Design, synthesis, in-vitro and in-silico anticancer studies on amide derivatives of 1,3,4-oxadiazole-isoxazol-pyridine-benzimidazole

Abstract

We had designed and synthesized a series of novel amide derivatives of 1,3,4-oxadiazole-isoxazol-pyridine-benzimidazole (24a-j),and their structures were characterized for ¹HNMR, ¹³CNMR and mass spectral data. The preliminary anticancer applications of these compounds were screened towards four types of human cancer cell lines including PC3 (prostate), A549 (lung), MCF-7 (breast) and DU-145 (prostate). The assay results revealed that many of the target compounds displayed remarkable anticancer activity. Among them, the compounds 24f, 24 g, and 24 h were found to be more potent than rest of the compounds. The compound 24f displayed most promising anticancer activity against A549, PC3, DU-145, and MCF-7 cell lines with IC₅₀ values of 0.11 ± 0.07 µM, 0.26 ± 0.08 µM, 0.55 ± 0.06 µM, and 0.87 ± 0.09 µM than the standard drug, Etoposide. The compound 24 g showed better anticancer activity against PC3, A549, MCF-7, and DU-145 cell lines with IC₅₀ values of 0.98 ± 0.08 µM, 1.02 ± 0.45 µM, 1.29 ± 0.66 µM, and 1.74 ± 0.89 µM than the standard drug, Etoposide. The compound 24 h exhibited good anticancer activity against PC3, A549, and DU-145 cell lines with IC₅₀ values of 1.90 ± 0.39 µM, 2.12 ± 0.37 µM, and 1.88 ± 0.12 µM than the standard drug, Etoposide. The compound 24f exhibited more promising activity than the remaining compounds. These anticancer studies were correlated with molecular docking studies. Molecular docking studies supported the in vitro findings, revealing strong binding interactions of 24f with key residues in cancer-related proteins, highlighting its potential role in anticancer therapy. This work emphasizes the therapeutic promise of 1,3,4-oxadiazole derivatives in cancer treatment and underscores the need for further research to fully explore their efficacy and mechanisms of action.

Graphical Abstract