New molecular hybrids containing benzimidazole, thiazolidine-2,4-dione and 1,2,4-oxadiazole as EGFR directing cytotoxic agents

Herein, we, synthesized some new molecular hybrids (7a-o) having benzimidazole, thiazolidine-2,4dione and 1,2,4-oxadiazole scaffolds from the commercially available 1-methyl-1H-benzo [d]imidazole-2-carbaldehyde (1) using two key methodologies such as Knoevenagel condensation and Vilsmeier reagent mediated one-pot synthesis. Further, all the compounds in their mM concentration were screened for their in vitro cytotoxic activity against three human cancer cell lines which includes MCF-7, A-54 9 and HepG2. Among all, the compound 7n exhibited superior activity against all the cell lines as compared to standard drug erlotinib. Besides, the compounds 7d, 7e and 7f showed superior activity against MCF-7 and most promising activity against A-549 and HepG2 when compared with the positive control. As well, the tyrosine kinase EGFR inhibitory activity for the potent compounds 7d, 7e, 7f and 7n, revealed that the compounds 7e and 7n displayed nearly double potency as compared to the erlotinib drug. The molecular docking studies of active compounds 7d, 7e, 7f and 7n on EGFR target were also conducted and the results were found to be covenant with the corresponding IC50 values. (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

In this study, a series of new compounds with benzimidazole, thiazolidine-2,4-dione, and 1,2,4-oxadiazole scaffolds were synthesized and evaluated for their in vitro cytotoxic activity and tyrosine kinase EGFR inhibitory activity. Some compounds demonstrated superior activity with comparable or better efficacy than existing drugs.