Base-functionalized carbocyclic nucleosides: design, synthesis, and mechanism of antiviral activity.
New carbocyclic ribonucleosides with unsaturated groups at the C-2 position of the nucleobase were designed as potential RNA antiviral compounds. The design was based on the expectation that the monophosphates of these compounds would be inhibitors of the enzyme, IMPDH. Appropriate methodologies were developed to achieve the target molecules. Results from the initial in vitro antiviral studies are mentioned. The IMPDH-associated mechanism of the antiviral activity of the most active compound is supported by enzyme inhibition studies.
Nair
Vasu
V
Department of Pharmaceutical and Biomedical Sciences and the Center for Drug Discovery, University of Georgia, Athens, Georgia, USA. vnair@rx.uga.edu
Zhang
Fan
F
Ma
Xiaohui
X
Bonsu
Eric
E
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D012327:RNA Virus Infections / Q000188:drug therapy; D012328:RNA Viruses / Q000187:drug effects*; D012263:Ribonucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000998:Antiviral Agents; D012263:Ribonucleosides; D007168:IMP Dehydrogenase