Vinod Uchil

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.

Biologically-Validated HIV Integrase Inhibitors with Nucleobase Scaffolds: Structure, Synthesis, Chemical Biology, Molecular Modeling, and Antiviral Activity

Integrase, an enzyme of the pol gene of HIV, is a significant viral target for the discovery of anti-HIV agents. In this presentation, we report on the continuation of our work on the discovery of diketo acids, constructed on nucleobase scaffolds, that are inhibitors of HIV integrase. An example of our synthetic approach to inhibitors with purine nucleobase scaffolds is given. Comparison is made between integrase inhibition data arising from compounds with pyrimidine versus purine nucleobase scaffold. Antiviral results are cited.