作为线粒体复合物 I 抑制剂的 verticipyrone 类似物的合成与评价。
Synthesis and evaluation of verticipyrone analogues as mitochondrial complex I inhibitors.
机构信息
Center for BioEnergetics, The Biodesign Institute, and Department of Chemistry, Arizona State University, Tempe, AZ 85287, USA.
出版信息
Bioorg Med Chem. 2010 May 15;18(10):3481-93. doi: 10.1016/j.bmc.2010.03.070. Epub 2010 Mar 31.
Abstract
Verticipyrone has recently been isolated from the culture broth of Verticillium sp. and shown to inhibit NADH fumarate reductase, as well as NADH oxidoreductase (complex I) of the mitochondrial electron transport chain. In order to assess the structural elements in verticipyrone essential for complex I inhibitor, 15 structural analogues were prepared and analyzed for their effects on mitochondrial NADH oxidoreductase and NADH oxidase activities. Also measured were the abilities of several of the analogues to inhibit respiration as judged by a shift to glycolysis, and to inhibit the growth of several mammalian cell lines. The nature of the pyrone ring was shown to be important to potency of inhibition, as was the length and nature of substituents in the side chain of the analogues.
摘要
Verticipyrone 最近从 Verticillium sp 的培养液中分离出来，并被证明可以抑制 NADH 琥珀酸还原酶，以及线粒体电子传递链中的 NADH 氧化还原酶（复合物 I）。为了评估 verticipyrone 中对于复合物 I 抑制剂至关重要的结构元素，制备了 15 种结构类似物，并分析了它们对线粒体 NADH 氧化还原酶和 NADH 氧化酶活性的影响。还测量了几种类似物抑制呼吸的能力，判断标准是向糖酵解的转变，以及抑制几种哺乳动物细胞系的生长。吡喃酮环的性质被证明对抑制效力很重要，类似物侧链的长度和性质也是如此。
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