Anti-Trypanosoma cruzi Effect of Fatty Acids from Porcelia macrocarpa Is Related to Interactions of Cell Membranes at Different Microdomains as Assessed Using Langmuir Monolayers

Author(s)

Brito, Ivanildo A. ; Rosa, Matheus E. ; Boisselier, Elodie ; Albuquerque, Vanessa ; Tempone, Andre G. ; Caseli, Luciano ; Lago, Joao Henrique G.

• Document type: Journal article
• Source: ACS OMEGA; v. 10, n. 21, p. 8-pg., 2025-05-21.

Abstract

Chagas disease, a parasitic disease caused by the protozoan Trypanosoma cruzi, is an important health problem affecting more than 8 million people worldwide. The only available treatments, benznidazole and nifurtimox, display high toxicity and reduced efficacy in the chronic phase of the disease. To find new natural products with anti-T. cruzi activity, the CH2Cl2 extract of Porcelia macrocarpa R. E. Fries (Annonaceae) seeds was subjected to bioactivity-guided fractionation. Through several chromatographic steps, one group consisting of a mixture of 10 chemically related fatty acids (1-10) was obtained. This group showed activity against trypomastigote forms with an EC50 of 4.0 mu g/mL, similar to the standard drug benznidazole (EC50 = 3.9 mu g/mL). It also showed activity against the intracellular amastigotes, with an EC50 of 0.5 mu g/mL, close to the efficacy of benznidazole (EC50 = 0.9 mu g/mL). In addition, the mixture of 1-10 showed no toxicity against murine fibroblasts (CC50 > 200 mu g/mL), resulting in SI > 49 and >416 in trypomastigotes and amastigotes, respectively. The interaction of the mixture with the protozoan membrane models was also assessed with Langmuir monolayers composed of three phosphatidylethanolamine (PE) lipids with different degrees of acyl chain unsaturation and in the presence of mucins. Compounds 1-10 favorably interact with all tested lipids, with maximum insertion pressure (MIP) values above 40 mN/m and positive synergy values, suggesting penetration through the mucins. Furthermore, the mixture has a higher affinity for monounsaturated lipids bound to mucins, with an MIP value of 57.59 +/- 2.59 mN/m. Based on these results, the effect of compounds 1-10 against T. cruzi can be related to interactions with the parasite cell membranes. (AU)

• FAPESP's process: 23/12475-5 - Systematizing chiroptical properties of lignans: implications for correct absolute configuration assignments
• Grantee: João Marcos Batista Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/15084-1 - Interaction of natural acetogenins with biological activity in membrane models at the air-water interface
• Grantee: Matheus Elias Rosa
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• 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
• FAPESP's process: 23/16020-2 - Studying the interaction of antiprotozoal acetogenins with membrane models utilizing mixed Langmuir films of lipids and mucins
• Grantee: Matheus Elias Rosa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 19/22319-5 - Vibrational circular dichroism spectral markers: facilitating absolute configuration assignment of natural products
• Grantee: João Marcos Batista Junior
• Support Opportunities: Regular Research Grants