Targeting DHFR in parasitic protozoa.
Parasitic apicomplexans are responsible for some of the most severe worldwide health problems, including malaria, toxoplasmosis and cryptosporidiosis. These parasites are characterized by a bifunctional enzyme, dihydrofolate reductase-thymidylate synthase (DHFR-TS), which has a crucial role in pyrimidine biosynthesis. Inhibitors of DHFR have been successful in the treatment of toxoplasmosis and malaria. However, there is currently no effective therapy for cryptosporidiosis, and despite early successes against malaria, resistance to DHFR inhibitors in malaria parasites has now become a global problem. Novel DHFR inhibitors, designed using the recently revealed crystal structures of the enzymes from two parasitic protozoa, are in development.
Anderson
Amy C
AC
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA. Amy.C.Anderson@Dartmouth.edu
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D056890:Eukaryota / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D005493:Folic Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D011528:Protozoan Infections / Q000188:drug therapy* / Q000201:enzymology; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*
D000981:Antiprotozoal Agents; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase