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-H(5)N(1) 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 H(5)N(1). Compounds 13-17 showed more potent activities against HIV-1 and H(5)N(1) than the other gossypol derivatives. Meanwhile, these compounds also exhibited more potent activities against H(5)N(1) 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.
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, China. Yanj502@yahoo.com.cn
Jian
J
Yang
Fang
F
Zhang
Jurong
J
Li
Gang
G
Chen
Shuwen
S
Wu
Wenjie
W
Ouyang
Wei
W
Pan
Rui
R
Yu
Jingxiang
J
Yang
Po
P
Tien
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006072:Gossypol / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D006072:Gossypol