1-Benzoyl-2-(2-nitrophenyl)-1H-benzimidazole derivatives: A novel approach to the development of new HIV-1 reverse transcriptase inhibitors

David Vásquez, Carlos F. Lagos, Jaime Mella-Raipán, Luis González, Roberto Ebensperger, M. Javiera Alvarez-Figueroa, Edmundo Sáez, Hernán Pessoa-Mahana, Raúl Araya-Secchp, Angel González-Wong, Tomás Pérez-Acle, C. David Pessoa-Mahana

Resultado de la investigación: Article

6 Citas (Scopus)

Resumen

A novel approach to the development of a new class of HIV-1 RT inhibitors is reported. The 1-benzoyl-2-aryl-1H-benzimidazole series was designed as a combination of two previously reported active scaffolds, the benzimidazole and benzoyl moieties. The active compounds of the series effectively blocked the reverse transcription in the micromolar range in an in vitro assay containing the wild-type enzyme. We have demonstrated that the 2-nitrophenyl C-2 substituent is an important structural feature for the desired biological activity in this series. Molecular docking experiments suggest that the active compounds adopt a butterflylike conformation within the binding pocket of the enzyme, with the benzoyl moiety located in an extended hydrophobic region defined mainly by Tyrl 81, Tyrl 88, and Trp229.

Idioma originalEnglish
Páginas (desde-hasta)1281-1287
Número de páginas7
PublicaciónJournal of the Chilean Chemical Society
Volumen52
N.º4
DOI
EstadoPublished - 1 ene 2007

Huella dactilar

Reverse Transcriptase Inhibitors
Derivatives
Enzymes
Transcription
Bioactivity
Scaffolds
Conformations
Assays
Experiments
Human immunodeficiency virus 1 reverse transcriptase
benzimidazole

ASJC Scopus subject areas

  • Chemistry(all)

Citar esto

Vásquez, D., Lagos, C. F., Mella-Raipán, J., González, L., Ebensperger, R., Alvarez-Figueroa, M. J., ... Pessoa-Mahana, C. D. (2007). 1-Benzoyl-2-(2-nitrophenyl)-1H-benzimidazole derivatives: A novel approach to the development of new HIV-1 reverse transcriptase inhibitors. Journal of the Chilean Chemical Society, 52(4), 1281-1287. https://doi.org/10.4067/S0717-97072007000400002
Vásquez, David ; Lagos, Carlos F. ; Mella-Raipán, Jaime ; González, Luis ; Ebensperger, Roberto ; Alvarez-Figueroa, M. Javiera ; Sáez, Edmundo ; Pessoa-Mahana, Hernán ; Araya-Secchp, Raúl ; González-Wong, Angel ; Pérez-Acle, Tomás ; Pessoa-Mahana, C. David. / 1-Benzoyl-2-(2-nitrophenyl)-1H-benzimidazole derivatives : A novel approach to the development of new HIV-1 reverse transcriptase inhibitors. En: Journal of the Chilean Chemical Society. 2007 ; Vol. 52, N.º 4. pp. 1281-1287.
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abstract = "A novel approach to the development of a new class of HIV-1 RT inhibitors is reported. The 1-benzoyl-2-aryl-1H-benzimidazole series was designed as a combination of two previously reported active scaffolds, the benzimidazole and benzoyl moieties. The active compounds of the series effectively blocked the reverse transcription in the micromolar range in an in vitro assay containing the wild-type enzyme. We have demonstrated that the 2-nitrophenyl C-2 substituent is an important structural feature for the desired biological activity in this series. Molecular docking experiments suggest that the active compounds adopt a butterflylike conformation within the binding pocket of the enzyme, with the benzoyl moiety located in an extended hydrophobic region defined mainly by Tyrl 81, Tyrl 88, and Trp229.",
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Vásquez, D, Lagos, CF, Mella-Raipán, J, González, L, Ebensperger, R, Alvarez-Figueroa, MJ, Sáez, E, Pessoa-Mahana, H, Araya-Secchp, R, González-Wong, A, Pérez-Acle, T & Pessoa-Mahana, CD 2007, '1-Benzoyl-2-(2-nitrophenyl)-1H-benzimidazole derivatives: A novel approach to the development of new HIV-1 reverse transcriptase inhibitors', Journal of the Chilean Chemical Society, vol. 52, n.º 4, pp. 1281-1287. https://doi.org/10.4067/S0717-97072007000400002

1-Benzoyl-2-(2-nitrophenyl)-1H-benzimidazole derivatives : A novel approach to the development of new HIV-1 reverse transcriptase inhibitors. / Vásquez, David; Lagos, Carlos F.; Mella-Raipán, Jaime; González, Luis; Ebensperger, Roberto; Alvarez-Figueroa, M. Javiera; Sáez, Edmundo; Pessoa-Mahana, Hernán; Araya-Secchp, Raúl; González-Wong, Angel; Pérez-Acle, Tomás; Pessoa-Mahana, C. David.

En: Journal of the Chilean Chemical Society, Vol. 52, N.º 4, 01.01.2007, p. 1281-1287.

Resultado de la investigación: Article

TY - JOUR

T1 - 1-Benzoyl-2-(2-nitrophenyl)-1H-benzimidazole derivatives

T2 - A novel approach to the development of new HIV-1 reverse transcriptase inhibitors

AU - Vásquez, David

AU - Lagos, Carlos F.

AU - Mella-Raipán, Jaime

AU - González, Luis

AU - Ebensperger, Roberto

AU - Alvarez-Figueroa, M. Javiera

AU - Sáez, Edmundo

AU - Pessoa-Mahana, Hernán

AU - Araya-Secchp, Raúl

AU - González-Wong, Angel

AU - Pérez-Acle, Tomás

AU - Pessoa-Mahana, C. David

PY - 2007/1/1

Y1 - 2007/1/1

N2 - A novel approach to the development of a new class of HIV-1 RT inhibitors is reported. The 1-benzoyl-2-aryl-1H-benzimidazole series was designed as a combination of two previously reported active scaffolds, the benzimidazole and benzoyl moieties. The active compounds of the series effectively blocked the reverse transcription in the micromolar range in an in vitro assay containing the wild-type enzyme. We have demonstrated that the 2-nitrophenyl C-2 substituent is an important structural feature for the desired biological activity in this series. Molecular docking experiments suggest that the active compounds adopt a butterflylike conformation within the binding pocket of the enzyme, with the benzoyl moiety located in an extended hydrophobic region defined mainly by Tyrl 81, Tyrl 88, and Trp229.

AB - A novel approach to the development of a new class of HIV-1 RT inhibitors is reported. The 1-benzoyl-2-aryl-1H-benzimidazole series was designed as a combination of two previously reported active scaffolds, the benzimidazole and benzoyl moieties. The active compounds of the series effectively blocked the reverse transcription in the micromolar range in an in vitro assay containing the wild-type enzyme. We have demonstrated that the 2-nitrophenyl C-2 substituent is an important structural feature for the desired biological activity in this series. Molecular docking experiments suggest that the active compounds adopt a butterflylike conformation within the binding pocket of the enzyme, with the benzoyl moiety located in an extended hydrophobic region defined mainly by Tyrl 81, Tyrl 88, and Trp229.

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KW - Molecular modeling

KW - NNRTIs

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