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

• Published in: Chinese chemical letters Vol. 25; no. 7; pp. 1052 - 1056
• Main Authors: Yang, Jian, Li, Ju-Rong, Yang, Jing-Xiang, Li, Long-Long, Ouyang, Wen-Jie, Wu, Shu-Wen, Zhang, Fang
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.07.2014
• Subjects: Anti-HIV-1; d-Glucosamine derivative; D-氨基葡萄糖; Gossypol; Oligopeptide derivative; 偶联物; 合成; 寡肽; 抗HIV-1活性; 棉酚; 胺衍生物; 葡萄糖胺; Anti-HIV-1; Oligopeptide derivative; Gossypol; d-Glucosamine derivative
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2014.05.030

A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine 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.