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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Rhodium(II) acetate-catalyzed stereoselective synthesis, SAR and anti-HIV activity of novel oxindoles bearing cyclopropane ring.
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Rhodium(II) acetate-catalyzed stereoselective synthesis, SAR and anti-HIV activity of novel oxindoles bearing cyclopropane ring.

机译：乙酸铑（II）催化的新型带有环丙烷环的吲哚的立体选择性合成，SAR和抗HIV活性。

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摘要

Novel oxindole derivatives bearing substituted cyclopropane ring have been designed on the basis of docking studies with HIV-1 RT using the software DS 2.5 and synthesized as probable NNRTIs against HIV-1 using rhodium(II) acetate-catalyzed stereoselective cyclopropanation reaction. The cyclopropane isomer, having trans relationship with respect to carbonyl of lactam moiety and functional group on the cyclopropane ring, was the major product in all cases along with a small amount of cis and methylene products. The trans isomers interacted well with HIV-1 RT through H-bonding with amino acids, like Lys101, Lys103, His235, Tyr318, constituting the non-nucleoside inhibitor binding pocket (NNIBP) during docking experiments. However, the compounds showed very little activity when subjected to in vitro anti-HIV-1 screening using beta-galactosidase assay (TZM-bl cells) and GFP quantification (CEM-GFP cells). The very low level of in vitro HIV inhibition, in comparison to predicted EC(50) values on the basis of computational studies, during CEM-GFP screening using AZT as positive control indicated that probably the HIV RT is not the viral target and the molecules work through some different mechanism.
机译：已使用DS 2.5软件在与HIV-1 RT的对接研究的基础上，设计了带有取代的环丙烷环的新型羟吲哚衍生物，并使用乙酸铑（II）催化的立体选择性环丙烷化反应合成了可能的针对HIV-1的NNRTI。在所有情况下，相对于内酰胺部分的羰基和环丙烷环上的官能团具有反式关系的环丙烷异构体是少量的主要产物，同时还有少量的顺式和亚甲基产物。反式异构体通过与氨基酸如Lys101，Lys103，His235，Tyr318的H-键与HIV-1 RT相互作用良好，构成了对接实验中的非核苷抑制剂结合口袋（NNIBP）。然而，当使用β-半乳糖苷酶测定法（TZM-bl细胞）和GFP定量法（CEM-GFP细胞）进行体外抗HIV-1筛选时，这些化合物的活性很小。与以计算研究为基础的预测EC（50）值相比，使用AZT作为阳性对照的CEM-GFP筛选过程中，体外HIV抑制水平非常低，这表明HIV RT可能不是病毒靶点，并且分子通过一些不同的机制来工作。

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