Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide
Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide
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DOI：
10.1021/jm0512490
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发表时间：
2006-06-01
影响因子：
7.3
通讯作者：
Silvestri, Romano
中科院分区：
文献类型：
--
作者：
Ragno, Rino;Coluccia, Antonio;Silvestri, Romano
分子模拟研究和更新的高度预测的3-D QSAR模型导致发现异常有效的吲哚芳基砜（IAS），其特征在于在吲哚-2-甲酰胺或吲哚-2-碳酰肼上存在吡咯烷-2-酮核或一些取代基。在基于MT-4和C8166细胞的抗HIV测定中，发现化合物7和9在亚纳摩尔浓度范围内具有活性。这些化合物，特别是化合物9，还对淋巴细胞中的HIV-112和HIV-AB 1原代分离株以及巨噬细胞中的HIV WT表现出优异的抑制活性。
Molecular modeling studies and an updated highly predictive 3-D QSAR model led to the discovery of exceptionally potent indolyl aryl sulfones (IASs) characterized by the presence of either a pyrrolidyn-2-one nucleus at the indole-2-carboxamide or some substituents at the indole-2-carbohydrazide. Compounds 7 and 9 were found active in the sub-nanomolar range of concentration in both MT-4 and C8166cell-based anti-HIV assays. These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages.