Synthesis and Biological Evaluation of Novel Thiazole Analogs with Both Anti-Proliferative and Mechanistic Analyses and Molecular Docking Studies

摘要

Herein,we report the synthesis of a novel series of β-himachalene derivatives,including semicarbazones,thiosemicarbazones,and thiazoles.The structures of these compounds were elucidated by NMR,IR,and HRMS analysis methods.The in vitro antitumor activity of these compounds was evaluated by the MTT assay against four human cancer cell lines,such as fibrosarcoma(HT-1080),breast adenocarcinoma(MCF-7 and MDA-MB-231),and lung carcinoma(A-549),and the results indicated that all compounds showed moderate to significant cytotoxic activities against all cancer cell lines with IC_(50)values ranging from 7.19 0.30 to 50 μM.The mechanism of action of the most cytotoxic compounds 2b and 7b suggested that they induced apoptosis through caspase-3/7 activation,and elicited G2/M-phase arrest with the loss of mitochondrial membrane potential in HT-1080 cells.The molecular docking showed that compounds 2b and 7b activated the caspase-3 by forming a stable protein-ligand complex.