1. 2-Aminothiazolones as anti-HIV agents that act as gp120-CD4 inhibitors.
- Author
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Tiberi M, Tintori C, Ceresola ER, Fazi R, Zamperini C, Calandro P, Franchi L, Selvaraj M, Botta L, Sampaolo M, Saita D, Ferrarese R, Clementi M, Canducci F, and Botta M
- Subjects
- Anti-HIV Agents chemistry, CD4 Antigens chemistry, CD4 Antigens metabolism, Cell Line, HIV Envelope Protein gp120 metabolism, HIV Fusion Inhibitors chemistry, Humans, Molecular Docking Simulation, Protein Binding, Anti-HIV Agents pharmacology, CD4 Antigens drug effects, HIV Envelope Protein gp120 antagonists & inhibitors, HIV Fusion Inhibitors pharmacology, HIV-1 drug effects
- Abstract
We report here the synthesis of 2-aminothiazolones along with their biological properties as novel anti-HIV agents. Such compounds have proven to act through the inhibition of the gp120-CD4 protein-protein interaction that occurs at the very early stage of the HIV-1 entry process. No cytotoxicity was found for these compounds, and broad antiviral activities against laboratory strains and pseudotyped viruses were documented. Docking simulations have also been applied to predict the mechanism, at the molecular level, by which the inhibitors were able to interact within the Phe43 cavity of HIV-1 gp120. Furthermore, a preliminary absorption, distribution, metabolism, and excretion (ADME) evaluation was performed. Overall, this study led the basis for the development of more potent HIV entry inhibitors., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
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