Exploring the selective incorporation of 15β-senecioyloxi-ent-kaurenoic acid methyl ester in Langmuir monolayers mimicking cell membranes

Author(s)

da Silva, Gustavo H. O. ; dos Santos, Kevin F. ; Barcellos, Aline F. ; de Sousa, Raquel M. Ferreira ; Tempone, Andre G. ; Lago, Joao Henrique G. ; Caseli, Luciano

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 153, p. 12-pg., 2024-12-01.

Abstract

A natural product isolated from Brazilian plant species Baccharis retusa (Asteraceae), 15(3-senecioyloxi-entkaurenoic acid (1), demonstrated activity against trypomastigotes of the parasite Trypanosoma cruzi but it was inactive against intracellular forms. In the present work, compound 1a, a methyl ester derivative of 1, exhibited activity against intracellular amastigotes (EC50 = 11.8 mu M), similar to that determined by the standard drug benznidazol (EC50 = 16.2 mu M) and no toxicity against NCTC cells (CC50 > 200 mu M). Based on this selectivity, compound 1a was incorporated into Langmuir monolayers of three lipids, DPPC, DPPE, and DPPS, to characterize the interaction of the compound with each lipid as model for cell membranes. For that, we used tensiometry, surface potential measurements, and infrared spectroscopy. Our results showed that incorporating the drug into DPPC monolayers significantly altered the physicochemical properties, resulting in more condensed monolayers. In contrast, the incorporation of the drug into DPPE and DPPS monolayers led to their expansion. The effects on DPPC were more pronounced than on the other lipids, inducing a viscoelastic monolayer with lower alignment of the alkyl chains, as observed through surface potential measurements and infrared spectroscopy. These changes indicate a more cohesive DPPC monolayer upon drug incorporation, forming domains in a strip shape. We believe these results contribute to understanding the interaction between 1a and lipid interfaces, especially those involved in biological interactions with amastigotes of parasite T. cruzi. (AU)

• FAPESP's process: 18/22214-6 - Towards a convergence of technologies: from sensing and biosensing to information visualization and machine learning for data analysis in clinical diagnosis
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Research Projects - Thematic Grants
• 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: 22/03736-7 - Nanostructured interfaces for the investigation of bioactive substances in cell membrane models and for the construction of optoelectronic devices
• Grantee: Luciano Caseli
• Support Opportunities: Regular Research Grants