This study aimed to analyze the cytotoxic and apoptotic effects of isoxazoline derivatives with monoterpene scaffold 9a-e in HT-1080 fibrosarcoma, MCF-7, and MDA-MB-231 breast carcinoma, and A-549 lung carcinoma. The cytotoxic effects data revealed that compounds 9a-e generally induced significant cell growth inhibition in all cell lines, with IC50 ranging from 10 to 30 µM. However, for compounds 9c and 9e, the IC50 reached a value of 100 µM in HT-1080 cells. Compounds 9a, 9b, and 9d could induce apoptosis in HT-1080 cells as demonstrated by Annexin-V labeling and Caspase-3/7 activity. The apoptotic effect was accompanied by cell cycle arrest in the S phase. Molecular docking and molecular dynamics confirmed the empirical assay results and confirmed the stability of the complex with the inhibition of the anti-apoptotic protein, leading to cancer cell death. Overall, these data suggest that the proposed isoxazoline derivatives may be potential candidates for further investigation to evaluate their efficacy and optimal use in cancer treatment.Communicated by Ramaswamy H. Sarma.
Keywords: Isoxazoline; anticancer agents; apoptosis; carcinoma; cytotoxicity; fibrosarcoma; molecular docking.