One of the most neglected disease is the Sleeping sickness or Human African Trypanosomiasis
(HAT), which is mostly restricted to poor regions of Africa. The disease is caused by
parasitic infection with Trypanosoma brucei (T. brucei), and is acquired through the bite of the tsetse
fly. In the first stage of the disease, the parasite is in the blood, but in stage 2, the infective form
reaches the brain, causing great weakness and death. The few existing drugs against this infection, are
highly toxic, and can cause the emergence of resistant forms of the parasite. Also, these drugs are not
readily available. New drugs are needed. Many researchers are investigating new enzyme targets for the parasite, searching
for more efficient and selective inhibitors that are capable to cause the parasite death with less toxicity to the host.
Trypanothione reductase, farnesyl diphosphate synthase, 6-phospho-gluconate dehydrogenase, and UDP 4'-galactose epimerase
are some of the enzymes involved in the studies reported on this review. In addition, we have applied ligandbased-
virtual screening, using Random Forest associated with structure-based-virtual screening (docking), to a small
dataset of 225 alkaloids from the Menispermaceae family (in-house data bank). The aim of this study is to select structures
with potential inhibitory activity against trypanothione reductase from Trypanosoma brucei. The computer-aided
drug design study selected certain alkaloids that might be worth further investigation.