Computer-assisted design of dual-target anti-HIV-1 compounds

Guimarães, Maria Carolina; Silva, Daniel G.; Mota, Estella G. da; Cunha, Elaine F. F. da; Freitas, Matheus P.

doi:10.1007/s00044-013-0765-3

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…Computational QSAR studies are often used to filter virtually large compounds libraries, to eliminate the molecules with predicted toxic or poor pharmacokinetic properties early on and to narrow the libraries to drug-like or lead-like compounds ( Dudek et al 2006) . Some QSAR studies applied to RT have been reported ( Gaudio & Montanari 2002 , Gayen et al 2004 , Guimarães et al 2014 , Dong & Ren 2015 , Nazar et al 2015) .…”

Section: Qsar and Pharmacophore Studiesmentioning

confidence: 99%

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Santos

Ferreira

Caffarena

2015

Mem. Inst. Oswaldo Cruz

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Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

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Section: Qsar and Pharmacophore Studiesmentioning

confidence: 99%

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Santos

Ferreira

Caffarena

2015

Mem. Inst. Oswaldo Cruz

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“…The three-dimensional structure of each inhibitor was built using the program PC Spartan Pro [20] and its partial charges were calculated by the semiempirical PM3 method. The compounds were docked into the protein LdTUB using Molegro Virtual Docker (MVD) software [21,22]. The binding site was limited to a sphere with a 9Å radius.…”

Section: Molecular Dockingmentioning

confidence: 99%

In SilicoStudy ofLeishmania donovaniα-βTubulin and Inhibitors

Assis¹,

Mancini²,

Ramalho

et al. 2014

Journal of Chemistry

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Leishmania donovani is a parasite that causes visceral leishmaniasis, a severe form of leishmaniasis that affects vital organs. An important target for the treatment of this disease is the protein -tubulin, which was modeled in this paper and proposed as a target for the treatment of visceral leishmaniasis. Two classes of compounds were studied, dinitroanilines and oxadiazoles. According to the docking results, dinitroanilines interact better with the L loop domain and oxadiazoles interact better with the colchicine domain. Experimental2.1. Homology Modeling. The modeling began with the systematic search in the database Expasy [11] for primary structures of the protein -tubulin in LdTUB using the server Protein Knowledgebase (UniProtKB) [12] as a search tool. Thus, we obtained the primary alpha (Q25262 LEIDO, 451 amino acids) and beta (I3W8N7 LEIDO, 442 amino acids) sequences. The crystal structure of pig tubulin heterodimer (protein data bank code: 1TUB) was chosen as the template for the construction of the three-dimensional LdTUB model, as it showed the highest sequence identity therewith [13].

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“…Organosulfones are recognized as privileged functional groups having an immense application in agrochemicals, pharmaceuticals, and material chemistry . Among them, aryl sulfones are known to be antifungal, antibacterial, and antitumoral agents as well as the inhibitors of HIV-1 reverse transcriptase Figure shows selected biologically active molecules featuring an aryl sulfone pharmacophore. ,, In addition to their medicinal importance, aryl sulfones are also versatile reactive intermediates in organic synthesis and used in well-known organic transformations such as the Ramberg–Backlund reaction and the Julia olefination .…”

Section: Introductionmentioning

confidence: 99%

“…Among them, aryl sulfones are known to be antifungal, antibacterial, and antitumoral agents as well as the inhibitors of HIV-1 reverse transcriptase Figure shows selected biologically active molecules featuring an aryl sulfone pharmacophore. ,, In addition to their medicinal importance, aryl sulfones are also versatile reactive intermediates in organic synthesis and used in well-known organic transformations such as the Ramberg–Backlund reaction and the Julia olefination . In the past decades, tremendous efforts have been devoted to the development of novel methodologies for the incorporation of sulfone-containing substituents into organic frameworks .…”

Section: Introductionmentioning

confidence: 99%

“…In the past decades, tremendous efforts have been devoted to the development of novel methodologies for the incorporation of sulfone-containing substituents into organic frameworks . Due to their compelling synthetic utility and substantial biological ,,− as well as material applications, the development of facile methods for aryl sulfones has stimulated considerable interest.…”

Section: Introductionmentioning

confidence: 99%

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Transition-Metal-Free Regioselective One-Pot Synthesis of Aryl Sulfones from Sodium Sulfinates via Quinone Imine Ketal

2019

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A novel, efficient, and regioselective transition-metal-free one-pot synthesis of aryl sulfones via the reactive quinone imine ketal intermediate is demonstrated using easily accessible bench-stable sulfinate salts. A broad range of functionality on p-anisidine substrates as well as sulfinate salts was tolerated under mild reaction conditions to provide the corresponding aryl sulfones in good to excellent yields.

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Computer-assisted design of dual-target anti-HIV-1 compounds

Cited by 8 publications

References 17 publications

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

In SilicoStudy ofLeishmania donovaniα-βTubulin and Inhibitors

Transition-Metal-Free Regioselective One-Pot Synthesis of Aryl Sulfones from Sodium Sulfinates via Quinone Imine Ketal

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