Chemotherapy for Chagas' disease: a perspective of current therapy and considerations for future research.
Our current knowledge of the biology of Trypanosoma cruzi and its relation to the development of chemotherapy for Chagas' disease are reviewed. This includes recent developments in the understanding of kinetoplast DNA and glycosomes; the action of oxygen radicals; intermediary metabolism of purines, pyrimidines, and folic acid; and the formation of microtubules. At this time, these organelles and metabolic pathways appear to be the most promising for potential exploitation for chemotherapeutic purposes. Compounds of current experimental interest also are discussed. These are agents that have shown promise in the laboratory and for which data exist regarding probable mechanisms of action. The activities of these agents correlated, in so far as is possible, with those structures or metabolic pathways in the trypanonsome that are affected by their actions. The compounds are of two general groups: nitro compounds and purine analogues.
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D004261:DNA Replication; D004270:DNA, Circular / Q000235:genetics; D018105:DNA, Kinetoplast; D006801:Humans; D008830:Microbodies / Q000201:enzymology; D008870:Microtubules / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure
D004270:DNA, Circular; D018105:DNA, Kinetoplast; D011687:Purines; D011743:Pyrimidines; D014344:Trypanocidal Agents; D010100:Oxygen