Inhibitors of dihydrofolate reductase in Leishmania and trypanosomes.
The protozoan diseases leishmaniasis, Chagas' disease and African trypanosomiasis are major health problems in many countries, particularly developing countries, and there are few drugs available to treat these diseases. Dihydrofolate reductase (DHFR) inhibitors have been used successfully in the treatment of a number of other diseases such as cancer, malaria and bacterial infections; however they have not been used for the treatment of these diseases. This article summarises studies on leishmanial and trypanosomal DHFR inhibitor development and evaluation. Possible mechanisms of resistance to DHFR inhibitors are also discussed.
Gilbert
Ian H
IH
Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, UK. gilbertih@cf.ac.uk
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy; D015195:Drug Design; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology; D007896:Leishmaniasis / Q000188:drug therapy; D008958:Models, Molecular; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects* / Q000201:enzymology; D014353:Trypanosomiasis, African / Q000188:drug therapy
D005493:Folic Acid Antagonists; D014344:Trypanocidal Agents; D013762:Tetrahydrofolate Dehydrogenase