Synthesis and anticancer activity of some 8-substituted-7-methoxy-2H-chromen-2-one derivatives toward hepatocellular carcinoma HepG2 cells

•Coumarin-pyrazoline hybrids were synthesized.•Compounds were evaluated for their anticancer activity on HepG2 human cell line.•Compounds inhibited telomerase up to 78.6%.•The most active compound, 7e, induced apoptosis in a dose dependent manner.

Based on the reported anticancer activity of coumarin and pyrazoline derivatives, the present investigation dealt with the design and synthesis of coumarin derivatives bearing diversely substituted pyrazoline moieties 7–10. The non-cyclic isosteres 11a–e of compounds 10a–e were synthesized for comparative reasons. The target compounds were synthesized from 8-acetyl-7-methoxycoumarin that underwent Claisen–Schmidt condensation with various aldehydes to give the chalcones 6a–e, followed by reaction with hydrazine hydrate, phenyl hydrazine or semicarbazide under the appropriate conditions. Cytotoxicity of the synthesized compounds was evaluated in vitro against liver HepG2 cell line. Compounds were active in the nanomolar range. The most active compounds were investigated for their telomerase inhibition and proapoptotic activities.

Graphical abstractFour series of coumarin-pyrazoline hybrids, in addition to a series of coumarins bearing non-cyclic isosteres of pyrazolines, were synthesized. Cytotoxicity against HepG2 cell line was evaluated. Telomerase inhibition and apoptosis induction were examined for the most active compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide