Potential of ethyl acetate and acetone extracts from Montrichardia linifera leaves: Chemical characterization, in vitro study, molecular docking and ADME-TOX

Leishmaniasis is a neglected tropical disease that affects millions of people worldwide, and current treatments are limited by toxicity and increasing parasite resistance, highlighting the need for new therapeutic agents. Montrichardia linifera, a plant used in traditional medicine, has shown relevant antiparasitic potential. This study evaluated the antileishmanial activity of acetone (EAMl), ethyl acetate (EAEMl), and ethanolic (EEMl) extracts of M. linifera. Chemical characterization was performed by liquid chromatography-mass spectrometry (LC-MS), and complementary in silico ADME/Tox predictions and molecular docking analyses were conducted. Antileishmanial activity was assessed against Leishmania (L.) major promastigotes using the MTT assay, and ultrastructural alterations were analyzed by atomic force microscopy (AFM). LC-MS results showed that EAEMl was the most chemically diverse extract, with quercetin identified as a major constituent. EAEMl exhibited the highest antipromastigote activity, with an IC₅₀ value of 20.30 μg/mL. AFM analysis revealed severe morphological damage in treated parasites, including membrane disruption and cell retraction. In silico analyses indicated favorable pharmacokinetic profiles for the main compounds. Molecular docking identified corilagin as the compound with the strongest affinity for pteridine reductase 1 (PTR1; PDB ID: 1E7W), with a binding energy of -10.9 kcal/mol. Overall, these findings demonstrate that M. linifera extracts, particularly those rich in phenolic compounds, exhibit promising antileishmanial activity, supporting their potential as sources of new therapeutic candidates.