Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via A. De Gasperi 2, 53100 Siena, Italy.
ChemMedChem. 2011 Feb 7;6(2):343-52. doi: 10.1002/cmdc.201000510. Epub 2011 Jan 18.
As a continuation of our previous work, which resulted in the identification of a new hit compound as an HIV-1 integrase inhibitor, three novel series of salicylic acid derivatives were synthesized using three versatile and practical synthetic strategies and were assayed for their capacity to inhibit the catalytic activity of HIV-1 integrase. Biological evaluations revealed that some of the synthesized compounds possess good inhibitory potency in enzymatic assays and are able to inhibit viral replication in MT-4 cells at low micromolar concentrations. Finally, docking studies were conducted to analyze the binding mode of the synthesized compounds within the DNA binding site of integrase in order to refine their structure-activity relationships.
作为我们之前工作的延续，我们已经鉴定出一种新的先导化合物作为 HIV-1 整合酶抑制剂。在此基础上，我们使用三种灵活实用的合成策略，合成了三个新型水杨酸衍生物系列，并对它们抑制 HIV-1 整合酶催化活性的能力进行了检测。生物评价结果表明，部分合成化合物在酶促实验中具有良好的抑制活性，并且能够在低微摩尔浓度下抑制 MT-4 细胞中的病毒复制。最后，我们进行了对接研究，以分析合成化合物在整合酶 DNA 结合位点中的结合模式，从而进一步优化它们的构效关系。
