摘要
Aim To investigate the antitumor agents produced by marine-derived Penicillium flavidorsum SHK1-27.Methods The producing strain SHK1-27was fermented in a rotary shaker and bioactive metabolites in the fermentation broth were isolated through a bioassay-guided sepa-ration procedure.Structures of the bioactive compounds were investigated by spectroscopic meth-ods and their in vitro antitumor activities were assayed by the SRBmethod using K562 cells.Re-sults Eight anthraquinone derivatives were isolated from the fermentation broth of P.flavidor-sum SHK1-27 and were identified as nidurufin(1),averufin(2),8-O-methylaverufin(3),6,8-O-dimethylaverufin(4),versicolorin B(5),versicolorin A(6),versiconol(7)and averantin(8),re-spectively.Compounds 1-8 inhibited the proliferation of K562 cells and could be classified as strong(1 and 8 with the IC5o values of 12.6 and 27.7μmol·L"'respectively),moderate(2,5,6 and 7 with the ICso values of 72.4,91.0,98.7 and 93.4μmol·L-'respectively)and weak(3and 4 both with the same ICso value of>100μmol·L-')activity groups,respectively.The results showed some structure-activity relationships.Conclusion This is the first report of compounds 1-8 as the secondary metabolites of P.flavidorsum species,1,5 and 6 were isolated from fungal metabolites of the genus Penicillium for the first time,and 7 was found to occur in nature for the first time.The antitumor activities of compounds 1-8 on K562 cells were also reported for the first time in the present study.
目的阐明海洋来源常现青霉菌(Penicillium flavidorsum)SHK1-27代谢生产的抗肿瘤活性产物。方法用摇床发酵培养生产菌SHK1-27,通过跟踪活性,分离、纯化制备发酵物中的活性产物;根据理化性质并利用波谱技术确定化合物结构;用SRB法评价对K562细胞的抗肿瘤活性。结果从SHK1-27发酵物中分离得到8个蒽醌类化合物,并分别鉴定为nidurufin(1)、averufin(2)、8-O-methylaverufin(3)、6,8-O-dimethylaverufin(4)、versicolorin B(5)、versicolorin A(6)、ver-siconol(7)和averantin(8)。化合物1-8对K562细胞均显示出不同程度的细胞增殖抑制活性,其中,1和8的活性最强,IC50分别为12.6、27.7μmol·L^-1;2、5、6和7的活性次之,IC50分别为72.4、91.0、98.7和93.4μmol·L^-1;3和4的活性最弱,IC50均大于100μmol·L^-1。这些化合物的抗肿瘤活性与化学结构之间呈现出一定的相关性。结论化合物1-8均为首次从常现青霉菌(Penicilliumflavidorsum)代谢产物中分离得到,1、5和6系首次从青霉属真菌产物中得到,7为首次从自然界中得到。首次报道化合物1-8对K562细胞的抗肿瘤活性。
出处
《中国药物化学杂志》
CAS
CSCD
2007年第3期148-154,共7页
Chinese Journal of Medicinal Chemistry
基金
Natural Science Founds from NSFC(39825126,30171102,30472079&30572279)
National Basic Research Program of China(2006CB504100&G1998051113)
Hi-tech Research and Development Programof China(2001AA624020&2003AA624020)
Shandong Province Natural Science Foundation(Z2001C01)
Qingdao Natural Science Foundation(04-2-JZ-81)
China Ocean Mineral Resources R&D Association(DY105-2-04-02)
Cheung Kong Scholars Programof Ministry of Education of China for the Cheung Kong Scholar(CUI Cheng-bin)
