Zemlicka J, Qiu YL, Lin JS, Cheng YC, Ptak RG, Breitenbach JM, Drach JC, Kern ER; International Conference on Antiviral Research.

Antiviral Res. 1998 Mar; 37: A69 (abstract no. 106).

Karmanos Cancer Institute, Detroit, MI.

The title compounds 1a-1c were synthesized and their antiviral activity against HCMV, HSV-1, HSV-2, EBV, VZV, HIV-1 and HBV was investigated. Adenine analogue 1a was more potent against all these viruses than synadenol (2a) but this effect was accompanied by a varying (Figure: see text) degree of cytotoxicity. In HIV-1/CEM-SS assay EC50 of 1a was 0.05 micromolar and CC50 1.1 micromolar. Guanine derivative 1b was less active against HCMV/HFF than synguanol (2b) with EC50 4.2-7.6 micromolar and CC50 greater than 100 micromolar but more potent toward HBV/2.2.15 (EC50 2 micromolar, CC50 greater than 50 micromolar). Most interesting is the 2,6-diaminopurine analogue 1c which was very effective against HCMV/HFF, HIV-1/CEM-SS, HBV/2.2.15, EBV/Daudi, EBV/H-1 and VZV/HFF with EC50 4-11, 0.2, 0.08, 3.8, 5.5 and 1.1 micromolar, respectively. The corresponding CC50's were 211 (HFF), 35 (CEM), 45 (2.2.15) and 26 (Daudi). Parent compound 2c exhibited a significant activity only against EBV. Possible reasons for a high in vitro efficacy and low cytotoxicity of 1c which contains an unnatural nucleic acid base will be presented. Analogue 1c effective against five different types of viruses, HCMV, HIV-1 and HBV, EBV and VZV at non-cytotoxic concentrations, is a subject of further studies.

Publication Types:

• Meeting Abstracts

Keywords:

• Adenine
• Antiviral Agents
• Cyclopropanes
• Cytomegalovirus
• HIV-1
• Herpesvirus 1, Human
• Herpesvirus 2, Human
• Herpesvirus 3, Human
• Herpesvirus 4, Human
• In Vitro
• Nucleosides
• Prodrugs
• Purine Nucleosides
• Viruses
• synadenol

Other ID:

• 98930192

UI: 102236621

From Meeting Abstracts