Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as inhibitors of HIV-1 transcription.
- Author:
Yan-Boi TANG
1
;
Chuan-Ming ZHANG
;
Cheng FANG
;
Chun HU
;
Li HUANG
;
Chin-Ho CHEN
;
Zhi-Yan XIAO
Author Information
1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Benzodiazepinones;
chemical synthesis;
chemistry;
pharmacology;
Cell Line, Tumor;
HIV Long Terminal Repeat;
genetics;
HIV-1;
genetics;
Humans;
Transcription, Genetic;
drug effects;
tat Gene Products, Human Immunodeficiency Virus;
antagonists & inhibitors
- From:
Acta Pharmaceutica Sinica
2011;46(6):688-694
- CountryChina
- Language:Chinese
-
Abstract:
HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1 transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of novel benzodiazepine analogs were designed as beta-turn mimetics and prepared from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through different synthetic routes. Preliminary biological evaluation indicated that compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM-BI cells under the concentration of 100 micromol x L(-1).
