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Docking-based 3D-QSAR analyses of pyrazole derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors

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Abstract

1,3,4,5-tetrasubstituted-pyrazoles (TPs) have been recently identified as a new class of potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies, followed by docking-based comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), has been used to elucidate the atomic details of the RT/TP interactions and to identify the most important features impacting the TP antiretroviral activity. The final CoMSIA model resulted to be the more predictive, showing r 2ncv  = 0.97, r 2cv  = 0.723, SEE = 0.248, F = 240.291, and r2 pred = 0.77. The results allowed us to obtain useful information for the design of new compounds with improved potency toward WT HIV-1 and also against clinically relevant resistant mutants.

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Acknowledgments

This work was financially supported by the University of Genova.

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Authors and Affiliations

  1. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV n.3, 16132, Genova, Italy

    Elena Cichero & Paola Fossa

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  1. Elena Cichero
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  2. Paola Fossa
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Correspondence to Elena Cichero.

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Cichero, E., Fossa, P. Docking-based 3D-QSAR analyses of pyrazole derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors. J Mol Model 18, 1573–1582 (2012). https://doi.org/10.1007/s00894-011-1190-5

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  • DOI: https://doi.org/10.1007/s00894-011-1190-5

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