Flavonoid-derived Privileged Scaffolds in anti-Trypanosoma brucei Drug Discovery.

Abstract

Human African Trypanosomiasis (HAT), also known as sleeping sickness is one of the 20 neglected tropical diseases listed by the World Health Organization, which lead to death if left untreated. This disease is caused by Trypanosoma brucei gambiense, which is the chronic form of the disease present in western and central Africa, and by T. brucei rhodesiense, which is the acute form of the disease located in eastern and southern Africa. Many reports have highlighted the effectiveness of flavonoid-based compounds against T. brucei. The present review summarizes the current standings and perspectives for the use of flavonoids as lead compounds for the potential treatment of HAT. A literature search was conducted for naturally occurring and synthetic anti-T brucei flavonoids by referencing textbooks and scientific databases (SciFinder, PubMed, Science Direct, Wiley, ACS, SciELO, Google Scholar, Springer, among others) from their inception until February 2019. Flavonoids isolated from different parts of plants and species were reported to exhibit moderate to high in vitro antitrypanosomal activity against T. brucei. In addition, synthetic flavonoids revealed anti-T. brucei activity. Molecular interactions of bioactive flavonoids with T. brucei protein targets showed promising results. According to in vitro anti-T brucei studies, there is evidence that flavonoids might be lead compounds for the potential treatment of HAT. However, toxicological studies, as well as the mechanism of action of the in vitro active flavonoids are needed to support their use as potential leads for the treatment of HAT.