title: Synthesis and evaluation of a difluoromethylene analogue of sphingomyelin as an inhibitor of sphingomyelinase.
abstract: A sphingomyelin analogue 2, in which the long alkenyl chain and the phosphodiester moiety of sphingomyelin were replaced by a phenyl and an isosteric difluoromethylenephosphonic acid, was prepared to evaluate its inhibitory potency to sphingomyelinase. The analogue non-competitively inhibited the neutral sphingomyelinase in bovine brain microsomes with an IC50 of 400 microM. The compound had the ability to suppress tumor necrosis factor alpha-induced apoptosis of PC-12 neurons at a low concentration of 0.1 microM.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy & Life Science, Hachioji, Japan. yokomatu@ps.toyaku.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Yokomatsu
authors.forename: H
authors.initials: H
authors.lastname: Takechi
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
authors.forename: S
authors.initials: S
authors.lastname: Shibuya
authors.forename: T
authors.initials: T
authors.lastname: Kominato
authors.forename: S
authors.initials: S
authors.lastname: Soeda
authors.forename: H
authors.initials: H
authors.lastname: Shimeno
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008861:Microsomes / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D013109:Sphingomyelins / Q000138:chemical synthesis* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D063065:Organophosphonates; D013109:Sphingomyelins; D014409:Tumor Necrosis Factor-alpha; D013108:Sphingomyelin Phosphodiesterase