In Vitro and In Silico Evaluation of the Leishmanicidal and Trypanocidal Activities of Lignan Methylpiperitol Isolated from Persea Fulva

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Reis, Isabella Mary Alves ; da Silva, Girliane Regina ; de Mattos Oliveira, Larissa ; dos Santos Jr, Manoelito Coelho ; da Silva, Tania Maria Sarmento ; Vieira, Ivo Jose Curcino ; Braz-Filho, Raimundo ; Romanelli, Maiara Maria ; Amaral, Maiara ; Tempone, Andre Gustavo ; Lago, Joao Henrique Ghilardi ; Branco, Alexsandro

• Document type: Journal article
• Source: CHEMISTRY & BIODIVERSITY; v. 21, n. 8, p. 7-pg., 2024-07-31.

Abstract

Neglected Tropical Diseases are a significant concern as they encompass various infections caused by pathogens prevalent in tropical regions. The limited and often highly toxic treatment options for these diseases necessitate the exploration of new therapeutic candidates. In the present study, the lignan methylpiperitol was isolated after several chromatographic steps from Persea fulva L. E. Koop (Lauraceae) and its leishmanicidal and trypanocidal activities were evaluated using in vitro and in silico approaches. The chemical structure of methylpiperitol was defined by NMR and MS spectral data analysis. The antiprotozoal activity of methylpiperitol was determined in vitro and indicated potency against trypomastigote forms of Trypanosoma cruzi (EC(50 )of 4.5 +/- 1.1 mM) and amastigote forms of Leishmania infantum (EC50 of 4.1 +/- 0.5 mM), with no mammalian cytotoxicity against NCTC cells (CC50>200 mM). Molecular docking studies were conducted using six T. cruzi and four Leishmania. The results indicate that for the molecular target hypoxanthine phosphoribosyl transferase in T. cruzi and piteridine reductase 1 of L. infatum, the methylpiperitol obtained better results than the crystallographic ligand. Therefore, the lignan methylpiperitol, isolated from P. fulva holds potential for the development of new prototypes for the treatment of Neglected Tropical Diseases, especially leishmaniasis. (AU)

• FAPESP's process: 23/12447-1 - Searching for specialized metabolites from Brazilian floristic biodiversity as drug candidates for neglected tropical diseases
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants