Lead expansion and virtual screening of Indinavir derivate HIV-1 protease inhibitors using pharmacophoric - shape similarity scoring function.
Lead expansion and virtual screening of Indinavir derivate HIV-1 protease inhibitors using pharmacophoric - shape similarity scoring function.
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DOI：
10.6026/97320630004295
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发表时间：
2010-01-20
期刊：
影响因子：
1.9
通讯作者：
Dandekar T
中科院分区：
文献类型：
--
作者：
Shityakov S;Dandekar T
依地那韦(Crivaxan®)是一种有效的HIV(人类免疫缺陷病毒)蛋白酶抑制剂。这种酶在病毒复制中具有重要作用，被认为是非常有吸引力的抗逆转录病毒新药的靶点。然而，由于高度耐药的新型艾滋病毒毒株的作用变得不那么有效，这些毒株的蛋白水解酶有多种突变。为此，我们使用铅膨胀方法创建了一组新的化合物，具有新的作用方式来结合蛋白水解酶。产生了1300个与最初的HIT在化学上不同的化合物，并进行了筛选，以确定它们与蛋白酶的相互作用能力，并建立它们的QSAR性质。进一步的计算分析揭示了一种独特的化合物，它与最初的HIT具有不同的酶结合能力，并在报告中讨论了它对可能的新型蛋白酶抑制剂的作用。
Indinavir (Crivaxan®) is a potent inhibitor of the HIV (human immunodeficiency virus) protease. This enzyme has an important role in viral replication and is considered to be very attractive target for new antiretroviral drugs. However, it becomes less effective due to highly resistant new viral strains of HIV, which have multiple mutations in their proteases. For this reason, we used a lead expansion method to create a new set of compounds with a new mode of action to protease binding site. 1300 compounds chemically diverse from the initial hit were generated and screened to determine their ability to interact with protease and establish their QSAR properties. Further computational analyses revealed one unique compound with different protease binding ability from the initial hit and its role for possible new class of protease inhibitors is discussed in this report.