The long term objective of this project is to identify and to study novel chemotherapeutic approaches to the control of leishmanial and trypanosmal infections of substantial medical importance, by exploiting new knowledge that aspects of the lipid biochemistry of the responsible trypanosomatid flagellates are characteristic of fungi and not of vertebrates. The immediate specific aims to realize this objective are to investigate: a) the normal sterol metabolism of the life-cycle stages of representative species of Leishmania and Trypanosoma, b) the perturbations of that metabolism, and impairment of growth, caused by hypercholesterolemic and other cytotoxic drugs, and c) the mechanisms of action of the most effective of those drugs. Life-cycle stages are to be cultured in vitro, exposed to drugs, and the consequences to growth and to lipid metabolism assessed by population enumeration, and by lipid analysis employing chromatographic (CC, TLC, HPLC, GLC), spectrometric (GC/MS, 1H and 13C NMR, UV/VIS, FTIR), and radio- and stable isotopic tracer methodologies.
