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 alpha,beta-unsaturated bonds. The glutathione-binding ability, glutathione-s-transferase pi (GSTpi) inhibition and antitumor effect of these compounds were compared. Compounds containing both Mannich base and alpha-unsaturated bond have GSH binding ability, GSTpi inhibitory activity and antitumor effect. Compounds without Mannich base or having a alpha-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 beta-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.
Wang
Jingli
J
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110015, China.
Zhao
Linxiang
L
Wang
Rui
R
Lu
Min
M
Chen
Duo
D
Jing
Yongkui
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
D000970:Antineoplastic Agents; D003517:Cyclopentanes; C007201:cyclopentanone; D005982:Glutathione Transferase; D005978:Glutathione