Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups

Rika Obata; Toshiaki Sunazuka; Zhuorong Li; Zhiming Tian; Yoshihiro Harigaya; Noriko Tabata; Hiroshi Tomoda; Satoshi Omura

doi:10.7164/antibiotics.49.1133

Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups

Rika Obata
, Toshiaki Sunazuka
, Zhuorong Li
, Zhiming Tian
, Yoshihiro Harigaya
, Noriko Tabata
, Hiroshi Tomoda
, Satoshi Omura

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

41 Citations (Scopus)

Abstract

Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA: cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC₅₀ = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity(IC₅₀ = 19 nM) and in vivo efficacy (ED₅₀ = 10 mg/kg).

Original language	English
Pages (from-to)	1133-1148
Number of pages	16
Journal	Journal of Antibiotics
Volume	49
Issue number	11
DOIs	https://doi.org/10.7164/antibiotics.49.1133
Publication status	Published - 1996
Externally published	Yes

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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title = "Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups",

abstract = "Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA: cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity(IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).",

author = "Rika Obata and Toshiaki Sunazuka and Zhuorong Li and Zhiming Tian and Yoshihiro Harigaya and Noriko Tabata and Hiroshi Tomoda and Satoshi Omura",

year = "1996",

doi = "10.7164/antibiotics.49.1133",

language = "English",

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journal = "Journal of Antibiotics",

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T1 - Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups

AU - Obata, Rika

AU - Sunazuka, Toshiaki

AU - Li, Zhuorong

AU - Tian, Zhiming

AU - Harigaya, Yoshihiro

AU - Tabata, Noriko

AU - Tomoda, Hiroshi

AU - Omura, Satoshi

PY - 1996

Y1 - 1996

N2 - Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA: cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity(IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).

AB - Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA: cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity(IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).

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DO - 10.7164/antibiotics.49.1133

M3 - Article

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AN - SCOPUS:0029907659

SN - 0021-8820

VL - 49

SP - 1133

EP - 1148

JO - Journal of Antibiotics

JF - Journal of Antibiotics

IS - 11

ER -

Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups

Abstract

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