Comparative effects of two acycleonucleoside derivatives on ultrastructure and replication of guinea pig cytomegalovirus in cultured cells.
Two antiviral agents, compound 164, also known as 2'-nor-cGMP, 9-[(2-hydroxy-1-3-2-dioxophosphorinan-5-yl)-oxymethyl]-guani ne P-oxide, and compound 102, 4-amino-5-bromo-7-(2-hydroxyethoxymethyl)-pyrrolo-(2-3-d)-pyrimidine, together with their parental drugs, 2-deoxyguanosine (DHPG) and acyclovir (ACV), were evaluated for their antiviral activities against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo (GPE) cells. The two compounds were demonstrated to be more potent against GPCMV replication when compared to their parental drugs DHPG and ACV. Compound 164 was the most potent of the four compounds tested, with ED50 values being approximately 20-, 80-, and 180-fold more potent than those of DHPG, compound 102, and ACV, respectively. Compounds 164 and 102 were slightly more cytotoxic to uninfected GPE cells, but their selectivity (therapeutic) indexes were higher than those of their parental drugs. Of the four antiviral agents tested, compound 164 had the highest selectivity index which was 8-, 30-, and 50-fold higher than that of DHPG, compound 102, and ACV, respectively. Ultrastructural studies suggest that compounds 164 and 102 have different mechanisms of inhibiting GPCMV replication in cultured GPE cells.
Yang
Z H
ZH
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Conn.
Klein
S
S
Hsiung
G D
GD
D000212:Acyclovir / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D009024:Morphogenesis / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011247:Pregnancy; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D011743:Pyrimidines; D011758:Pyrroles; C061594:4-amino-5-bromo-7-(2-hydroxyethoxymethyl)pyrrolo(2,3-d)pyrimidine; D006147:Guanine; C045511:9-((2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl)guanine P-oxide; D003849:Deoxyguanosine; D000212:Acyclovir