红海榄共生真菌Penicillium sp.HK13-8细胞毒活性成分研究  

Cytotoxic metabolites from symbiotic fungus Penicillium sp.HK13-8 with Rhizophora stylosa

作　　者：韩秀丽[1] 林贞健[1] 陶洪文[1] 刘培培[1] 王乂[1] 朱伟明[1] 

机构地区：[1]海洋药物教育部重点实验室中国海洋大学医药学院,山东青岛266003

出　　处：《中国海洋药物》2009年第5期11-16,共6页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金课题(No.30670219);863课题(2007AA09Z447;2007AA091502)资助项目

摘　　要：为了从红树植物共生真菌中获得抗肿瘤药物先导化合物,采用集成化学与细胞毒活性的筛选方法,从红海榄(Rhizophora stylosa Griff.)的共生真菌中筛选获得1株对小鼠白血病细胞株P388具有细胞毒活性的菌株Penicillium sp.HK13-8。采用色谱和波谱方法,从其发酵产物中分离鉴定了5个化合物:S-弯孢霉素(1)、(22E,24R)-3β,5α,9α-三羟基-7,22麦角甾二烯-6-酮(2)、麦角甾醇(3)、胸腺嘧啶(4)和尿嘧啶(5)。S-弯孢霉素对人早幼粒白血病细胞HL-60具有较强的增殖抑制作用(IC_(50)值为2.56μM),其含量约占总产量的40%,是Penicillium sp.HK13-8的主要活性产物。To search for structurally novel and biologically active compounds from mangrove symbiotic fungi, a fungal strain HK13-8 identified as Penicillium sp. was obtained by integrated cytotoxic and chemical screening methods from the mangrove plant, Rhizophora stylosa Griff. The EtOAc extract of the fermentation broth of Penicilliurn sp. HK13-8 showed obvious cytotoxicity against P388 cells, and showed pink and yellow spots on TLC plates after spraying with Legal reagent and 10% FeCl3 solution, respectively. Through bioassay-guided fractionation, 5 compounds were isolated. By means of spectroscopic methods including 1D-, 2D-NMR, MS, and specific rotation, their structures were identified as S- curvularin （1, 40 % yield）, （ 22E, 24R）-313, 5a, 9α-trihydroxyergosta-7,22-dien-6-one （2）, ergosterol （3）, thymine （4） and uracil （$）, respectively. S-curvularin that exhibited moderate cytotoxicity against HL-60 cells with an IC50 value of 2.56μM was the main active metabolite of Penicillium sp. HK13 8.

关 键 词：红海榄 共生真菌 弯孢霉素 细胞毒性 

分 类 号：R915.1[医药卫生—微生物与生化药学] R96[医药卫生—药学]