Novel chiral ferrocenylpyrazolo[1,5-a][1,4]diazepin-4-one derivatives – Synthesis, characterization and inhibition against lung cancer cells

A series of novel 2-ferrocenyl-7-hydroxy-5-phenethyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-one derivatives with optical activity (2) was synthesized in the microwave-assisted condition and characterized by means of IR, 1H NMR and mass spectroscopy, and furthermore confirmed by X-ray analysis of a representative compound (R)-2a. Preliminary biological evaluation showed that some compounds could suppress the growth of A549, H322 and H1299 lung cancer cells. Among the tested compounds, 2b–d were more effective and might perform their action through cell cycle arrest for A549 cell. Whereas these compounds inhibited growth of H1299 and H322 cells by inducing apoptosis. The anti-tumor activities of these compounds were related to the nature of substituents in benzene moiety. In addition, the results indicated also that compounds 2b–d possessed notable cytotoxicity and selectivity for A549 vs H1299 and H322 lung cancer cells.

A series of novel ferrocenyl pyrazole derivatives was synthesized. Some compounds could suppress the growth of A549, H322 and H1299 cells through cell cycle arrest or inducing apoptosis.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis of ferrocenyl pyrazole-containing chiral diazepin derivatives by microwave.
► Compounds could suppress the growth of A549, H322 and H1299 lung cancer cells.
► Compounds 2b–d might perform their action through cell cycle arrest or apoptosis.