Also known as sleeping sickness, human African trypanosomiasis (HAT) is
caused by protozoan parasites of the genus Trypanosoma transmitted between humans
by the bites of tsetse flies (glossina). HAT is caused by two parasite subspecies -
Trypanosoma brucei gambiense (accounting for 92% of reported cases and causes
chronic illness) and Trypanosoma brucei rhodesiense (accounting for 8% of reported
cases and is responsible for the acute form of the disease). The former can advance,
affecting the central nervous system, while the latter can develop rapidly with multiple
organs, including the brain, being invaded. If left untreated, HAT is generally fatal.
According to the World Health Organization, in the period 2016 – 2020, about 55
million people were at risk of infection, with nearly 1000 cases reported in 2018.
Current treatment options have limitations such as complex administration procedures,
limited effectiveness, emergence of drug resistance, and undesirable side effects.
Therefore, new drugs are required. In this book chapter, we summarize current efforts
aimed at identifying new drug candidates and their corresponding mechanisms of
action. We highlight medicinal chemistry optimization efforts for different candidates
while giving detailed insights into the mechanism of function for the corresponding
drug targets. Such information is of value as it equips drug discovery scientists with
information about chemical modifications, which can lead to improvement in certain
physicochemical and biological properties of new chemical entities.
Keywords: HSPs, HAT, MAPKs, Protein tyrosine kinases, Rhodesain, Sleeping sickness, T. b. gambiense, T. b. rhodesiense.
