Chemical profiling, cytotoxic activities through apoptosis induction in human fibrosarcoma and carcinoma cells, and molecular docking of some 1,2,3-triazole-isoxazoline hybrids using the eugenol as a precursors.

In this research paper, we report the cytotoxic and apoptotic effects of 1,2,3-triazole derivatives in a unique 7a-g or hybrid form with isoxazoline 8a-g using the eugenol as a precursor in HT-1080 fibrosarcoma, MCF-7, and MDA-MB-231 breast carcinoma, and A-549 lung carcinoma. Data obtained on the cytotoxic effects have shown that hybrid compounds 8a-e induced a significant anticancer activity and are more important than the ones of 1,2,3-triazole derivatives 7a-g with IC50 ranging from 18 to 43 µM for the hybrids 8a-e and from 15 to 29 µM for mono-adducts 7a-g in all cell lines. Concerning the apoptotic study, compounds 7b and 8a can induce apoptosis in HT-1080 and A-549 cells as revealed by Annexin-V labeling and caspase-3/7 activity, also, the apoptotic effect was accompanied by cell cycle arrest at G2/M phase in the case of compounds 7b and 8a. Both compounds were evaluated in-silico through molecular docking and molecular dynamics and compound 8a is very active against Bcl-2 protein triggering apoptosis phenomenon by intrinsic pathway, therefore compound 8a is a potential candidate to inhibit the anti-apoptotic protein (Bcl-2).Communicated by Ramaswamy H. Sarma.