Open AccessBI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine
Author(s) -
Richman Dd,
Alan S. Rosenthal,
Mark T. Skoog,
Robert J. Eckner,
TingChao Chou,
John P. Sabo,
Vincent J. Merluzzi
Publication year - 1991
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.35.2.305
Subject(s) - zidovudine , virology , reverse transcriptase , hela , lymphoblast , virus , biology , human immunodeficiency virus (hiv) , cell culture , viral disease , rna , biochemistry , gene , genetics
A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. The lead compound, BI-RG-587, had a 50% inhibitory concentration of 84 nM against HIV-1 reverse transcriptase activity. This compound reduced plaque formation of HIV-1 in HeLa cells expressing the CD4 receptor by 50% at 15 nM. BI-RG-587 at comparable concentrations inhibited the production of p24 antigen following the acute infection of CEM T-lymphoblastoid cells or primary human monocyte-derived macrophages with HIV-1. No inhibitory effects against HIV-2 or against three picornaviruses were detected. Zidovudine (3'-azido-3'-deoxythymidine [AZT])-susceptible and AZT-resistant isolates of HIV-1 were equally susceptible to BI-RG-587. AZT and BI-RG-587 exhibited synergistic inhibition of HIV-1BRU at all concentrations examined.