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

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

PHA - Molecular Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

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.

Original language	English
Pages (from-to)	4397-4400
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2008.06.054
Publication status	Published - 2008 Aug 1

Keywords

ACAT
Antiatherogenic activity
Cyclic depsipeptide
Focused library

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10.1016/j.bmcl.2008.06.054

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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.",

keywords = "ACAT, Antiatherogenic activity, Cyclic depsipeptide, Focused library",

author = "Kenichiro Nagai and Takayuki Doi and Taichi Ohshiro and Toshiaki Sunazuka and Hiroshi Tomoda and Takashi Takahashi and Satoshi Omura",

note = "Funding Information: This work was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), by grant-in-aid for Scientific Research (B) 18390008 (H.T.) and Scientific Research on Priority Areas 18032028 (T.D.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by the Hoh-ansya Foundation, Japan.",

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doi = "10.1016/j.bmcl.2008.06.054",

language = "English",

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AU - Nagai, Kenichiro

AU - Doi, Takayuki

AU - Ohshiro, Taichi

AU - Sunazuka, Toshiaki

AU - Tomoda, Hiroshi

AU - Takahashi, Takashi

AU - Omura, Satoshi

N1 - Funding Information: This work was supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), by grant-in-aid for Scientific Research (B) 18390008 (H.T.) and Scientific Research on Priority Areas 18032028 (T.D.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by the Hoh-ansya Foundation, Japan.

PY - 2008/8/1

Y1 - 2008/8/1

N2 - 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.

AB - 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.

KW - ACAT

KW - Antiatherogenic activity

KW - Cyclic depsipeptide

KW - Focused library

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Synthesis and biological evaluation of a focused library of beauveriolides

Abstract

Keywords

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