Metabolites from fruit peels of Porcelia macrocarpa (Warm.) R. E. Fries (Annonaceae): molecular dereplication, evaluation of antiparasitic potential and study of the phenotypic and metabolomic modes of action

• Grant number: 20/01221-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2020
• End date: October 16, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: João Henrique Ghilardi Lago
• Grantee: Fernanda Thevenard dos Santos
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Plant species, as well as other natural products, have been used as therapeutics for treatment of several diseases since ancient times. There is great chemodiversity in plants, which make them important sources for new drug development studies, including for neglected diseases such as Chagas Disease. Therefore, this project aims to conduct a molecular dereplication study of Porcelia macrocarpa (Warm.) R. E. Fries fruit peel extract, a plant tissue not yet explored. For this, the extract will be evaluated by NMR and HPLC/MS followed by bioassay-guided fractionation for isolation of active compounds, which will be characterized by spectrometric/spectroscopic techniques. Sequentially, the activity of the metabolites with antiparasitic potential will be evaluated against extra and intracellular forms of Trypanosoma cruzi and in-depth studies regarding possible modes of action of these compounds will be performed. Additionally, evaluation of these mechanisms will be complemented with metabolomic studies of the parasites when treated with the active compounds. Finally, the pharmacokinetic properties of the isolated substances will be analyzed (ADME/Tox and PAINS) in order rationalize possible structural changes to better the observed biological potential. Thus, the results obtained will contribute to the number of prototypes available for drug development, especially regarding anti-T.cruzi activity, as well as a deeper understanding of the active compounds' mode of action against the parasites. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTANA, FERNANDA PAULA R.; THEVENARD, FERNANDA; GOMES, KAIO S.; TAGUCHI, LAURA; CAMARA, NIELS OLSEN S.; STILHANO, ROBERTA S.; URESHINO, RODRIGO P.; PRADO, CARLA MAXIMO; LAGO, JOAO HENRIQUE GHILARDI. New perspectives on natural flavonoids on COVID-19-induced lung injuries. Phytotherapy Research, v. 35, n. 9, p. 4988-5006, SEP 2021. (20/01221-4, 18/07885-1, 18/06088-0)

THEVENARD, FERNANDA; BRITO, IVANILDO A.; COSTA-SILVA, THAIS A.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.. Enyne acetogenins from Porcelia macrocarpa displayed anti-Trypanosoma cruzi activity and cause a reduction in the intracellular calcium level. SCIENTIFIC REPORTS, v. 13, n. 1, p. 10-pg., 2023-06-24. (21/02789-7, 21/04464-8, 20/01221-4)