An Insight into the Discovery of Potent Antifilarial Leads Against Lymphatic Filariasis.

BACKGROUND AND OBJECTIVES: Lymphatic filariasis is a neglected tropical disease caused by infection with filarial worms that are transmitted through mosquito bites. Globally, 120 million people are infected, with nearly 40 million people disfigured and disabled by complications such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). Current treatments (ivermectin, diethylcarbamazine) have limited effects on adult parasites and produce side effects; therefore, there is an urgent to search for new antifilarial agents. Numerous studies on the antifilarial activity of pure molecules have been reported accross the recent literature. The present study describes the current standings of potent antifilarial compounds against lymphatic filariasis. METHODS: A literature search was conducted for naturally occurring and synthetic antifilarial compounds by referencing textbooks and scientific databases (SciFinder, PubMed, Science Direct, Wiley, ACS, SciELO, Google Scholar, and Springer, among others) from their inception until September 2019. RESULTS: Numerous compounds have been reported to exhibit antifilarial acitivity in adult and microfilariae forms of the parasites responsible for lymphatic filariasis. In silico studies of active antifilarial compounds (ligands) showed molecular interactions over the protein targets (trehalose-6-phosphate phosphatase, thymidylate synthase, among others) of lymphatic filariasis, and supported the in vitro results. CONCLUSION: With reference to in vitro antifilarial studies, there is evidence that natural and synthetic products can serve as basic scaffolds for the development of antifilarial agents. The optimization of the most potent antifilarial compounds can be further performed, followed by their in vivo studies.

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

BACKGROUND: 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. OBJECTIVE: The present review summarizes the current standings and perspectives for the use of flavonoids as lead compounds for the potential treatment of HAT. METHODS: 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. RESULTS: 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. CONCLUSION: 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.