New chromanone derivatives containing thiazoles: Synthesis and antitumor activity evaluation on A549 lung cancer cell line

Novel 2-[2-(chroman-4-ylidene)hydrazinyl]-4/5-substituted thiazole derivatives (2a-i) were synthesized and investigated for their anticancer activity. Cytotoxic activity on A549 and NIH/3T3 cell lines was determined, most of the compounds exhibited high cytotoxic profile with selectivity. Selected compounds 2b, 2c, 2e, 2g, 2h, and 2i were tested to determine induction of apoptosis, mitochondrial membrane depolarization, and cell cycle arrest. The results showed that the compounds induced apoptosis intrinsically that they triggered loss of mitochondrial potential through increasing the accumulation of cells in G2/M. Besides, intrinsic apoptotic pathway was supported by down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of proapoptotic protein Bax. Molecular docking study for compounds 2b, 2c, and 2g was promoted experimental outcomes.

Automated summary

The novel synthesized compounds showed high cytotoxicity against lung cancer and fibroblast cells, affecting apoptosis and cell cycle by inducing loss of mitochondrial potential and regulating protein expression.