Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 22, Issue 3, Pages 1415-1420Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.12.076
Keywords
Gossypol; Amino acid derivative; Aminoalkanoic acid derivative; HIV-1; Avian influenza virus
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Funding
- National Natural Science Foundation of China [30770228]
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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. (C) 2011 Elsevier Ltd. All rights reserved.
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