Search for inhibitors of NADH-fumarate reductase from second metabolites of bacteria, actinomycetes and fungi

使用约8，200份真菌、放线菌和细菌培养液样品筛选NADH-延胡索酸还原酶抑制剂。约2%的肉汤抑制酶。大部分中试样品中含有的活性成分均为生物碱。富马酸或小分子有机化合物或无机盐显示抑制活性。另一方面，在撞击样品中发现两种疏水活性化合物。一种是从链霉菌发酵液中分离得到的（4 E）-5-（2-甲基苯基）-4-戊烯酸，这是第一个由放线菌产生的NADH-延胡索酸还原酶抑制剂。另一个是从青霉FKI-5329发酵液中分离得到的五烯类化合物prugoesterone A1和两个新的类似物。它们对NADH-延胡索酸还原酶表现出很强的抑制活性。

Screening for inhibitors of NADH-fumarate reductase was conducted using about 8,200 samples of cultured broths of fungi, actinomycetes and bacteria. About 2% of the broths inhibited the enzyme. Active components containing in most of the hit samples were hydrophillic. Fumaric acid or small organic compounds or inorganic salts showed the inhibitory activity was suggested. On the other hand, two hydrophobic active compounds were found in the hit samples. One was (4E)-5-(2-methylphenyl)-4-pentenoic acid from a broth of Streptomyces sp. This was the first NADH-fumarate reductase inhibitor produced by actinomycetes. Anothers were pentaene compounds, prugosene A1 and two new analogs isolated from cultured broth of Penicillium sp FKI-5329. They showed strong inhibitory activity against NADH-fumarate reductase.