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 journalArticle

36 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 languageEnglish
Pages (from-to)1133-1148
Number of pages16
JournalJournal of Antibiotics
Volume49
Issue number11
Publication statusPublished - 1996
Externally publishedYes

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Structure-Activity Relationship
Hydroxyl Radical
Sterol O-Acyltransferase
Inhibitory Concentration 50
Cholesterol
Cricetinae
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Obata, R., Sunazuka, T., Li, Z., Tian, Z., Harigaya, Y., Tabata, N., ... Omura, S. (1996). Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups. Journal of Antibiotics, 49(11), 1133-1148.

Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups. / Obata, Rika; Sunazuka, Toshiaki; Li, Zhuorong; Tian, Zhiming; Harigaya, Yoshihiro; Tabata, Noriko; Tomoda, Hiroshi; Omura, Satoshi.

In: Journal of Antibiotics, Vol. 49, No. 11, 1996, p. 1133-1148.

Research output: Contribution to journalArticle

Obata, R, Sunazuka, T, Li, Z, Tian, Z, Harigaya, Y, Tabata, N, Tomoda, H & Omura, S 1996, 'Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups', Journal of Antibiotics, vol. 49, no. 11, pp. 1133-1148.
Obata, Rika ; Sunazuka, Toshiaki ; Li, Zhuorong ; Tian, Zhiming ; Harigaya, Yoshihiro ; Tabata, Noriko ; Tomoda, Hiroshi ; Omura, Satoshi. / Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups. In: Journal of Antibiotics. 1996 ; Vol. 49, No. 11. pp. 1133-1148.
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AU - Tomoda, Hiroshi

AU - Omura, Satoshi

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