| The overall objective of this research is to develop new chemotherapeutic approaches for the treatment of parasitic protozoan diseases. The work presented in this thesis focuses on the design, synthesis, and screening (in vitro and in vivo) of bisphosphonates as a novel class of anti-parasitic agents. The infectious agents targeted in this study are Trypanosoma brucei, Trypanosoma cruzi, Toxoplasma gondii, Leishmania spp., and Plasmodium falciparum. These parasites are responsible for African sleeping sickness, South American trypanosomiasis (Chagas' disease), toxoplasmosis, leishmaniasis, and malaria, respectively. The studies contained within this thesis were carried out in three main areas: (a) demonstration of selective anti-parasitic activity of bisphosphonates, (b) elucidation of molecular mechanism and identification of the molecular parasitic target of bisphosphonates, and (c) enhancement of bisphosphonate activity through rational drug design. All of the findings reported in this volume suggest that bisphosphonates appear to be a promising class of compounds for the development of new drugs effective in the treatment of parasitic diseases. |
