title: Design, synthesis and biological evaluation of (E)-3,4-dihydroxystyryl 4-acylaminophenethyl sulfone, sulfoxide derivatives as dual inhibitors of HIV-1 CCR5 and integrase.
abstract: 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.
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Weisi
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Fan
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xianling
authors.initials: X
authors.lastname: Ning
authors.affiliation: 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. Electronic address: mal@chinaaids.cn.
authors.forename: Liying
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China. Electronic address: jyliu@bjmu.edu.cn.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: xiaoweiwang@bjmu.edu.cn.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019713:Receptors, CCR5 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013454:Sulfoxides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000813:Anilides; D019380:Anti-HIV Agents; C584933:CCR5 protein, human; D019428:HIV Integrase Inhibitors; D019713:Receptors, CCR5; D013343:Styrenes; D013450:Sulfones; D013454:Sulfoxides; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: CCR5 receptor; HIV dual inhibitors; HIV integrase; Sulfones; Sulfoxides