Synthesis of thiazolidine-2-thione derivatives and evaluation of their hepatoprotective effects.
A series of N-(mercaptoalkyl)thiazolidine-2-thiones and their derivatives were synthesized and evaluated for hepatoprotective activities against Propionibacterium acnes-lipopolysaccharide (P. acnes-LPS)-induced liver injury in mice and in vitro lipid peroxide (LPO) formation in rat liver microsomes. Reaction of N-(p-methoxybenzylthioalkyl)cysteine methyl ester (11) with 1,1'-thiocarbonyldiimidazole followed by deprotection gave the corresponding thiazolidine-2-thione derivatives. Among the compounds synthesized, 1a and 2a showed the most potent hepatoprotective activities against P. acnes-LPS-induced liver injury. Compounds 1a-f and 4 inhibited LPO formation in vitro. Compounds 1a and 2a were chosen for further pharmacological evaluations.
Yoneda
K
K
Central Research Laboratory, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Ota
A
A
Kawashima
Y
Y
D000818:Animals; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D013844:Thiazoles