Design, synthesis, and biological evaluation of novel trifluoromethyl indoles as potent HIV-1 NNRTIs with an improved drug resistance profile.
Org Biomol Chem
; 12(21): 3446-58, 2014 Jun 07.
Article
en En
| MEDLINE
| ID: mdl-24752610
ABSTRACT
A novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. Preliminary SAR and docking studies of detailed binding mode provided some insights for discovery of more potent NNRTIs.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
VIH-1
/
Inhibidores de la Transcriptasa Inversa
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Farmacorresistencia Viral
/
Indoles
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article