being finalized and the new terms would most likely be for another two years and would call for the relocation of the storage shed.
A Sportsman's welcome to Lee Goldblott, guest of Chris Collignon.
Special Thanks to Lee Gustafson and his team for all the hard work they put in to making the Membership Dinner Meeting DELICIOUS!
Meeting adjourned.
Attendance: Barrington, Brettnacher, Collignon, Dracoules, Fernandez, Giannioses,Gustafson, Hill,Jung, Kauls, Martelaro, Ortiz, Parker, Reasor, Rougeaux, Sawyer, Seelig, Solamon, Stemmler, Stott, Valentin, Wisser GUESTS: Goldblatt
November 14, 2001
The meeting was called to order and lead by Jon Stott in Tom Rougeaux absents.
Jon Stott reminded every one to RSVP the Christmas Dinner Party and get their checks to Geoff Graue by Dec.7, 2001.
Red Jung reported that The FINAL shirt order was all set to
go and promised new shirts for the Holidays.
A motion was made and passed to order 50 new hats with the shirt order.
Red also mentioned that Mel Yates back operation was a success!
Philanthropic Committee Chairman, Allan Watt, advised that
the board had accepted the committees budget recommendations.
A motion was made and passed to approve this years Philanthropic Budget.
George Zittler will be organizing our spring golf outing which will take place on a WEEKEND in April at River Ridge Golf Club in Oxnard. Overnight accommodations will be at the Marriott Residence Inn located next to the course. For more information and reservations, please contact George.
Meeting adjourned.
Attendance: Barrington, Chandler, Collignon, Jung, Kemp, Kropp, Marousek, Martelaro, Montelongo, Musick, Parker, P. Perez, Sawyer, Stemmler, Stott, Virobik, Watt, Zettler GUESTS: Goldblatt
November 28, 2001
The meeting was called to order and lead by Jon Stott.
Jon again reminded everyone to please RSVP and get their checks into Geoff Graue for the Christmas Dinner Party.
City Government Night has been rescheduled from 2-27-2002 to 3-27-2002 and Steak and Joke Night will now be held on 2-27-2002.
A motion was made and passed to again help sponsor the South High Girls Softball Team.
A plea was again made for members who had not yet paid their dues to please do so while we are all still young!
In his absents, Dick Rectors was unanimously appointed to act as Chairman of next months Chili Cook-off. THANKS DICK!
Missed a few meetings lately??? Please be sure to mark your calendar and plan on attending the January 9th Regular Meeting the club is still in need of a Chairman for the Redondo Beach Fair!
Meeting adjourned.
Attendance: Barrington, Brettnacher, Carswell, Gustafson, Jung, Kropp, Martelaro, Parker, Perry, Sawyer, Stemmler, Stott
HRSC Home Page | Write Us


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In light of HMRC's Making Tax Digital (MTD) consultation response, Ed Molyneux, founder and CEO of FreeAgent, and John Stokdyk, Global Editor of AccountingWEB, discuss how accountancy practices should be preparing for the introduction of MTD.


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Fraud Prevention Solution For Banking & Finance Industry [Case Study]
08 Oct. 2019 Case Studies
The financial services industry, especially the financial institutions deal with multiple channels that handle millions of transactions per day. Amidst the growing number of online payments, fraudsters today apply sophisticated and advanced technologies. Therefore, fraud detection and prevention during the holiday season and otherwise poses a significant challenge for the banking & finance industry. To address this, organizations rely on financial fraud prevention solutions coupled with business intelligence to monitor, identify, and preempt the fraudulent activities in-time to eliminate the possible loss even before it happens.
Learn how Rishabh Software helped a Canada-based credit union bank in integrating a real-time fraud analysis mechanism with BI insights within its system to develop fraud detection capabilities, achieve operational efficiency, and monitor possible fraudulent activity patterns across channels.
Project Overview
For their core banking infrastructure solution, the customer sought help from us as their reliable technology service provider. The objective was two-fold – 1) to help develop and integrate the much required online banking fraud detection software capability into their existing system, 2) to identify the patterns of fraudulent scenarios using past transaction records to safeguard the system.
- Handle a million transactions per second with end-to-end visibility into payment applications
- Identify 'Fake' processing due to switch malware and card compromise with real-time tracking of transactions
- Discover a pattern of transactions occurring on a particular terminal with a limited window for fraud discovery
- Address a high number of unexpected fallback transactions
- Create complete transparency and traceability for unexpected transaction scenarios in a limited period
Our Solution
Our team analyzed the existing system of the retail-banking customer. Based on that, we created a lite component which was later integrated into their current payment-processing infrastructure. This component for fraud detection in banking sector would:
- Analyze the core banking transactions in real-time when the purchase is still in the process.
- Perform fraud checks instantly and ensure that the whole payment process is completed within milliseconds.
Further, we developed an adapter to connect with the core banking endpoints as well as switch gateways. Though, we ensured that the component doesn't affect the core banking functionality.
In addition to this, our team offered seamless integration of the fraud prevention system into their transaction workflow. We built an intuitive BI-powered dashboard that would provide insights on fraud analysis, user demography analysis, merchant analysis, and more. It would help them better prepare for an increasingly challenging business environment.
Business Benefits
- Improve operational efficiency by adhering to credit union security guidelines
- Enable business analyst to monitor, tweak, add or update fraud rules based on emerging patterns
- Handle large volumes of financial data in real-time
- Attract and retain more customers by allowing real-time blocking of card and online transactions based on fraud filters
- Make seamless integration with the legacy switch gateway system, core-banking solution, and the fraud detection system
- Save on costs and resources by using real-time insights to take preventive action and minimize fraudulent attacks
To conclude, Rishabh Software supported fraud detection and prevention for the banking institution by creating an essential component. Along with this, the BI mechanism will act as a whistleblower by providing early warnings through real-time monitoring of transaction activities.
The fraud prevention software for banks developed by our team helps their compliance team to learn new fraud behaviors and acquire regular insights. It is along with implementing new rules to keep the financial frauds out while enabling customers to have safe & comfortable banking experience.
Customer Profile
Canada-Based Credit-Union Bank with 20+ Years of Experience
Technology & Tools
- Apache Storm Framework
- RabbitMQ Message-Broker Software
- Java SE Platform
- Drools Business Logic Integration Platform


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We are frequently asked to include the results of a dynamic calculation within a CLM presentation in an approved email. An example of this would be a budget impact model where the HCP is able to adjust patient numbers etc.
Currently the only way we can do this is to set up a custom field and store the results as HTML which is then pulled into an approved email using a token for the field - but most of our clients do not want to use a custom field.
I'm not sure what the ideal solution would be for this but unfortunately we always end up recommending a product other than Veeva......would be great if we could do this within Veeva.


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Wednesday, March 17, 2010
Happy St. Patrick's Day!
I even bought a box of Lucky Charms for breakfast.
After the parade, shuttle services will begin transports to the bars for more drinking and live music. Later, those still standing will dine on corned beef and cabbage.
St. Paddy's day wouldn't be complete without a good luck toast:
"I've drunk to your health in company,I've drunk to your health alone, I've drunk to your health so many times, I've darn near ruined my own! Here's to me!"
11 comments:
A corned beef and cabbage lunch at the Senior Center after a morning of Dominoes is what I will be doing. No parade here but maybe there will be something on TV.
- March 17, 2010 at 1:14 AM
I'm thinking about maybe going shopping! That's way more fun for me!
- March 17, 2010 at 1:36 AM
- Dru said...
I'm so happy that the weather is going to cooperate because I'm going to watch the parade.
- March 17, 2010 at 5:59 AM
- Sheila Connolly said...
Beannacht Lá Fhéile Pádraig!
Yes, there's a corned beef with my name on it, lurking in my fridge. And a loaf of soda bread I've been saving.
- March 17, 2010 at 8:57 AM
- Lover of Books said...
Thinking bout making Soda Bread today. :) I like it plain with no raisins in it. I know I know I'm weird plus I'm out. lol
Kiddos are wearing green and I am going to pull out my green sweater and I put an orange cami underneath it. Obnoxious but my fav! If I can find my claddagh wedding jewelry I'll wear that too. :)
- March 17, 2010 at 10:43 AM
Our main celebration will to just have a nice quiet dinner at home....corned beef. I am wearing green, have my 4 leaf clover pin on, and I always have my shamrock tattoo on me!
Happy St. Patrick's Day to you!
- March 17, 2010 at 3:11 PM
- Andrea C. said...
Always corned beef on St. Patrick's day...and to our local pub Jackie O's for Irish dancing. We are actually Italian, but EVERYBODY is Irish on St. Patty's day! :)
- March 17, 2010 at 4:14 PM
St Patricks Day is trending on Twitter. I talked about it on my show from NYC http://bit.ly/939R8C
- March 17, 2010 at 4:17 PM
- Heather Webber said...
My daughter made sure to wear green to school so she wouldn't get pinched--and my son had Lucky Charms for breakfast. That's about the extent of our St. Patrick's Day festivities. My Callahan ancestors are probably rolling in their graves...
- March 17, 2010 at 8:28 PM
I'm with Heather...wore green today as did hubby but that's pretty much it. Oooh, wait...I had a donut with green shamrock sprinkles on it. That must count for something. :)
- March 17, 2010 at 9:14 PM
- Maggie Sefton said...
Hey, Deb---I'm traveling back to Colorado today. But for someone like me with an Irish-English father and a maiden name of Conlan, your town's celebration sounds right up my alley. What fun! I may be tempted to show up there sometime for the party. :)
- March 18, 2010 at 12:44 AM


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Do you live in Queens? Well then you might be interested to know that the PPNYC Action Fund endorsed Tony Avella for State Senator in District 11. He's running against incumbent Frank Padavan.
Did you know?
As one of the most entrenched elected officials in New York State, Frank Padavan has taken every opportunity to vote against women's health in his 38 years in the State Senate.
He voted against common-sense health legislation like the Women's Health and Wellness bill that ensured contraceptives would be covered by insurance plans, and that established minimum coverage requirements for mammograms in helping to detect breast cancer.
Frank Padavan was also 1 of just 4 State Senators to vote against the Clinic Access and Anti-Stalking Act, legislation that ensured women have safe access to reproductive health centers. And he voted against the Unintended Pregnancy Prevention Act, legislation that would have increased access to emergency contraception.
In stark contrast, Tony Avella voted in favor of a law requiring the New York City Department of Health make available emergency contraception at its health centers, health stations, health clinics or other health facilities, and he voted in favor of a law to ensure all New York City hospitals provide emergency contraception to rape survivors.
We'll keep you posted as election day draws closer, but in the meantime, check it out, educate yourself, and make sure you stay involved!


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Despite dropping five strokes in the second round Babirye still fancies her chances on her home course
Irene Nakalembe produced the best score in the second round to close in on day-one leader Martha Babirye as the Castle Lite Uganda Open ladies tournament raged on at the Lake Victoria Serena Golf Resort and Spa on Friday.
Nakalembe returned a two-over-par 74 to cut Babirye's six-stroke lead on day one, to one going into the decisive round of the 54-hole competition.
"It is still a real stiff competition but we thank God we have completed the second round and waiting for day-three. We struggled with the winds but I'm happy with my scores today. I wanted to improve and just did that and I'm happy with my personal score," Nakalembe said.
"I will stick to my game plan though everyone in the top five still has a chance," Nakalembe stated.
Despite dropping five strokes in the second round Babirye still fancies her chances on her home course.
"My game wasn't bad just that I couldn't putt well. I was struggling to play well and got so many bogeys in the process today because I'm also struggling with my sore knee and I couldn't play some shots well, but I still have a big chance to win this tournament," Babirye said.
"This is my home course and I still fancy my chances. I'm not under any pressure because we shall all be playing the same course and I've slowly gained experience on how to manage pressure,"
Three-time champion Tanzania's Angel Eaton is in third place eight strokes off and looks to have surrendered to the Ugandans.
"My golf is there; just the putting was disappointing on some few holes. All in all, I thank God for everything and hopefully tomorrow I will pull up my socks,"
"It is my first time to play at this international course, it is a beautiful course and I love it. The Ugandans have really improved and I'm happy for them but I will try to focus, put my head down and try to catch up tomorrow; 18 holes is still a lot," Eaton said.
Day 2
Martha Babirye (UG) 76; 79 155
Irene Nakalembe (UG) 82; 74 156
Angel Eaton (TZ) 82; 81 163
Hawa Wanyeche (TZ) 83; 84 167
Iddi Madiina (TZ) 90; 79 169
Louise Gitau (KEN) 84; 88 172
Eva Magala (UG) 86; 86 172
Peace Kabasweka (UG) 91; 82 173
Neema Olomi (TZ) 87; 88 175
Elias Vicky (TZ) 88; 89 177


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The Ultimate Northern Lights Experience in Canada
One thousand kilometers (roughly 620 miles) north of Winnipeg, a northerly port town is redefining the meaning of luxury travel. No, you will not find warm blue seas, five-star hotels, or grandiose spas. There is little extravagance or showiness here. Yet you will still uncover something extraordinary in this raw, untouched, remote, and once-in-a-lifetime adventure.
Discover the magic of Churchill, Manitoba on an eight-day itinerary with Frontiers North and witness one of the seven natural wonders of the world: the aurora borealis.