Lukashov VV, Krayevsky AA, Kornilayeva GV, Makarova TV, Tarussova NB, Kukhanova MK, Karamov EV; International Conference on AIDS.

Int Conf AIDS. 1992 Jul 19-24; 8: 28 (abstract no. PuA 6104).

D.I.Ivanovsky Institute of Virology, Moscow, Russia.

OBJECTIVES: To evaluate in vitro anti-HIV activity and cytotoxicity of 5'-derivatives of modified nucleosides--the analogs of 5'-monophosphates (5'-hydrogenphosphonates of 2',3'-didesoxynucleosides, ddN-HP, N = T,A,G,C) and compounds, which can be hydrolysed in cells to 5'-monophosphates of ddT (5'-imidazolyl-(I), 5'-morpholyl- (II), 5'-azido- (III), 5'-nitrophenylphosphate (IV)). METHODS: The inhibitory effects of compounds on HIV-infection (RF and BRU strains) were evaluated by HIV antigen ELISA, syncytium formation assay, reverse transcriptase assay and cell viability in MT4, H9 and CEM13 cells and compared with the effects of corresponding nucleosides. RESULTS: This study established that all four ddN-HP are potent and selective inhibitors of HIV-1 replication in different cell/virus models. In some cases selectivity index of 5'-phosphonates was 10-100 times higher than for corresponding nucleosides. Derivatives of 5'-monophosphate of ddT were found to have the same activity as compared with ddT. Selectivity index was less than 50, less than 100, greater than 60, 4.4, 67, 16400 for I, II, III, IV, ddT, AZT, respectively. CONCLUSION: Didesoxynucleoside 5'-phosphonates are shown to be potent and selective inhibitors of HIV-1 replication in vitro.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Anti-HIV Agents
• HIV
• HIV Seropositivity
• HIV-1
• In Vitro
• Nucleosides
• Organophosphorus Compounds
• Phosphonic Acids
• RNA-Directed DNA Polymerase
• Zidovudine
• nitrophenylphosphate

Other ID:

• 92404188

UI: 102201902

From Meeting Abstracts