Synthesis and biological evaluation of a focused library of beauveriolides.
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.
Nagai
Kenichiro
K
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.
Doi
Takayuki
T
Ohshiro
Taichi
T
Sunazuka
Toshiaki
T
Tomoda
Hiroshi
H
Takahashi
Takashi
T
Omura
Satoshi
S
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
D000596:Amino Acids; D047630:Depsipeptides; D007532:Isoleucine; C013833:beauverolides; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1; D000409:Alanine