产紫青霉G59的两株突变株新产抗肿瘤活性产物研究

Antitumor metabolites produced by two Penicillium purpurogenum G59 mutants

目的阐明无活性真菌产紫青霉G59的两株抗肿瘤活性突变株2-2-3和PDN-f-2新产活性产物。方法采用与原始菌样品直接对照和活性跟踪分离的实验模式,利用液液萃取、柱层析、重结晶等方法分离纯化活性产物。利用现代波谱技术鉴定化合物结构。用MTT法测试样品对K562细胞的抑制活性。结果从2-2-3和PDN-f-2发酵物中分别分离鉴定了ergone(1)和citrinin(2)。化合物1和2抑制K562细胞的IC50分别为7.4和48.0μg/ml。结论化合物1和2均为产紫青霉产物中未见报道的G59的两株突变株新产活性产物。将无活性真菌野生株转化成活性突变株并研究其新产活性产物,将有可能成为拓展药源真菌活性菌株新资源的很好途径。

Objective To investigate the antitumor metabolites of fungal mutants 2-2-3 and PDN-f-2,the two bioactive mu-tants of Penicillium purpurogenum G59 that do not produce antitumor metabolites.Methods Bioactive metabolites newly produced by the mutants were isolated by a bioassay-guided separation procedure using liquid-liquid extraction,column chromatography and recrys-tallization methods through direct comparison with the sample from P.purpurogenum G59.The compounds obtained were identified by spectroscopic methods.The antitumor activity was assayed by the MTT method using K562 cells.Results Two bioactive metabolites 1 and 2 were isolated from the fermentation products of 2-2-3 and PDN-f-2,respectively,and identified as ergone（1）and citrinin（2）.Compounds 1 and 2 inhibited the proliferation of K562 cells with the IC50 values of 7.4 and 48.0 μg/ml,respectively.Conclusion Compounds 1 and 2 are the antitumor metabolites newly produced by the mutants 2-2-3 and PDN-f-2,respectively,and have not been found in the metabolites of P.purpurogenum so far.It is revealed from the present result that the alteration of secondary metabolism of wild-type fungal strains without bioactivity for obtaining bioactive metabolite-producing mutants may become a new route to expand the source of new fungal strains for drug screening.