Leishmanicidal Potential of Eugenia pyriformis Cambess. (Myrtaceae) Leaf Extracts: Metabolomics and Mechanism of Action.

Developing new therapies and discovering bioactive compounds to treat cutaneous leishmaniasis are critical to improving patients' quality of life. More effective, less toxic, and affordable compounds are needed. Thus, discovering such compounds could significantly enhance the management and control of cutaneous leishmaniasis. Brazil has a biodiversity of flora and microorganisms that remains unexplored, mainly for evaluating extracts and compounds with anti-Leishmania activity. This study aimed to screen the leishmanicidal activity of extracts and fractions from leaves of Eugenia pyriformis Cambess. collected during different seasons (winter and summer) in Rio de Janeiro, Brazil. Extracts from summer-collected leaves showed higher effectiveness against Leishmania (Leishmania) amazonensis promastigotes and amastigotes. The IC50 values for the extract from leaves collected in summer (Ep1) were significantly lower than those for winter extracts. Extracts showed low toxicity to human macrophages and a high selectivity index (SI > 12). In addition, the Ep1 extract induced G0/G1 phase arrest and necrosis in promastigotes. UHPLC-HR-ESI-MS/MS analysis combined with molecular networking revealed that flavonoids and terpenoids were predominant in active fractions. The study highlights the potential of E. pyriformis Cambess. as a source of leishmanicidal compounds from leaves collected during the summer season.