Title:The Role of Flavanones as Scaffolds for the Development of New Treatments
against Malaria and African and American Trypanosomiases
Volume: 23
Issue: 14
Author(s): Pone Kamdem Boniface*, Elizabeth Igne Ferreira and Fekam Boyom Fabrice
Affiliation:
- Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Laboratory for Phytobiochemistry and Medicinal Plants Study, Department of Biochemistry, Faculty of Science, University
of Yaoundé 1; P.O. Box 812, Yaoundé, Cameroon
Keywords:
Flavanones, tropical diseases, parasite, malaria, trypanosomiases, lead compounds.
Abstract: Parasitic infections are diseases transmitted by parasites usually found in contaminated
food, water, or insect bites. Generally classified as neglected tropical diseases, malaria and trypanosomiases
are some of the most prominent parasitic diseases that cause significant loss of life annually.
In 2020, an estimated 241 million malaria cases were reported, with 627,000 deaths worldwide. An
estimated 6 to 7 million people are infected with Trypanosoma cruzi worldwide, whereas an estimated
1000 global cases of African human trypanosomiasis were reported in 2020. Flavanones are a group of
compounds that belong to the flavonoid family and are chemically obtained by direct cyclization of chalcones.
Recent pharmacological studies have demonstrated the effectiveness of plant flavanones in inhibiting
the growth of the parasites responsible for malaria and trypanosomiases. The present work aims to
summarize up-to-date and comprehensive literature information on plant flavanones with antimalarial
and antitrypanosomal activities. The mechanisms of action of the antiparasitic flavanones are also discussed.
A literature search was performed for naturally occurring flavanones and antimalarial and antitrypanosomal
activities by referencing textbooks and scientific databases (SciFinder, Wiley, American
Chemical Society, Science Direct, National Library of Medicine, Scientific Electronic Library
Online, Web of Science, etc.) from their inception until April 2022. Based on in vitro experiments,
more than sixty flavanones were reported to exhibit antimalarial, anti-T. cruzi, and anti-T. brucei activities.
Previous studies demonstrated that these compounds bind to PGP-like transporters of P. falciparum
to reverse the parasite’s resistance. Other reports pinpointed the direct effect of these compounds
on the mitochondria of the malaria parasite. Moreover, flavanones have shown strong docking
to several validated T. cruzi and T. brucei protein targets, including adenosine kinase, pteridine reductase
1, dihydrofolate reductase, and trypanothione reductase, among others. Flavanones, isolated and
characterized from diverse plant parts, were reported to exhibit moderate to high activity against P.
falciparum, T. cruzi, and T. brucei in in vitro studies. These potentially active flavanones can be used
as scaffolds for the development of new antiparasitic agents. However, more studies on the cytotoxicity,
pharmacokinetics, and mechanisms of action of potent flavanones should be performed.