山梨白腐菌产生的新型ACAT抑制剂——特喷多尔斯。I. 生产、分离及生物学特性

Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. I. Production, isolation and biological properties.

作者信息

Huang X H, Tomoda H, Nishida H, Masuma R, Omura S

机构信息

Research Center for Biological Function, Kitasato Institute, Tokyo, Japan.

出版信息

J Antibiot (Tokyo). 1995 Jan;48(1):1-4. doi: 10.7164/antibiotics.48.1.

DOI:10.7164/antibiotics.48.1

PMID:7868384

Abstract

A series of new acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors termed terpendoles were isolated from the culture broth of a fungal strain FO-2546 which was proposed to belong to a new genus designated as Albophoma yamanashiensis. Among four structurally related terpendoles, terpendole C showed the most potent ACAT inhibitory activity with an IC50 value of 2.1 microM in an in vitro enzyme assay, followed by terpendoles D (IC50: 3.2 microM), A (15.1 microM) and B (26.8 microM). Evaluation of their ACAT inhibition in the cell assay using J774 macrophages indicated that terpendole D exhibited the highest specificity (cytotoxicity vs. ACAT inhibition) among microbial ACAT inhibitors we discovered so far.

摘要

从一株被认为属于新属山梨白腐菌的真菌菌株FO - 2546的培养液中分离出了一系列名为特彭多耳的新型酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂。在四种结构相关的特彭多耳中，特彭多耳C在体外酶测定中表现出最强的ACAT抑制活性，IC50值为2.1微摩尔，其次是特彭多耳D（IC50：3.2微摩尔）、A（15.1微摩尔）和B（26.8微摩尔）。使用J774巨噬细胞进行的细胞试验中对它们的ACAT抑制作用进行评估表明，特彭多耳D在我们迄今发现的微生物ACAT抑制剂中表现出最高的特异性（细胞毒性与ACAT抑制作用之比）。