Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and d-glucosamine

A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV-1 activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and d-glucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, d-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1IIIB into target cell, which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and d-glucosamine were important moities to prepare gossypol derivatives as HIV-1 entry inhibitors besides certain amino acids.

Graphical abstractCertain oligopeptides and d-glucosamine are important moities to prepare gossypol derivatives as HIV-1 entry inhibitors besides certain amino acids.Figure optionsDownload full-size imageDownload as PowerPoint slide