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Unsaturated lipids modulating the interaction of the antileishmanial isolinderanolide E with models of cellular membranes

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Author(s):
Rosa, Matheus Elias ; Conserva, Geanne A. Alves ; Passero, Luiz Felipe D. ; Lago, Joao Henrique G. ; Caseli, Luciano
Total Authors: 5
Document type: Journal article
Source: BIOORGANIC CHEMISTRY; v. 124, p. 7-pg., 2022-07-01.
Abstract

The present work evaluated the antiprotozoal activity of isolinderanolide E, isolated from the Brazilian plant Nectandra oppositifolia, against promastigote forms of Leishmania (Leishmania) amazonensis. The compound exhibited an EC50 value of 20.3 mu M, similar to the positive control miltefosine (IC50 of 19.4 mu M), and reduced toxicity to macrophages (CC50 > 200 mu M). Based on these results, Langmuir monolayers of two unsaturated lipids: 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), were employed as a model of mammalian and parasite membranes, respectively, to study the interaction of isolinderanolide E at a molecular level. The films were characterized with tensiometry (surface pressure-area isotherms and surface pressure-time curves), infrared spectroscopy, and Brewster angle microscopy (BAM). This compound changed the profile of the isotherms leading to fluid DOPC and DOPE monolayers, which were not able to attain rigid states even with compression. Infrared spectroscopy showed that the bioactive compound decreases the trans/gauche ratio conformers related to the molecular conformational disorder. BAM showed the formation of specific aggregates upon drug incorporation. In conclusion, isolinderanolide E changes the thermodynamic, mechanical, structural, and morphological characteristics of the monolayer of these unsaturated lipids, which may be essential to understand the action at the molecular level bioactives in biointerfaces. (AU)

FAPESP's process: 21/02789-7 - Search for bioactive metabolites with antiparasitic action in plant species from Atlantic Forest and Cerrado regions - a chemical, phenotypical, and metabolomic approach
Grantee:João Henrique Ghilardi Lago
Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
FAPESP's process: 19/04407-4 - Study of the surface activity of alkylated lactones and their interaction in cell membrane models
Grantee:Matheus Elias Rosa
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/20633-6 - Bioactive metabolites from Nectandra oppositifolia Nees & Mart. (Lauraceae): molecular characterization, in vitro and in vivo antiparasitic potential evaluation and determination of mechanism of action
Grantee:Geanne Alexsandra Alves Conserva
Support Opportunities: Scholarships in Brazil - Doctorate
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: 18/24077-6 - Pre-clinical studies of non-invasive treatments in leishmaniasis
Grantee:Luiz Felipe Domingues Passero
Support Opportunities: Regular Research Grants
FAPESP's process: 19/03239-0 - 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