Inhibition of HIV-1 envelope-mediated fusion by synthetic batzelladine analogues

Journal of Natural Products
Carole A BewleyLarry E Overman

Abstract

Marine natural products that feature polycyclic guanidine motifs, such as crambescidins and batzelladines, are known to have antiviral activities toward some viruses including HSV and HIV. In this study we evaluated a synthetic library containing 28 batzelladine analogues, the structures of which encompass and surpass variations seen in natural batzelladines, for their ability to inhibit HIV-1 envelope-mediated cell-cell fusion. Clear structure-activity relationships were revealed and indicated that the best inhibitors of fusion were most similar in structure to natural batzelladine F, with IC50 values ranging from 0.8 to 3.0 microM. Proceeding from the earlier finding that some batzelladines block gp120-CD4 binding, modeling studies of inhibitors binding to the CD4 binding site on gp120 were carried out. The lowest energy models suggest a preferred orientation for inhibitor binding that is consistent with the observed structure-activity relationships.

References

Sep 25, 2001·Journal of Magnetic Resonance·C D Schwieters, G M Clore
Feb 14, 2002·Organic Letters·Kazuo NagasawaYuichi Hashimoto
Feb 5, 2003·Journal of Magnetic Resonance·Charles D SchwietersG Marius Clore
Jan 1, 1997·Methods in Enzymology·B C Finzel

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Citations

Feb 24, 2006·Journal of the American Chemical Society·Frederick Cohen, Larry E Overman
Jul 28, 2005·Natural Product Reports·Roberto G S Berlinck, Miriam H Kossuga
Feb 3, 2006·Natural Product Reports·Gillian M Nicholas, Andrew J Phillips
Sep 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Allison OlszewskiGregory A Weiss
Nov 23, 2013·Expert Opinion on Drug Discovery·Muhammad Khawar RaufAmin Badshah
Apr 14, 2016·Marine Drugs·Estelle SfecciMohamed Mehiri
Jul 16, 2016·Journal of Natural Products·Amr El-DemerdashAli Al-Mourabit
Apr 14, 2017·Bioorganic & Medicinal Chemistry·Yunlong ShiJoshua G Pierce
Jul 5, 2017·Chemical Society Reviews·Magnus W P Bebbington
Sep 15, 2005·Chemistry : a European Journal·Jun ShimokawaKazuo Nagasawa
Mar 21, 2012·Angewandte Chemie·Nicholas R Babij, John P Wolfe
Apr 30, 2015·Journal of Natural Products·Mario F C SantosRoberto G S Berlinck

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