title: Synthesis and biological evaluation of a focused library of beauveriolides.
abstract: Fungal beauveriolide III (1b), discovered as an inhibitor of lipid droplet accumulation in mouse macrophages and showing antiatherogenic activity in mouse model, consists of l-Phe, l-Ala, d-allo-Ile, and (3S, 4S)-3-hydroxy-4-methyloctanoic acid moieties. A combinatorial library of beauveriolide analogues focusing on l-Ala and d-allo-Ile of 1b was synthesized by combinatorial synthesis. Among them, d-Ala analogues consisting of A{2} improved their solubility, while those with 7{1,3,2},7{2,3,1}, and 7{2,3,2} were 20 times more potent than 1b.
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University and The Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nagai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
authors.forename: Taichi
authors.initials: T
authors.lastname: Ohshiro
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
mesh_terms: D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control; D020650:Combinatorial Chemistry Techniques; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D007532:Isoleucine / Q000737:chemistry; D050356:Lipid Metabolism / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D002785:Sterol O-Acyltransferase / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D047630:Depsipeptides; D007532:Isoleucine; C013833:beauverolides; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1; D000409:Alanine