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
Y1 - 2007
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.
KW - Benzoylbenzimidazole derivatives
KW - HIV-1 RT
KW - Molecular modeling
KW - NNRTIs
UR - http://www.scopus.com/inward/record.url?scp=41549136583&partnerID=8YFLogxK
U2 - 10.4067/S0717-97072007000400002
DO - 10.4067/S0717-97072007000400002
M3 - Article
AN - SCOPUS:41549136583
SN - 0717-9324
VL - 52
SP - 1281
EP - 1287
JO - Journal of the Chilean Chemical Society
JF - Journal of the Chilean Chemical Society
IS - 4
ER -