Enantioselective inhibition of reverse transcriptase (RT) of HIV-1 by non-racemic indole-based trifluoropropanoates developed by asymmetric catalysis using recyclable organocatalysts.
Org Biomol Chem
; 11(48): 8463-75, 2013 Dec 28.
Article
en En
| MEDLINE
| ID: mdl-24202207
ABSTRACT
Herein, we report the development of efficient inhibitors of reverse transcriptase (RT) of HIV-1 based on indole-alkyl trifluoropyruvate derivatives by a TZM-bl cell assay. The inhibitory activities of the two enantiomers and the corresponding racemic mixture have been compared. TZM-bl cells exhibited strong enantioselective discrimination for the (R)-configuration, among these indole derivatives, the most active compound R-12, with a 5-NO2 substituent, gave the best result when tested in the TZM-bl cells on HIV virus type HIV-1IIIB, with an EC50 value of 0.019 µM, CC50 value of 210.697 µM and SI (selectivity index, CC50/EC50) value of 11,089, respectively. The cell test showed that, in most cases, the R-enantiomer was superior to the Rac-mixture, which was better than the corresponding S-enantiomer. The results indicated that the R-enantiomer is the most favorable configuration as an efficient HIV-1 inhibitor. Molecular modeling studies suggested a structural basis for the enantioselectivity of RT towards this class of molecules.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
VIH-1
/
Inhibidores de la Transcriptasa Inversa
/
Transcriptasa Inversa del VIH
/
Indoles
Límite:
Humans
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
China