Novel natural non-nucleoside inhibitors of HIV-1 reverse transcriptase identified by shape- and structure-based virtual screening techniques.
Eur J Med Chem
; 161: 1-10, 2019 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-30342421
ABSTRACT
In this work we report a parallel application of both docking- and shape-based virtual screening (VS) methods, followed by Molecular Dynamics simulations (MDs), for discovering new compounds able to inhibit the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) RNA-dependent DNA polymerase activity. Specifically, we screened more than 143000 natural compounds commercially available in the ZINC database against the best five RT crystallographic models, taking into account the five approved NNRTIs as query compounds. As a result, 20 hit molecules were selected and tested on biochemical assays for the inhibition of the RNA dependent DNA polymerase RT function and, among them, an indoline pyrrolidine (hit1), an indonyl piperazine (hit2) and an indolyl indolinone (hit3) derivatives were identified as novel non-nucleoside RT inhibitors in the low micromolar range.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
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HIV-1
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Inibidores da Transcriptase Reversa
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Transcriptase Reversa do HIV
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália