Synthesis and biological evaluation of a focused library of beauveriolides

Kenichiro Nagai; Takayuki Doi; Taichi Ohshiro; Toshiaki Sunazuka; Hiroshi Tomoda; Takashi Takahashi; Satoshi Omura

doi:10.1016/j.bmcl.2008.06.054

Synthesis and biological evaluation of a focused library of beauveriolides

Bioorg Med Chem Lett. 2008 Aug 1;18(15):4397-400. doi: 10.1016/j.bmcl.2008.06.054. Epub 2008 Jun 20.

Authors

Kenichiro Nagai¹, Takayuki Doi, Taichi Ohshiro, Toshiaki Sunazuka, Hiroshi Tomoda, Takashi Takahashi, Satoshi Omura

Affiliation

¹ 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.

PMID: 18620856
DOI: 10.1016/j.bmcl.2008.06.054

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alanine / chemistry
Amino Acids / chemistry
Animals
Atherosclerosis / prevention & control
Combinatorial Chemistry Techniques*
Depsipeptides / chemical synthesis*
Depsipeptides / chemistry
Depsipeptides / pharmacology*
Disease Models, Animal
Isoleucine / chemistry
Lipid Metabolism / drug effects*
Macrophages / drug effects
Mice
Molecular Structure
Sterol O-Acyltransferase / drug effects
Sterol O-Acyltransferase / metabolism*
Structure-Activity Relationship

Substances

Amino Acids
Depsipeptides
Isoleucine
beauverolides
Sterol O-Acyltransferase
sterol O-acyltransferase 1
Alanine