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New Chalcone Derivatives with Pyrazole and Sulfonamide Pharmacophores as Carbonic Anhydrase Inhibitors



Compound containing sulfonamide, pyrazole and chalcone groups are
important in medicinal chemistry. They have a wide range of biological activities, including carbonic
anhydrase (CA) inhibitory activities.



Carbonic anhydrase I and II inhibitors are used for the treatment of diseases, such as
retinal and cerebral edema (CA I), epilepsy, and glaucoma (CA II). However, the currently available
drugs have some limitations or side effects. Thus, there is a need for new drug candidates to
overcome these issues. In this study, a series of compounds, (E)-4-(4-(3-aryl)-3-oxoprop-1-en-1-yl)-
3-phenyl-1H-pyrazol-1-yl) benzenesulfonamides MS4-MS10, were designed to discover new CA
inhibitors using a hybrid approach.



 Compounds MS4-MS10 were synthesized as shown in Scheme 1, and their chemical
structures were confirmed by 1H NMR, 13C NMR, and HRMS spectra. The CAs (E.C.4.2.1.1) inhibitory
effects of MS4-MS10 were tested on the hCA I and II isoenzymes using previously reported
procedures.



The CA inhibitors MS4–MS10 gave IC50 values (nM) of 27.8–87.3 towards hCA I and
24.4–54.8 towards hCA II while the IC50 values for reference drug acetazolamide were 384.2 (hCA I)
and 36.9 (hCA II). MS7 and MS9 exhibited 13.8 (hCA I) and 1.5 (hCA II) times more potent CA
inhibition than the reference compound acetazolamide, respectively.



 MS7 (Ar: 2,4,5-trimethoxy phenyl) and MS9 (Ar: 3,4-dimethoxy phenyl) were the
most promising compounds of our series with the lowest IC50 values towards hCA I and hCA II,
respectively, and can be considered for further studies.
