Activity and molecular modeling of a new small molecule active against NNRTI-resistant HIV-1 mutants

被引：13
|
作者：
Carta, Antonio [1 ]
Pricl, Sabrina [2 ]
Piras, Sandra [1 ]
Fermeglia, Maurizio [2 ]
La Colla, Paolo [3 ]
Loddo, Roberta [3 ]
机构：
[1] Univ Sassari, Dipartimento Farmaco Chim Tossicol, I-07100 Sassari, Italy
[2] Dipartimento Ingn Chim, Laboratorio MOSE, I-34127 Trieste, Italy
[3] Univ Cagliari, Dipartimento Sci & Tecnol Biomed, Sez Microbiol & Virol Gen & Biotecnol Microb, I-09042 Cagliari, Italy
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 12期
关键词：
HIV; NNRTI resistant mutants; HIV-1wt RT assay; Molecular modeling; REVERSE-TRANSCRIPTASE; IN-VITRO; FREE-ENERGIES; REPLICATION; DERIVATIVES; INHIBITION; EFAVIRENZ; DYNAMICS; DMP-266; BINDING;
D O I：
10.1016/j.ejmech.2009.08.012
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
In this preliminary study we report the antiviral screening of triazolo[4,5-g]quinoline derivatives (compounds 1-6). 4,9-Dihydrotriazolo[4,5-g]quinoline-1-oxide (1) stood out as a new, small molecule endowed with a selective, promising activity in cell-based assays against HIV-1wt and clinically relevant NNRTI resistant mutants. In order to identify the molecular target, compound 1 was assayed in enzyme assay against the HIV-1wt RT. The molecular modeling strategy adopted yielded a rationale, in terms of molecular interactions and free energy of binding, for the possible reasons of the activity of this compound against NNRTI-resistant HIV-1 mutants with the RT isoforms K103N and Y181C. (C) 2009 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：5117 / 5122
页数：6
相关论文
共 50 条
  • [1] Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants
    Smith, Steven J.
    Pauly, Gary T.
    Akram, Aamir
    Melody, Kevin
    Ambrose, Zandrea
    Schneider, Joel P.
    Hughes, Stephen H.
    [J]. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2016, 72 (05) : 485 - 491
  • [2] α-substituted acetanilides:: HIV-1 NNRTIs with improved activity against NNRTI-resistant viruses
    Miller, M. D.
    [J]. ANTIVIRAL THERAPY, 2007, 12 (05) : S31 - S31
  • [3] In vitro microbicide activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 against NNRTI-resistant HIV-1
    Hossain, MM
    Parniak, MA
    [J]. ANTIVIRAL THERAPY, 2005, 10 : S170 - S170
  • [4] In vitro microbicide activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 against NNRTI-resistant HIV-1
    Hossain, MM
    Parniak, MA
    [J]. ANTIVIRAL THERAPY, 2005, 10 (04) : S170 - S170
  • [5] A novel NNRTI class with potent anti-HIV activity against NNRTI-resistant viruses
    Raney, Anneke
    Hamatake, Robert
    Xu, Wen
    Girardet, Jean-Luc
    Vernier, Jean-Michel
    Yeh, Li-Tain
    Quart, Barry
    [J]. ANTIVIRAL RESEARCH, 2008, 78 (02) : A47 - A47
  • [6] α-Substituted acetanilides:: HIV-1NNRTIs with improved activity against NNRTI-resistant viruses
    Miller, M. D.
    [J]. ANTIVIRAL THERAPY, 2007, 12 : S31 - S31
  • [7] Novel 8-substituted dipyridodiazepinone inhibitors with broad-spectrum activity against NNRTI-resistant HIV-1
    Yoakim, C
    Bonneau, PR
    Deziel, R
    Doyon, L
    Duan, J
    Guse, I
    Haché, B
    Landry, S
    Malenfant, E
    Naud, J
    Ogilvie, WW
    O'Meara, JA
    Plante, R
    Simoneau, B
    Thavonekham, B
    Bös, M
    Cordingley, MG
    [J]. ANTIVIRAL RESEARCH, 2004, 62 (02) : A31 - A31
  • [8] TMC278, a Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI), Active against Wild-Type and NNRTI-Resistant HIV-1
    Azijn, Hilde
    Tirry, Ilse
    Vingerhoets, Johan
    de Bethune, Marie-Pierre
    Kraus, Guenter
    Boven, Katia
    Jochmans, Dirk
    Van Craenenbroeck, Elke
    Picchio, Gaston
    Rimsky, Laurence T.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2010, 54 (02) : 718 - 727
  • [9] Etravirine: A Second-Generation Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) Active Against NNRTI-Resistant Strains of HIV
    Schiller, Daryl S.
    Youssef-Bessler, Manal
    [J]. CLINICAL THERAPEUTICS, 2009, 31 (04) : 692 - 704
  • [10] Novel 8-substituted dipyridodiazepinone inhibitors with broad-spectrum of activity against NNRTI-resistant HIV-1.
    Yoakim, C
    Bonneau, PR
    Déziel, R
    Doyon, L
    Duan, JM
    Guse, I
    Haché, B
    Landry, S
    Malenfant, E
    Naud, J
    Ogilvie, WW
    O'Meara, JA
    Plante, R
    Thavonekham, B
    Simoneau, B
    Boes, M
    Cordingley, MG
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2004, 228 : U931 - U931
12345