新型哌啶烷类似物的合成及作为有效醛糖还原酶抑制剂（ARIs）的生物评价。
Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs).
机构信息
Natural Products Laboratory, Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India.
出版信息
Eur J Med Chem. 2012 Nov;57:344-61. doi: 10.1016/j.ejmech.2012.09.014. Epub 2012 Sep 26.
Abstract
As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC(50) of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells.
摘要
作为我们从天然来源开发抗糖尿病药物努力的延续，从胡椒中分离出胡椒碱，并发现其能抑制重组人 ALR2，IC(50)为 160 μM。为了提高疗效，通过对该天然产物先导化合物的 styryl/aromatic 和杂环官能团进行修饰，合成了一系列类似物。所有衍生物均进行了 ALR2 抑制活性测试，结果表明，胡椒碱与吲哚衍生物的迈克尔加成物 3c、3e 和 2j 制备的加合物显示出很强的 ALR2 抑制活性，而其他化合物则显示出不同程度的抑制作用。活性化合物还能够防止人红细胞中山梨醇的积累。
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