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