IMPDH as a biological probe for RNA antiviral drug discovery: synthesis, enzymology, molecular docking, and antiviral activity of new ribonucleosides with surrogate bases.
Our interest in the discovery of molecules with antiviral activity against RNA viruses led us to the design of ribonucleosides with surrogate bases with the intent of using inhibition of inosine monophosphate dehydrogenase (IMPDH) as a probe for antiviral drug discovery. A general methodology for the preparation of these compounds is discussed. Kinetic parameters of the inhibition studies with IMPDH, which were carried out spectrophotometrically by monitoring the formation of NADH, are given. Antiviral information and correlation of activity with IMPDH inhibition are discussed.
Nair
Vasu
V
Center for Drug Discovery and the Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602-2352, USA. vnair@rx.uga.edu
Ma
Xiaohui
X
Shu
Qingning
Q
Zhang
Fan
F
Uchil
Vinod
V
Cherukupalli
Govardhan R
GR
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012328:RNA Viruses / Q000187:drug effects*; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D012263:Ribonucleosides; D007168:IMP Dehydrogenase