Synthesis of Sulfur Compounds for the Treatment of Human African Trypanosomiasis

Human African trypanosomiasis (HAT, also known as African sleeping sickness) is a vector-borne parasitic disease transmitted by the tsetse fly. The two forms of the disease (of which each has two stages) are caused by protozoan members of the Trypanosoma genus. If left untreated, HAT is usually a fatal disease; the infection gradually progresses to a coma, then severe organ failure, and eventually death.1 There are several major health and administrative difficulties in treating HAT. Of the four drugs that are currently in use, melarsoprol is arsenic-based and as such is highly toxic, causing fatal reactive encephalopathy in 10% of patients.2 Pentamidine is ineffective against stage II Trypanosoma brucei gambiense and suramin is ineffective against both stage II T. b. gambiense and stage II T. b. rhodesiense. In the second stage of the disease, eflornithine has to be administered as 56 infusions over a 14 day period. It has low efficacy against T. b. rhodesiense. In addition, two kits for an eflornithine monotherapy weigh 40 kg and cost US$1,420.3 Trypanosomal drug resistance has also been observed with leading treatment drugs melarsoprol and eflornithine.4,5 Given that there presently does not exist a low-toxicity and practical treatment for HAT, and the trypanosomes are becoming increasingly resistant to current drugs, research regarding the synthesis of novel compounds is needed