Browsing by Author "Muganza, Freddy Munyololo"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Open Access
    Ferrocenic metal chelators : synthesis, biological and electrochemical studies
    (2006) Muganza, Freddy Munyololo; Chibale, Kelly; Hutton, Allan T
    Resistance of Plasmodium falciparum (P. falciparum) to well-established drugs throughout the world has necessitated urgent alternative treatment for malaria. Iron chelation therapy was considered as a possible approach since iron has been found crucial in the metabolic pathways of P. falciparum. A series of novel iron chelators were designed and synthesized based on thiosemicarbazone and/or ferrocenyl moieties. The novel compounds were characterized by NMR, infrared (IR) and mass spectroscopy as well as microanalysis and subjected to biological evaluation. All the N-substituted ferrocenic thiosemicarbazones were evaluated against a chloroquine resistant W2 strain of the malaria parasite P. falciparum and enzymes (falcipains 2 & 3) derived from the same parasite. The intermediate thiosemicarbazone thioesters were also tested against different malaria parasite including chloroquine resistant (K1) and chloroquine sensitive (307) strains as well as against the causative agent of African trypanosomiasis, Trypanosoma brucei (T. brucei). Of the intermediate thiosemicarbazone thioesters, compound 44y a bipyridyl compound was the most active against both K1 and 307 strains with ED50 values of 0.18 /lg/ml (0.625 /lM) and 0.021 /lg/ml (0.072 /lM), respectively. However, this compound 44y also showed similar toxicity to mammalian cells. A number of thiosemicarbazone thioesters displaying preferential potency against a chloroquine resistant (K1) strain were noted. For example, compounds 44a-h, 44k-m, 445, 44u-v were found to be more active against K1 than against the chloroquine sensitive (307) strain.
  • Thumbnail Image
    Item
    Open Access
    New synthetic routes to functionalized 2-C-alkylglucosides, precursors of potential inhibitors of mycothiol biosynthesis in the Mycobacteria
    (2011) Muganza, Freddy Munyololo; Gammon, David W
    This thesis was concerned with the design and synthesis of compounds which are either substrate-mimics or inhibitors of MshB, a N-deacetylase involved in the biosynthesis of mycothiol in the Mycobacteria, including M. tuberculosis, the causative agent of TB. Mycothiol is a low molecular weight thiol produced by Mycobacteria as a defense against oxidative stress and xenobiotics, and the enzymes involved in its biosynthesis are postulated to be viable drug targets.