Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface

Author(s)

Barbosa, Henrique ^[1] ; da Silva, Rafael Leonardo C. G. ^[2] ; Costa-Silva, Thais A. ^[1] ; Tempone, Andre G. ^[3] ; Antar, Guilherme M. ^[4] ; Lago, Joao Henrique G. ^[1] ; Caseli, Luciano ^[2]

Affiliation

^[1] Fed Univ ABC, Ctr Nat & Human Sci, Santo Andre, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Chem, Diadema, SP - Brazil

^[3] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Inst Biosci, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 101, AUG 2020.
• Web of Science Citations: 5

Abstract

In the present work, the oxoaporphine alkaloid dicentrinone was isolated, for the first time, from leaves of Ocotea puberula (Lauraceae). This alkaloid exhibited antiparasitic activity against trypomastigote forms of Trypanosoma cruzi (IC50 of 16.4 +/- 1.7 mu M), similar to the positive control benznidazole (IC50 of 18.7 +/- 4.1 mu M), reduced mammalian cytotoxicity (CC50 > 200 mu M), and a selectivity index (SI) higher than 12. These results were correlated with the effects observed using cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero- 3-phosphoethanolamine (DPPE), in Langmuir monolayers. Dicentrinone was incorporated in the films, sub-mitted to lateral compression, and characterized by tensiometry. As observed in compression-decompression and time-stability curves, dicentrinone expanded the lipid monolayers, decreased the compressional modulus of the film, and reduced the stability of the monolayer. Brewster Angle Microscopy and interfacial Infrared Spectroscopy showed that dicentrinone causes the monolayers to be segregated in phases, and to increase the number of gauche/trans conformers ratio for the lipid acyl methylene groups, indicating configurational disorder. As a result, dicentrinone caused a disturbance in the cell membrane models, altering the physicochemical properties of the lipid surface such as thermodynamic, rheological, morphological, and structural aspects. These results can be useful to understand the interactions between dicentrinone and lipid biological surfaces at the molecular level. (AU)

• FAPESP's process: 18/00291-9 - Langmuir and Langmuir-Blodgett films of lipids containing phenylalanine dehydrogenase for sensors of phenylalanine
• Grantee: Rafael Leonardo Cruz Gomes da Silva
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
• Grantee: André Gustavo Tempone Cardoso
• Support type: 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 type: Regular Research Grants
• FAPESP's process: 18/07885-1 - Biomolecules from plant species of remnant areas of the Atlantic Forest and Cerrado to treat neglected tropical diseases - chemical and pharmacological aspects
• Grantee: João Henrique Ghilardi Lago
• Support type: BIOTA-FAPESP Program - Regular Research Grants