ANTI-LEISHMANIA ACTIVITY OF FRAXETIN INDUCES CHANGES IN PROTEOME PROFILE IN LEISHMANIA INFANTUM SPECIES

• DOI: 10.22533/at.ed.12523041212

• Palavras-chave: Atividade antileishmania; Fraxetina; Leishmania infantum; Leishmaniose; Produtos naturais; Proteômica

• Keywords: Anti-leishmania activity; Fraxetine; Leishmania infantum; Leishmaniasis; Natural products; Proteomics

• Abstract: The goal of this study was to evaluate the anti-leishmania activity of fraxetin (6-methoxy-7,8-dihydroxycoumarin) against a strain of Leishmania infantum and to identify possible alterations in the parasite's proteome. Promastigotes forms of L. infantum (2 x 10^6 parasites/mL) were tested with fraxetin at different concentrations (0.195 to 100 µg/mL). Promastigotes were sensitive to fraxetin and we obtained an IC50 of 6.25 µg/mL. To evaluate the effect of the fraxetin, proteomic analysis was performed by LC-MS/MS that identified a total of 1,565 proteins, of which 359 had differences in accumulation after treatment with fraxetin. In particular, 144 proteins were overaccumulated and 215 proteins were downregulated, which could be the result of drug effects on the Leishmania gene expression. For the integration of experimental data, the BlastGO program was used for genetic ontology. Due to the action of fraxetin, the flagellar component of Leishmania seemed to have been affected. According to putative data, 12 proteins involved in the regulation of this important structure were inhibited. Scanning electron microscopy of promastigotes treated with fraxetin showed parasitic aggregations, rounder form with shortened flagella and indicating functional and structural abnormalities. Further studies are needed to consider fraxetin as an anti-leishmania candidate.