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Specialized metabolites from Mikania nummularia DC. - structural characterization, evaluation of antiparasitic potential in vitro and in vivo, and determination of pharmacokinetic parameters

Grant number: 23/14422-6
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2024
Effective date (End): February 28, 2027
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:João Henrique Ghilardi Lago
Grantee:Marina de Monroe Gonçalves
Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Chagas disease and schistosomiasis, caused by the protozoa Trypasonoma cruzi and Schistosoma mansoni, respectively, are serious illnesses that have a high mortality and morbidity rate. Despite this, current treatments for these diseases face challenges, such as parasite resistance, low efficacy and adverse side effects. Therefore, in view of the historical importance that natural products play in the discovery of new drugs, the main objective of this project is to carry out a molecular dereplication study of extracts from Mikania nummularia DC., a species hitherto unexplored from a phytochemical point of view, which showed in vitro activity against T. cruzi and S. mansoni. After analyzing the chemical profile, the extracts that demonstrate activity against both parasites will be subjected to various chromatographic processes with the purpose of isolating special active metabolites. Sequentially, the isolated compounds will be characterized by different spectroscopic and spectrometric techniques. The in vitro antiparasitic potential of the isolated compounds will be evaluated in relation to extracellular and intracellular forms of T. cruzi and also in relation to adult S. mansoni worms. Additionally, the phenotypic mechanisms of action against the trypomastigote forms of T. cruzi will also be determined and the possible change in the morphology of the S. mansoni parasite will also be analyzed. In addition to these investigations, this study aims to study the permeability of bioactive compounds in vitro in artificial membranes PAMPA-TGI and PAMPA-BBB with a view to carrying out ex vivo tests in addition to allowing the selection of compounds with desirable pharmacokinetic characteristics for in vivo tests. . Therefore, the aim of this project is to contribute to the search for new bioactive prototypes for Chagas disease and schistosomiasis.

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