Sun Yixing, Xu Weisi, Fan Ningning, Sun Xuefeng, Ning Xianling, Ma Liying, Liu Junyi, Wang Xiaowei
Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
State Key Laboratory of Infection Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center of Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China.
Bioorg Med Chem. 2017 Feb 1;25(3):1076-1084. doi: 10.1016/j.bmc.2016.12.035. Epub 2016 Dec 24.
Aiming at the limited effectiveness of current clinical therapeutic effect of AIDS, novel series of compounds bearing (E)-3,4-dihydroxystyryl sulfone (or sulfoxide) and anilide fragments were designed and synthesized as dual inhibitors of HIV-1 CCR5/IN. The biological results indicated that several target compounds showed inhibitory activity against HIV-1 Bal (R5) infection in TZM-bl cells. Besides targeting the chemokine receptor on the host cell surface, they also displayed binding affinities with HIV-1 integrase using the surface plasmon resonance (SPR) binding assays. Molecular docking studies have inferred the possible binding mode of target compounds against integrase. These data demonstrate that the structure of (E)-3,4-dihydroxystyryl sulfone and sulfoxide derivatives have the potential to derive potent dual inhibitors of HIV-1 Integrase and CCR5.
针对目前艾滋病临床治疗效果有限的问题，设计并合成了一系列新型化合物，这些化合物含有（E）-3,4-二羟基苯乙烯基砜（或亚砜）和酰苯胺片段，作为HIV-1 CCR5/整合酶的双重抑制剂。生物学结果表明，几种目标化合物对TZM-bl细胞中的HIV-1 Bal（R5）感染具有抑制活性。除了靶向宿主细胞表面的趋化因子受体外，它们还通过表面等离子体共振（SPR）结合试验显示出与HIV-1整合酶的结合亲和力。分子对接研究推断了目标化合物与整合酶的可能结合模式。这些数据表明，（E）-3,4-二羟基苯乙烯基砜和亚砜衍生物的结构有可能衍生出有效的HIV-1整合酶和CCR5双重抑制剂。
