Synthesis and Evaluation of 3,5‐Disubstituted‐1,2,4‐Oxadiazolyl Benzamides as Potential Anti‐Breast Cancer Agents: In Vitro and In Silico Studies

Abstract

Abstract Herein, the synthesis, anti‐cancer evaluation, and in silico studies of a series of 1,2,4‐oxadiazole compounds ( 8 ‐ 15 ) are disclosed. The synthesized molecules were tested in vitro for anti‐cancer activity against MCF‐7, MDA‐MB‐231, HeLa, Ishikawa cell lines and human embryonic kidney (HEK‐293) cell lines. Among the synthesized compounds, 9 and 15 exhibited significant cytotoxicity, with IC 50 values of 7.82 μM and 6.02 μM, respectively, against MCF‐7 cell line, better than that of anti‐breast cancer drug, tamoxifen (IC 50 =11.92 μM), used as control. Significantly, both 9 and 15 exhibited very low toxicity (IC 50 >20 μM) against normal HEK‐293 cells. This suggests them as potentially effective anti‐cancer lead molecules. The in vitro anti‐cancer data was supported by in silico studies which also identified compounds 9 and 15 as potent inhibitors of the 17β‐hydroxysteroid dehydrogenase1 (17β‐HSD1) proteins, demonstrating strong interactions and stability The atom‐based QSAR model exhibited high accuracy, significant regression, and predictive reliability, aiding in understanding and optimizing biological activity. The drug‐likeness study of compounds 9 and 15 indicated favorable pharmacokinetics, with in silico toxicity predictions showing compound 15 to be non‐toxic. These findings suggest compounds 9 and 15 as potential lead molecules against breast cancer.