Ramachary-Bressy-Wang [3+2]cycloaddition reaction: Synthesis of fully decorated 1,2,3-triazoles as potent anticancer and EGFR inhibitors

A general strategy was developed for the synthesis of new fully decorated 1,2,3-triazoles (5a-m & 6a-e) containing coumarine and sulfonyl-benzimidazole from 3-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)sulfonyl)acetyl)-2H-chromen-2-one and several azides using Ramachary-Bressy-Wang organocatalytic cycloaddition method. In vitro anticancer activity of all these derivatives revealed that five compounds like 5f, 5j, 5k, 5l and 5m were active against three human cancer cell lines like breast carcinoma (MCF-7), cervical carcinoma (HeLa) and alveolar carcinoma (A-549). In specific, compounds 5k and 5m showed superior activity against MCF-7 and HeLa cell lines than the standard drugs Doxorubicin and Erlotinib. Later, the results of inhibitory assay of potent compounds 5f, 5j, 5k, 5l and 5m against the tyrosine kinase EGFR revealed that compounds 5k and 5m showed nearly double the potency of the reference drug erlotinib. The in silico studies of five potent compounds 5f, 5j, 5k, 5l and 5m were also carried out to identify the interactions against EGFR receptor and found that the energy calculations were covenant with the obtained IC50 values. Finally, in silico pharmacokinetic profile was predicted for five potent compounds using SWISS/ADME and pkCSM, where all the five compounds followed Lipinski and Veber rule without any deviation. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study developed a strategy for the synthesis of new fully decorated 1,2,3-triazoles containing coumarin and sulfonyl-benzimidazole, and demonstrated their potential anticancer activity against various human cancer cell lines. Specifically, two compounds showed superior activity compared to standard drugs, and further experiments revealed their potency against the tyrosine kinase EGFR. In silico studies also provided valuable insights into the interactions and pharmacokinetic profiles of these compounds.