Accession Number : ADA192131

Title :   Chemotherapy and Biochemistry of Leishmania.

Descriptive Note : Final rept. 1 Oct 81-31 Dec 86,

Corporate Author : MASSACHUSETTS UNIV AMHERST

Personal Author(s) : Nolan, Linda L

PDF Url : ADA192131

Report Date : 30 Jan 1987

Pagination or Media Count : 30

Abstract : The overall aim of this research for the last five years has been to determine the mode of action of promising antileishmanial agents for the purpose of rational drug development. Enzymatic differences and requirements between the synthesis of nucleic acids in the parasite and host were studied for the purpose of chemotherapeutic exploitation. 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. Sinefungin has been found to be a potent antiparasitic agent at levels which are non-toxic to mammalian cells. Our laboratory has found that it drastically affects DNA synthesis in Leishmania spp. We are currently investigating its exact mode of action, to aid in rational drug development.

Descriptors :   *ANTIPARASITIC DRUGS, *BIOCHEMISTRY, *BIOSYNTHESIS, *CHEMOTHERAPY, *LEISHMANIA, *MEDICAL RESEARCH, CELLS(BIOLOGY), DEOXYRIBONUCLEIC ACIDS, DRUGS, ENZYMES, KINETOPLAST, MAMMALS, METABOLISM, NUCLEIC ACIDS, NUCLEOTIDES, POTENCY, PURINES, TOXICITY, SYNTHESIS(CHEMISTRY)

Subject Categories : Microbiology
      Pharmacology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE