{'fraction_non_alphanumeric': 0.022053756030323914, 'fraction_numerical': 0.018607856650585803, 'mean_word_length': 5.23175965665236, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Synthesis and Anticancer Activity of Benzimidazole/Benzoxazole Substituted Triazolotriazines in Hepatocellular Carcinoma.

BACKGROUND
Receptor Tyrosine Kinases (RTK) are a main family of cell surface receptors for growth factors, hormones and cytokines which are responsible for cell growth and differentiation and are considered as an important therapeutic target in cancer.


OBJECTIVE
The aim of this study was to design, synthesis and biological evaluation of benzimidazole/benzoxazole substituted triazolotriazines as new anticancer agents.


METHODS
A series of benzimidazolyl and benzoxazolyl-linked triazolotriazines 8a-e and 9a-e were synthesized as receptor tyrosine kinase inhibitors. Target compounds were evaluated in HGF-induced cell proliferation assay in A549, MCF-7, HepG2 and MDA-MB-231 cancer cells.


RESULTS
Hepatocellular carcinoma was the most sensitive cell line towards the tested compounds and 8e was the most potent one on HepG2 cells with IC50 value of 5.13µM which was near to crizotinib (HepG2 IC50 = 4.35µM) as a standard c-Met kinase inhibitor. c-Met kinase assay of 8e showed that this compound is not capable of inhibiting this enzyme and subsequently molecular docking confirmed low affinity of 8e towards c-Met active site and its possible anticancer mechanism through VEGFR-2 inhibition.


CONCLUSION
Further in silico predictions revealed that 8e can be a drug candidate with favorable pharmacokinetic properties.