Design, synthesis and biological evaluation of (E)-3,4-dihydroxystyryl 4-acylaminophenethyl sulfone, sulfoxide derivatives as dual inhibitors of HIV-1 CCR5 and integrase

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• 作者：Yixing Sun^a ; ¹ ; Weisi Xu^b ; ¹ ; Ningning Fan^a ; Xuefeng Sun^a ; Xianling Ning^a ; Liying Ma^b ; ^{mal@chinaaids.cn} ; Junyi Liu^a ; ^c ; ^{jyliu@bjmu.edu.cn} ; Xiaowei Wang^a ; ^{xiaoweiwang@bjmu.edu.cn}
• 关键词：HIV dual inhibitors ; CCR5 receptor ; HIV integrase ; Sulfones ; Sulfoxides
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：25
• 期：3
• 页码：1076-1084
• 全文大小：1825 K
• 卷排序：25

文摘

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.