【摘要】 利用自建的快速高效的次黄嘌呤一磷酸盐脱氢酶(Inosine monophosphate dehydrogenase,IMPDH)抑制剂的高通量筛选模型,筛选分离得到两个活性化合物2264 A和B,通过对其紫外、质谱、核磁等理化数据的分析确定2264 A为cyclopenol,2264 B为viridicatol。2264 A和B对IMPDH的IC50分别为69.68、11.86μmol/L;体外脾淋巴细胞增殖实验显示2264 A和B分别在322.6和65.8μmol/L浓度下可完全抑制由ConA活化的脾淋巴细胞增殖,表明2264 B在分子水平和细胞水平均表现出较好的免疫抑制活性,2264 A的活性相对较弱。更多还原

【Abstract】 Inosine monophosphate dehydrogenase(IMPDH) is an essential rate-limiting enzyme in the purine metabolic pathway,catalyzing the de novo synthesis of purine nucleotides required for lymphocyte proliferation.IMPDH has therefore been an attractive target for developing immunosuppressive drugs.This investigation was to discover new IMPDH inhibitors from metabolites of microorganism,and two active compounds 2264 A and B were isolated.2264 A and B were identified to be cyclopenol and viridicatol by their physicochemical properties,MS,13C-NMR and 1H-NMR analysis.IC50 of 2264 A and B were 69.68 μmol/L and 11.86 μmol/L to IMPDH,respectively,and they could completely inhibit the spleen lymphocytes proliferation stimulated by ConA at 322.6 μmol/L and 65.8 μmol/L in vitro.2264 A and B showed moderate inhibitory activity to IMPDH and spleen lymphocytes proliferation.更多还原