目的研究黄直丝链霉菌18522代谢产物中的环二肽类细胞周期抑制剂。方法采用温敏型小鼠乳腺癌tsFT210细胞的流式细胞术模型,以细胞周期抑制活性为指标,对黄直丝链霉菌18522发酵液和菌丝体的氯仿提取物进行活性成分追踪分离;根据理化性质和光谱数据鉴定化合物的化学结构;采用流式细胞术测定化合物的细胞周期抑制活性。结果从氯仿提取物中分离得到6个环二肽类化合物,分别鉴定为环(丙-亮)[cyclo(Ala-Leu),1]、环(丙-异亮)[cyclo(Ala-Ile),2]、环(丙-缬)[cyclo(Ala-Val),3]、环(苯丙-亮)[cyclo(Phe-Leu),4]、环(丙-脯)[cyclo(Ala-Pro),5]和环(苯丙-缬)[cyclo(Phe-Val),6];流式细胞术测试结果表明,化合物1~6均显示细胞周期G0/G1期抑制活性。结论首次报道化合物1~6具有细胞周期抑制活性。
Objective To find the cell cycle inhibitors from the metabolites of Streptomyces flavoretus 18522.Methods Activity-guided isolation was performed on the chloroform extract of the fermentation broth and mycelia of Streptomyces flavoretus 18522 by using ts FT210 cells.Compounds were isolated through various chromatoghraphic methods and elucidated by spectroscopic means.The flow cytometry was used to evaluate the cell cycle inhibiting activity of the fractions and compounds.Results Six cyclic dipeptides were obtained and identified as cyclo(Ala-Leu)(1),cyclo(Ala-Ile)(2),cyclo(Ala-Val)(3),cyclo(Phe-Leu)(4),cyclo(Ala-Pro)(5) and cyclo(Phe-Val)(6).Conclusions Compounds 1-6 are reported as new cell cycle inhibitors for the first time.