title: Synthesis and anti-H5N1 activity of chiral gossypol derivatives and its analogs implicated by a viral entry blocking mechanism.
abstract: A series of chiral gossypol derivatives and its analogs were synthesized and tested in vitro for their anti-H5N1 activity. Interestingly, (+)-gossypol derivatives and its analogs were more active against H5N1 than the corresponding (-)-gossypol derivatives and its analogs. Through a simple chemical modification with amino acids, less active chiral gossypol could be converted into more active derivatives, and most of chiral gossypol derivatives were more potent against H5N1 than 1-adamantylamine. With regard to the mechanism of action, chiral gossypol derivatives and its analogs might impair the virus entry step of cell infection, likely targeting to HA2 protein.
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China. Yanj502@yahoo.com.cn
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Long Long
authors.initials: LL
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.forename: Jingxiang
authors.initials: J
authors.lastname: Yang
authors.forename: Shuwen
authors.initials: S
authors.lastname: Wu
authors.forename: Po
authors.initials: P
authors.lastname: Tien
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D006072:Gossypol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006388:Hemagglutinins / Q000737:chemistry / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000378:metabolism; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000596:Amino Acids; D000998:Antiviral Agents; D006388:Hemagglutinins; D006072:Gossypol