Synthesis and anticancer activity of 2-alkylaminomethyl-5-diaryl- methylenecyclopentanone hydrochlorides and related compounds

Eleven new diaryl-methylenecyclopentanone Mannich hydrochlorides and related compounds were synthesized with different modification on Mannich base and α,β-unsaturated bonds. The glutathione-binding ability, glutathione-s-transferase π (GSTπ) inhibition and antitumor effect of these compounds were compared. Compounds containing both Mannich base and α-unsaturated bond have GSH binding ability, GSTπ inhibitory activity and antitumor effect. Compounds without Mannich base or having a α-saturated bond lose GSH binding ability and the antitumor effect. Converting of Mannich base from dimethylaminomethyl group to morpholino, pyrrolidino, or piperidino-methyl groups do not evidently change the antitumor effect. However replacement of phenyl group with methylphenyl group on β-chain significantly increases cytotoxic effect in breast cancer cells but not in immortalized mammary epithelial cells. Our data suggest that diaryl-methylenecyclopentanones represent a new category of compounds which might inhibit tumor growth through binding to glutathione or thiol proteins.