Synthesis and anti-H5N1 activity of chiral gossypol derivatives and its analogs implicated by a viral entry blocking mechanism

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.