海洋来源常现青霉菌SHK1-27生产的蒽醌衍生物及其抗肿瘤活性

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)、versiconol(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、27.7 μmol·L-1;2、5、6和7的活性次之,IC50分别为72.4、91.0、98.7和93.4 μmol·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(Penicillium flavidorsum)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.

Anthraquinone derivatives produced by marine-derived Penicillium flavidorsum SHK1-27 and their antitumor activities

Aim To investigate the antitumor agents produced by marine-derived Penicillium flavidorsum SHK1-27. Methods The producing strain SHK1-27 was fermented in a rotary shaker and bioactive metabolites in the fermentation broth were isolated through a bioassay-guided separation procedure. Structures of the bioactive compounds were investigated by spectroscopic methods and their in vitro antitumor activities were assayed by the SRB method using K562 cells. Results Eight anthraquinone derivatives were isolated from the fermentation broth of P. flavidorsum 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), respectively. Compounds 1 -8 inhibited the proliferation of K562 cells and could be classified as strong(1 and 8 with the IC50 values of 12.6 and 27.7 μmol· L-1 respectively), moderate(2, 5, 6 and 7 with the IC50 values of 72.4, 91.0, 98.7 and 93.4μmol· L-1 respectively)and weak(3 and 4 both with the same IC50 value of ＞ 100 μmol · L- 1 ) 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.