title: Design, synthesis and biological evaluation of small molecular polyphenols as entry inhibitors against H(5)N(1).
abstract: To find novel compounds against H5N1, three series of known or novel small molecular polyphenols were synthesized and tested in vitro for anti-H5N1 activity. In addition, the preliminary structure-antiviral activity relationships were elaborated. The results showed that some small molecular polyphenols had better anti-H5N1 activity, and could serve as novel virus entry inhibitors against H5N1, likely targeting to HA2 protein. Noticeably, compound 4a showed the strongest activity against H5N1 among these compounds, and the molecular modeling analysis also suggested that this compound might target to HA2 protein. Therefore, compound 4a is well qualified to serve as a lead compound or scaffold for the further development of H5N1 entry inhibitor.
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: Yanj502@sohu.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China; Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; School of Pharmaceutical Sciences, Hunan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Jing Xiang
authors.initials: JX
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China; Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China; Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: The College of Life Sciences, State Key Laboratory of Virology, Modern Virology Research Center, Wuhan University, Wuhan 430072, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China; Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: The College of Life Sciences, State Key Laboratory of Virology, Modern Virology Research Center, Wuhan University, Wuhan 430072, China. Electronic address: shuwenwu@hotmail.com.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Wu
authors.affiliation: The College of Life Sciences, State Key Laboratory of Virology, Modern Virology Research Center, Wuhan University, Wuhan 430072, China. Electronic address: tienpo@sun.im.ac.cn.
authors.forename: Po
authors.initials: P
authors.lastname: Tien
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D059808:Polyphenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D059808:Polyphenols; D054852:Small Molecule Libraries
keywords: Anti-H(5)N(1) activity; Entry inhibitor; HA2; Molecular modeling; Small molecular polyphenols; Synthesis