1.Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as inhibitors of HIV-1 transcription.
Yan-Boi TANG ; Chuan-Ming ZHANG ; Cheng FANG ; Chun HU ; Li HUANG ; Chin-Ho CHEN ; Zhi-Yan XIAO
Acta Pharmaceutica Sinica 2011;46(6):688-694
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).
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