海洋来源真菌菌株青霉属和曲霉属中 PTP1B 抑制性次生代谢产物

PTP1B inhibitory secondary metabolites from marine-derived fungal strains Penicillium spp. and Eurotium sp.

机构信息

Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Republic of Korea, Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.

出版信息

J Microbiol Biotechnol. 2013 Sep 28;23(9):1206-11. doi: 10.4014/jmb.1303.03078.

DOI:10.4014/jmb.1303.03078

PMID:23770564

Abstract

The selective inhibition of PTP1B has been widely recognized as a potential drug target for the treatment of type 2 diabetes and obesity. In the course of screening for PTP1B inhibitory fungal metabolites, the organic extracts of several fungal species isolated from marine environments were found to exhibit significant inhibitory effects, and the bioassay-guided investigation of these extracts resulted in the isolation of fructigenine A (1), cyclopenol (2), echinulin (3), flavoglaucin (4), and viridicatol (5). The structures of these compounds were determined mainly by analysis of NMR and MS data. These compounds inhibited PTP1B activity with 50% inhibitory concentration values of 10.7, 30.0, 29.4, 13.4, and 64.0 micrometer, respectively. Furthermore, the kinetic analysis of PTP1B inhibition by compounds 1 and 5 suggested that compound 1 inhibited PTP1B activity in a noncompetitive manner, whereas compound 5 inhibited PTP1B activity in a competitive manner.

摘要

蛋白酪氨酸磷酸酶 1B（PTP1B）的选择性抑制作用已被广泛认为是治疗 2 型糖尿病和肥胖症的潜在药物靶点。在筛选具有 PTP1B 抑制活性的真菌代谢产物的过程中，从海洋环境中分离得到的几种真菌的有机提取物表现出显著的抑制活性，对这些提取物进行基于生物测定的研究导致分离得到了果糖嗪 A（1）、环丙醇（2）、表伊廷（3）、黄皮酰胺（4）和堇菜色醇（5）。这些化合物的结构主要通过 NMR 和 MS 数据分析确定。这些化合物对 PTP1B 活性的抑制作用的 50%抑制浓度值分别为 10.7、30.0、29.4、13.4 和 64.0 微米。此外，化合物 1 和 5 对 PTP1B 抑制的动力学分析表明，化合物 1 以非竞争性方式抑制 PTP1B 活性，而化合物 5 以竞争性方式抑制 PTP1B 活性。