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Int. J. Mol. Sci. 2016, 17(8), 1371;

Inhibitory Effect of 2,3,5,6-Tetrafluoro-4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide Derivatives on HIV Reverse Transcriptase Associated RNase H Activities

Dipartimento di Chimica e Farmacia, Università di Sassari, Via Vienna 2, I-07100 Sassari, Italy
Dipartimento di Scienze della Vita e dell’Ambiente-Sezione Biomedica, Università di Cagliari, Cittadella Universitaria SS554, I-09042 Monserrato, Italy
Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, I-43124 Parma, Italy
Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), I-09042 Monserrato, Italy
Authors to whom correspondence should be addressed.
Academic Editor: Claudiu T. Supuran
Received: 28 June 2016 / Revised: 12 August 2016 / Accepted: 15 August 2016 / Published: 20 August 2016
(This article belongs to the Special Issue Enzyme-Inhibitor Interaction as Examples of Molecular Recognition)
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The HIV-1 ribonuclease H (RNase H) function of the reverse transcriptase (RT) enzyme catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate, and represents a suitable target for drug development. A particularly attractive approach is constituted by the interference with the RNase H metal-dependent catalytic activity, which resides in the active site located at the C-terminus p66 subunit of RT. Herein, we report results of an in-house screening campaign that allowed us to identify 4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamides, prepared by the “click chemistry” approach, as novel potential HIV-1 RNase H inhibitors. Three compounds (9d, 10c, and 10d) demonstrated a selective inhibitory activity against the HIV-1 RNase H enzyme at micromolar concentrations. Drug-likeness, predicted by the calculation of a panel of physicochemical and ADME properties, putative binding modes for the active compounds, assessed by computational molecular docking, as well as a mechanistic hypothesis for this novel chemotype are reported. View Full-Text
Keywords: HIV-1 RNase H; click-chemistry; 4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamides; docking HIV-1 RNase H; click-chemistry; 4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamides; docking

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Pala, N.; Esposito, F.; Rogolino, D.; Carcelli, M.; Sanna, V.; Palomba, M.; Naesens, L.; Corona, A.; Grandi, N.; Tramontano, E.; Sechi, M. Inhibitory Effect of 2,3,5,6-Tetrafluoro-4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide Derivatives on HIV Reverse Transcriptase Associated RNase H Activities. Int. J. Mol. Sci. 2016, 17, 1371.

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