Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.
J Comput Aided Mol Des
; 19(4): 243-58, 2005 Apr.
Article
em En
| MEDLINE
| ID: mdl-16163451
ABSTRACT
Molecular docking and molecular dynamics simulation were applied to study the binding mode of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs anti-HIV inhibitors with HIV-1 RT. The results suggest that there is a strong hydrogen bond between DCK O16 and NH of Lys101, and that DCK analogues might act similarly as other types of HIV-1 RT inhibitors. The investigation about drug resistance for DCK shows no remarkable influence on the most frequently observed mutation K103N of HIV-1 RT. Based on the proposed mechanism, some new structures were designed and predicted by a SVM model. All compounds exhibited potent inhibitory activities against HIV replication in H9 lymphocytes with EC50 values lower than 1.95 microM. The rationality of the method was validated by experimental results.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Cânfora
/
Inibidores da Transcriptase Reversa
/
Lactonas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article