PTP1B抑制活性真菌F956的鉴定和代谢产物研究

摘要

目的 研究PTP1B抑制活性真菌菌株F956及其代谢产物.方法 通过形态观察及ITS序列系统发育分析鉴定活性菌株F956;对其发酵产物进行分离纯化获得单体化合物并通过综合波谱解析确定代谢产物的化学结构.对得到的化合物进行分子对接及PTP1B抑制活性评价.结果 F956鉴定为Mucor fragilis(易脆毛霉);从其代谢产物中得到2个具有PTP1B抑制活性的化合物F956-5和F956-6,其中F956-5与化合物JBIR-12相同,F956-6为JBIR-12的13位羟基甲基化衍生物,分子对接结果显示F956-6可占据PTP1B的活性位点;其对PTP1B的IC50分别为7.12和13.92μg/mL.结论 化合物F956-5(JBIR-12)和F956-6由易脆毛霉产生及其对PTP1B的抑制活性均为首次报道.%Objective To identify a filamentous strain F956 and study the activity of its metabolites.Methods The strain was identified by the cultural and morphological characteristics and phylogenetic analysis based on ITS rDNA;Active constituents were isolated and purified by various chromatographic techniques and the chemical structures were elucidated on the basis of comprehensive spectral data analysis.The inhibition of the compounds to PTP1B and molecular docking were evaluated.Results The strain F956 was identified as Mucorfragilis.Two compounds F956-5 and F956-6 were isolated from the metabolites.F956-5 was the same as compound JBIR-12.F956-6 was a new compound.Molecular docking showed F956-6 could occupy the active site of PTP1B.They exhibited significant inhibition to PTP 1B with IC50 values of 7.12 and 13.92μg/mL.Conclusion F956-5(JBIR-12) and F956-6 were isolated from Mucorfragilis firstly and reported as specific PTP1B inhibitors for the first time.