Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions
Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and...
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doaj-1ad3314eb0a74fe68b34c1c275aa5a3f2021-07-15T15:42:04ZengMDPI AGMolecules1420-30492021-06-01263821382110.3390/molecules26133821Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated FunctionsRita Meleddu0Angela Corona1Simona Distinto2Filippo Cottiglia3Serenella Deplano4Lisa Sequeira5Daniela Secci6Alessia Onali7Erica Sanna8Francesca Esposito9Italo Cirone10Francesco Ortuso11Stefano Alcaro12Enzo Tramontano13Péter Mátyus14Elias Maccioni15Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyDipartimento di Scienze della Salute, Università Magna Graecia di Catanzaro, Campus ‘S. Venuta’, Viale Europa, 88100 Catanzaro, ItalyDipartimento di Scienze della Salute, Università Magna Graecia di Catanzaro, Campus ‘S. Venuta’, Viale Europa, 88100 Catanzaro, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyInstitute of Digital Health Sciences, Faculty of Health and Public Services, Semmelweis University, Ferenc tér 15, 1094 Budapest, HungaryDepartment of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Monserrato, 09042 Cagliari, ItalyCurrent therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide (<b>EMAC2063</b>) was the most potent towards RNaseH (IC<sub>50</sub> = 4.5 mM)- and RDDP (IC<sub>50</sub> = 8.0 mM) HIV RT-associated functions.https://www.mdpi.com/1420-3049/26/13/3821HIV-RTribonuclease Hdual inhibitorsdockingputative binding |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rita Meleddu Angela Corona Simona Distinto Filippo Cottiglia Serenella Deplano Lisa Sequeira Daniela Secci Alessia Onali Erica Sanna Francesca Esposito Italo Cirone Francesco Ortuso Stefano Alcaro Enzo Tramontano Péter Mátyus Elias Maccioni |
spellingShingle |
Rita Meleddu Angela Corona Simona Distinto Filippo Cottiglia Serenella Deplano Lisa Sequeira Daniela Secci Alessia Onali Erica Sanna Francesca Esposito Italo Cirone Francesco Ortuso Stefano Alcaro Enzo Tramontano Péter Mátyus Elias Maccioni Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions Molecules HIV-RT ribonuclease H dual inhibitors docking putative binding |
author_facet |
Rita Meleddu Angela Corona Simona Distinto Filippo Cottiglia Serenella Deplano Lisa Sequeira Daniela Secci Alessia Onali Erica Sanna Francesca Esposito Italo Cirone Francesco Ortuso Stefano Alcaro Enzo Tramontano Péter Mátyus Elias Maccioni |
author_sort |
Rita Meleddu |
title |
Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions |
title_short |
Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions |
title_full |
Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions |
title_fullStr |
Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions |
title_full_unstemmed |
Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions |
title_sort |
exploring new scaffolds for the dual inhibition of hiv-1 rt polymerase and ribonuclease associated functions |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-06-01 |
description |
Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide (<b>EMAC2063</b>) was the most potent towards RNaseH (IC<sub>50</sub> = 4.5 mM)- and RDDP (IC<sub>50</sub> = 8.0 mM) HIV RT-associated functions. |
topic |
HIV-RT ribonuclease H dual inhibitors docking putative binding |
url |
https://www.mdpi.com/1420-3049/26/13/3821 |
work_keys_str_mv |
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