5-氮杂胞苷诱导内生真菌Penicillium sp. GZWMJZ-042代谢抗α-葡萄糖苷酶活性产物研究  

Study on theα-glucosidase inhibitors from endophytic Penicillium sp.GZWMJZ-042 induced by 5-azacytidine

作　　者：王晓洋[1,2] 龚倩玉 许言超 左明星 王立平 朱伟明 Wang Xiaoyang;Gong Qianyu;Xu Yanchao;Zuo Mingxing;Wang Liping;Zhu Weiming(State Key Laborataory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014;Natural Products Research Center of Guizhou Province,Guiyang 550014;School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003)

机构地区：[1]省部共建药用植物功效与利用国家重点实验室,贵州医科大学,贵阳550014 [2]贵州省天然产物研究中心,贵阳550014 [3]中国海洋大学医药学院,青岛266003

出　　处：《中国抗生素杂志》2023年第10期1118-1125,共8页Chinese Journal of Antibiotics

基　　金：贵州省“百人领军人才”计划;中国科学院西部青年学者(院外);贵州省基础研究(自然科学)(No.黔科合基础-ZK[2022]一般392)。

摘　　要：目的 利用表观遗传修饰剂诱导杜仲内生真菌Penicillium sp. GZWMJZ-042产生活性代谢产物。方法 在大米固体培养基中添加5-氮杂胞苷对真菌进行培养;利用柱色谱及高效液相色谱等对发酵产物进行分离、纯化;运用质谱、核磁共振和比旋光等鉴定化合物的结构;采用PNPG法测试化合物的α-葡萄糖苷酶抑制活性。结果 从菌株GZWMJZ-042的发酵产物中分离并鉴定了9个单体化合物,其中化合物1为新化合物,其结构分别鉴定为14-hydrocyclopeptin(1)、viridicatol(2)、viridicatin(3)、(2S,4a R,4b R,6a S,12b S,12c S,14a S)-4a-demethylpaspaline-4a-carboxylicacid(4)、fumigaclavineC(5)、(-)chaetominine(6)、cyclo(dehydrohistidyl-L-tryptophyl)(7)、dankasterones A(8)和2’-deoxythymidine(9)。化合物1,2,4,6~9对α-葡萄糖苷酶表现出较强的抑制作用,IC50分别为147.0、118.7、110.5、65.9、74.6、40.6和151.5μg/mL,阳性对照阿卡波糖的IC50为163.9μg/mL。结论利用表观遗传修饰剂可诱导杜仲内生真菌产生结构新颖的活性化合物。Objective To induce the production of active metabolites in endophytic fungus Penicillium sp.GZWMJZ-042 from Eucommia ulmoides using epigenetic activation strategy.Methods The fungus was fermented on rice solid medium supplemented with 5-azacytidine.The isolation and purification of compounds were performed by means of column chromatography and HPLC.Their structures were elucidated through the analysis of MS,NMR and specific rotation.The inhibitory activities againstα-glucosidase were assayed by PNPG method.Results Nine compounds(1-9)including one new compound(1)were isolated from the cultural broth of Penicillium sp.GZWMJZ-042.Their structures were identified as 14-hydrocyclopeptin(1),viridicatol(2),viridicatin(3),(2S,4aR,4bR,6aS,12bS,12cS,14aS)-4a-demethylpaspaline-4a-carboxylic acid(4),fumigaclavine C(5),(-)chaetominine(6),cyclo(dehydrohistidyl-L-tryptophyl)(7),dankasterones A(8)and 2'-deoxythymidine(9),respectively.Compounds 1,2,4,6-9 showed significant activities againstα-glucosidase with IC50 values of 147.0,118.7,110.5,65.9,74.6,40.6 and 151.5μg/mL,respectively.Acarbose,used as the positive control,had an IC50 of 163.9μg/mL.Conclusion Epigenetic modifiers can induce endophytic fungi from Eucommia ulmoides to produce bioactive compounds with novel structures.

关 键 词：内生真菌 表观遗传修饰 活性产物 Α-葡萄糖苷酶 

分 类 号：R978.1[医药卫生—药品]