Synthesis and antiviral activities of novel gossypol derivatives

In this study, a series of novel gossypol derivatives were synthesized and screened in vitro for their anti-HIV-1 and anti-H5N1 activities, respectively. Replacing the aldehyde groups of gossypol with some amino acids not only reduced the cytotoxicity but also enhanced the activities against HIV-1 and H5N1. Compounds 13–17 showed more potent activities against HIV-1 and H5N1 than the other gossypol derivatives. Meanwhile, these compounds also exhibited more potent activities against H5N1 than 1-adamantylamine. The absence of the COONa group in gossypol derivatives resulted in a loss of anti-HIV-1 activity, suggesting that this group might play an important role in mediating the antiviral activity. Time-of-addition assays indicated that compounds 13–17 had the similar mechanism of anti-HIV-1 action with T20. Molecular modeling analysis demonstrated that compounds 13–17 could fit inside the gp41 hydrophobic pocket through hydrogen bonding network, hydrophobic contacts and strong electrostatic interactions.

Graphical abstractSome amino acids substituting the aldehyde groups of gossypol not only lowered the cytotoxicity of gossypol, but also enhanced the activities of gossypol against HIV-1 and H5N1, such as l-Tryptophan, l-Alanine, 2-Aminoisobutyric acid, l-Valine and l-Isoleucine.Figure optionsDownload full-size imageDownload as PowerPoint slide