title: Inosine 5'-Monophosphate Dehydrogenase (IMPDH) as a Potential Target for the Development of a New Generation of Antiprotozoan Agents.
abstract: Inosine-5'-monophosphate dehydrogenase (IMPDH) is a metabolic enzyme that catalyzes the critical step in guanine nucleotide biosynthesis, and thus is at the center of cell growth and proliferation. However, although this enzyme has been exploited as potential target for the development of immunosuppressive, anticancer, and antiviral agents, the functional importance of IMPDH as a promising antiprotozoan drug target is still in its infancy mainly because of the availability of alternative nucleotides metabolic pathways in many of these parasites. This situation suggests that the inhibition of IMPDH might have little to no effect on the survival of protozoan parasites. As a result, no IMPDH inhibitor is currently commercially available or has advanced to clinical trials as a potential antiprotozoan drug. Nevertheless, recent advances toward the development of selective inhibitors of the IMPDH enzyme from Crystosporidium parvum as potential drug candidates against cryptosporidiosis should revive further investigations of this drug target in other protozoa parasites. The current review examines the chemical structures and biological activities of reported protozoan's IMPDH inhibitors. SciFinder was used to broadly pinpoint reports published on the topic in the chemical literature, with no specific time frame. Opportunities and challenges towards the development of inhibitors of IMPDH enzymes from protozoa parasites as potential chemotherapies toward the respective diseases they cause are also discussed.
authors.affiliation: Southeastern Louisiana University, Department of Chemistry and Physics, SLU 10878, Hammond, LA 70402-0878, United States.
authors.forename: Jean
authors.initials: J
authors.lastname: Fotie
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects; D011528:Protozoan Infections / Q000188:drug therapy / Q000469:parasitology / Q000473:pathology; D011684:Purine Nucleosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011741:Pyrimidine Nucleosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014345:Trypanosoma / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D007168:IMP Dehydrogenase
keywords: DNA; Drug target; GMP; IMPDH inhibitors; RNA; nucleotide salvage pathways; protozaon parasites.