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Evaluation and comparison of the trypanocidal effects of benzofuroxan active derivatives on giant synthetic vesicles (GUVs)containing ergosterol.

Grant number: 15/25062-4
Support Opportunities:Scholarships abroad - Research
Effective date (Start): April 11, 2016
Effective date (End): June 25, 2016
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Regina Maria Barretto Cicarelli
Grantee:Regina Maria Barretto Cicarelli
Host Investigator: Gregor Gomiscek
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Research place: University of Ljubljana (UL), Slovenia  


Chagas disease is endemic in America. Currently, the most widely used drug inBrazil is benznidazole, whose action is limited according to the stage of the disease, thestrain of Trypanosoma cruzi and severe side effects. The staff of the applicant incollaboration with other research groups (NuBBe-IQAr and Lapdesf-FCFAr both fromUNESP) held trypanocidal activity tests with approximately 1,055 compounds amongextracts and fractions from different plants (569), vegetable oils (11) and synthetic orsemisynthetic substances (389). Currently, studies have shown that benzofuroxanderivatives were more cytotoxic than benznidazole for epimastigotes and amastigotes of T.cruzi. They are also not mutagenic in mice and can be produced in large quantities, whichencourages the need for further the understanding of their mechanism of action. Inaddition, polyene interactions with lipid membranes have been extensively studiedemploying small unilamellar vesicles (SUVs) and / or large (LUVs) using differentfluorescent techniques. The international team of Dr. Gregor Gomiscek from University ofLjubljana has been studying the interaction mechanisms by examining the individualbehavior of giant vesicles (GUVs). Interesting effects induced by different activity levelsof nystatin on lipid membrane were observed; these studies are carried out with phasecontrast microscopy and micromanipulation system. The purpose of this collaborativestudy is to evaluate the behavior of GUVs prepared with ergosterol or cholesterol after thetreatment with benzofuroxan derivatives. These results will bring interesting additionalinformation for a better understanding of the mechanism of action of these compoundsagainst trypanosomes membranes (containing ergosterol in its composition) compared tothose of the mammalian host (containing cholesterol in its composition).

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