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

页码：5117 / 5122

页数：6

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