CT2108A和B：新型脂肪酸合酶抑制剂作为抗真菌药物

CT2108A and B: New fatty acid synthase inhibitors as antifungal agents.

作者信息

Laakso Jodi A, Raulli Robert, McElhaney-Feser Gail E, Actor Paul, Underiner Ted L, Hotovec Brian J, Mocek Ursula, Cihlar Ronald L, Broedel Sheldon E

机构信息

Panlabs, Incorporated, 11804 North Creek Parkway South, Bothell, Washington 90811-8805, USA.

出版信息

J Nat Prod. 2003 Aug;66(8):1041-6. doi: 10.1021/np030046g.

DOI:10.1021/np030046g

PMID:12932120

Abstract

A systematic screen for new natural products that displayed antifungal activity by inhibition of fungal fatty acid synthase (FAS) led to the discovery of two new fungal metabolites, designated CT2108A (1) and CT2108B (2). The metabolites were produced by Penicillium solitum (Westling) strain CT2108 and were classified as azaphilones. The structures of these new metabolites were determined using a variety of 1D and 2D NMR experiments, including COSY, HMQC, and HMBC. The chemical conversion of CT2108A to CT2108B was effected using WCl(6). The related metabolite, patulodin (3), was also isolated from the fermentation culture of this P. solitum isolate. Both new compounds inhibited fungal FAS, and neither was found to significantly inhibit human FAS activity.

摘要

通过抑制真菌脂肪酸合酶（FAS）来筛选具有抗真菌活性的新天然产物的系统研究，导致发现了两种新的真菌代谢产物，命名为CT2108A（1）和CT2108B（2）。这些代谢产物由孤生青霉（韦斯特林）菌株CT2108产生，属于氮杂蒽酮类。使用包括COSY、HMQC和HMBC在内的各种一维和二维核磁共振实验确定了这些新代谢产物的结构。CT2108A到CT2108B的化学转化是使用WCl(6)实现的。相关代谢产物，棒曲霉素（3），也从该孤生青霉分离株的发酵培养物中分离出来。两种新化合物均抑制真菌FAS，且均未发现对人FAS活性有显著抑制作用。