8
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Hologram quantitative structure–activity relationship and comparative molecular field analysis studies within a series of tricyclic phthalimide HIV-1 integrase inhibitors

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Acquired immunodeficiency syndrome is a public health problem worldwide caused by the Human immunodeficiency virus (HIV). Treatment with antiretroviral drugs is the best option for viral suppression, reducing morbidity and mortality. However, viral resistance in HIV-1 therapy has been reported. HIV-1 integrase (IN) is an essential enzyme for effective viral replication and an attractive target for the development of new inhibitors. In the study reported here, two- and three-dimensional quantitative structure–activity relationship (2D/3D-QSAR) studies, applying hologram quantitative structure–activity relationship (HQSAR) and comparative molecular field analysis (CoMFA) methods, respectively, were performed on a series of tricyclic phthalimide HIV-1 IN inhibitors. The best HQSAR model ( q 2 = 0.802, r 2 = 0.972) was obtained using atoms, bonds, and connectivity as the fragment distinction, a fragment size of 2–5 atoms, hologram length of 61 bins, and six components. The best CoMFA model ( q 2 = 0.748, r 2 = 0.974) was obtained with alignment of all atoms of the tricyclic phthalimide moiety (alignment II). The HQSAR contribution map identified that the carbonyl-hydroxy-aromatic nitrogen motif made a positive contribution to the activity of the compounds. Furthermore, CoMFA contour maps suggested that bulky groups in meta and para positions in the phenyl ring would increase the biological activity of this class. The conclusions of this work may lead to a better understanding of HIV-1 IN inhibition and contribute to the design of new and more potent derivatives.

          Related collections

          Most cited references 22

          • Record: found
          • Abstract: not found
          • Article: not found

          Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Integrase inhibitors to treat HIV/AIDS.

            HIV integrase is a rational target for treating HIV infection and preventing AIDS. It took approximately 12 years to develop clinically usable inhibitors of integrase, and Phase I clinical trials of integrase inhibitors have just begun. This review focuses on the molecular basis and rationale for developing integrase inhibitors. The main classes of lead compounds are also described, as well as the concept of interfacial inhibitors of protein-nucleic-acid interactions that might apply to the clinically used strand-transfer inhibitors.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              2012 FDA drug approvals.

               Asher Mullard (2013)
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2013
                05 September 2013
                : 7
                : 953-961
                Affiliations
                [1 ]Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farmácia, Laboratório de Modelagem Molecular and QSAR (ModMolQSAR), Rio de Janeiro, RJ, Brazil
                [2 ]Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Química, Laboratório de Modelagem Molecular (LabMMol), Rio de Janeiro, RJ, Brazil
                [3 ]Universidade Federal Fluminense (UFF), Faculdade de Farmácia, Laboratório de Química Medicinal Computacional (LabQMC), Niterói, RJ, Brazil
                [4 ]Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Farmácia, Laboratório de Tecnologia Farmacêutica Industrial (LabTIF), Rio de Janeiro, RJ, Brazil
                Author notes
                Correspondence: Carlos Rangel, Rodrigues, Laboratory of Molecular Modeling and QSAR, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, 21949-900, RJ, Brazil, Tel +55 21 2260 9192, Email rangelfarmacia@ 123456gmail.com
                Article
                dddt-7-953
                10.2147/DDDT.S47057
                3771852
                24039405
                © 2013 Magalhães et al. This work is published by Dove Medical Press Ltd, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Ltd, provided the work is properly attributed.

                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                3d-qsar, aids, comfa, hqsar, 2d/3d-qsar

                Comments

                Comment on this article