Design of inhibitors of ODCase.
ODCase is a highly proficient enzyme responsible for the decarboxylation of orotidine monophosphate to generate uridine monophosphate. ODCase has attracted early attention due to its interesting mechanism of catalysis. In order to exploit therapeutic advantages due to the inhibition of ODCase, one must have selective inhibitors of this enzyme from the pathogen, or a dysregulated molecular mechanism involving ODCase. ODCase inhibitors have potential applications as anticancer agents, antiviral agents, antimalarial agents and potentially act against other parasitic diseases. A variety of C6-substituted uridine monophosphate derivatives have shown excellent inhibition of ODCase. 6-iodouridine is a potent inhibitor of the malaria parasite, and its monophosphate form covalently inhibits ODCase. A variety of inhibitors of ODCase with potential applications as therapeutic agents are discussed in this review.
Center for Molecular Design & Preformulations, & Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 1L7, Canada.
Sourabh
S
Mundra
Lakshmi P
LP
Kotra
D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects; D014780:Viruses / Q000187:drug effects
D000962:Antimalarials; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009964:Orotidine-5'-Phosphate Decarboxylase