Antimicrobial Agents and Chemotherapy 2014-06-01

2-Aminothiazolones as anti-HIV agents that act as gp120-CD4 inhibitors.

Marika Tiberi, Cristina Tintori, Elisa Rita Ceresola, Roberta Fazi, Claudio Zamperini, Pierpaolo Calandro, Luigi Franchi, Manikandan Selvaraj, Lorenzo Botta, Michela Sampaolo, Diego Saita, Roberto Ferrarese, Massimo Clementi, Filippo Canducci, Maurizio Botta

Index: Antimicrob. Agents Chemother. 58(6) , 3043-52, (2014)

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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.