Accession Number : ADA192132

Title :   Chemotherapy and Biochemistry of Leishmania.

Descriptive Note : Annual rept. 1 Jan-31 Dec 86,

Corporate Author : MASSACHUSETTS UNIV AMHERST

Personal Author(s) : Nolan, Linda L

PDF Url : ADA192132

Report Date : Dec 1986

Pagination or Media Count : 41

Abstract : A comparison of the enzymes of the pathogenic protozoa to those of man is of fundamental importance to the search for much needed chemotherapeutic agents. Nucleic acid metabolism in trypanosomatids is unique in several ways: (1) they lack the ability to synthesize purines de novo, depending entirely on the salvage pathway for their supply of purine nucleotides; (2) many of the enzymes involved in nucleic acid biosynthesis either have unusual substrate specificities or unusual subcellular localizations; (3) a large proportion of the DNA which is produced is incorporated into a unique organelle known as the kinetoplast; and (4) the DNA polymerase isolated from these organisms demonstrates major differences from its mammalian counterpart. Our aim has been the isolation and characterization of the DNA and RNA polymerase of Leishmania mexicana and search in vivo and in vitro for inhibitors of these enzymes for chemotherapeutic exploitation. Sinefungin has been shown to inhibit the development of various fungi and viruses, but its major attraction to data resides in its potent antiparasitic activity. This compound has been reported to display antiparasitic activity against malarial, trypanosoma, and leishmanial species. We found that sinefungin was significantly suppressive against both Leishmania donovani and L. braziliensis panamensis infections in hamsters when compared to glucantime.

Descriptors :   *ANTIPARASITIC DRUGS, *BIOCHEMISTRY, *CHEMOTHERAPEUTIC AGENTS, *LEISHMANIA, *MEDICAL RESEARCH, BIOSYNTHESIS, CHEMOTHERAPY, COMPARISON, DEOXYRIBONUCLEIC ACIDS, ENZYMES, FUNGI, HAMSTERS, IN VITRO ANALYSIS, IN VIVO ANALYSIS, ISOLATION, KINETOPLAST, METABOLISM, NUCLEIC ACIDS, NUCLEOTIDES, PATHOGENIC MICROORGANISMS, POTENCY, PROTOZOA, PURINES, SEARCHING, TRYPANOSOMA, VIRUSES, SYNTHESIS(CHEMISTRY)

Subject Categories : Medicine and Medical Research
      Microbiology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE