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 mu M for the hybrids 8a-e and from 15 to 29 mu M 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.

Automated summary

This research paper reports the cytotoxic and apoptotic effects of 1,2,3-triazole derivatives and their hybrid forms with isoxazoline using different cancer cell lines. The hybrid compounds showed significant anticancer activity, surpassing the activity of the triazole derivatives. Compounds 7b and 8a were found to induce apoptosis in certain cancer cells, with compound 8a showing potential as an inhibitor of the anti-apoptotic protein Bcl-2.