Carbocyclic analogue of 3-deazaadenosine: a novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target.
The carbocyclic analogue of 3-deazaadenosine (3-deaza-C-Ado) has been synthesized and found to have antiviral activity in cell culture against herpes simplex virus type 1, vaccinia virus, and HL-23 C-type virus. It is relatively noncytotoxic at effective antiviral concentrations and is not subject to deamination or phosphorylation. It acts as a competitive inhibitor of S-adenosyl-L-homocysteine hydrolase, is at best a poor substrate, and does not inactivate the enzyme significantly. 3-Deaza-C-Ado may cause a selective inhibition of the methylation of the polynucleotide 5' cap of viral mRNA via higher cellular concentrations of S-adenosyl-L-homocysteine, resulting from the inhibition of S-adenosylhomocysteine hydrolase in infected cells, since increases in the intracellular level of S-adenosylhomocysteine, but no effects on DNA or RNA synthesis, were observed after incubation of these cells with it.
D043383:Adenosylhomocysteinase; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006224:Cricetinae; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D051381:Rats; D012263:Ribonucleosides / Q000138:chemical synthesis*; D014372:Tubercidin / Q000138:chemical synthesis* / Q000494:pharmacology / Q000031:analogs & derivatives
D000998:Antiviral Agents; D012263:Ribonucleosides; C034072:carbocyclic 3-deazaadenosine; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D014372:Tubercidin