The anti-Leishmania potential of bioactive compounds derived from naphthoquinones and their possible applications. A systematic review of animal studies

Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti- Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti- Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti- Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th 1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments. Graphical abstract