Antiprotozoal/Antiparasitic Agents

Abstract

Collectively, diseases caused by parasitic protozoa, including human African trypanosomiasis (HAT), Chagas' disease and leishmaniasis, threaten more than 550 million people worldwide and cause nearly 150,000 deaths annually. The causative organisms for these diseases are unicellular trypanosomatid parasites of the genera Trypanosoma brucei, Trypanosoma cruzi, and Leishmania sp., respectively. Drug therapies available for these diseases have not changed significantly in the past 50 years, and currently used agents are far less than satisfactory due to extreme toxicity, and because resistant parasitic strains are becoming more prevalent. These diseases are confined to impoverished or rural areas of Mexico, Central America, South America, sub-Saharan Africa, the Middle East, Indonesia, and India. As such, drug discovery efforts against trypanosomatid diseases are limited because patients in underdeveloped areas cannot afford therapy, and because the infected population is too small to justify the required research expenditures. In addition, antiparasitic research in Third World nations is often hampered by economic issues and political turmoil, virtually assuring that the world's most impoverished people will continue to bear the major burden of parasitic disease. Clearly, there is a need for new anti-infective agents that are potent, nontoxic and inexpensive to manufacture. In this chapter, the etiology of these diseases and their current treatment are described. The chapter also deals with medicinal chemistry aspects of efforts to identify new drug targets for parasitic diseases, and to produce novel inhibitors of trypanosomatid growth for use as antiparasitic agents. Keywords: amidine; antiparasitic; Chaga's disease; chemotherapy; cutaneous leishmaniasis; cysteine protease; glucose metabolism; glucose transport; glycosome; guanidine; human African trypanosomiasis; Leishmania donovani; life cycle; lipid metabolism; nucleotide transporter; polyamines; protozoa; Trypanosoma brucei; Trypanosoma cruzi; visceral leishmaniasis