Searching for specialized metabolites from Brazilian floristic biodiversity as drug candidates for neglected tropical diseases

• Grant number: 23/12447-1
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: João Henrique Ghilardi Lago
• Grantee: João Henrique Ghilardi Lago
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated researchers: André Gustavo Tempone Cardoso ; Josué de Moraes ; Luciano Caseli ; Luiz Felipe Domingues Passero ; Patricia Sartorelli
• Associated research grant(s): 24/19277-7 - Silver nanoparticles obtained from natural products for the treatment of infections caused by multiresistant bacteria, AP.R SPRINT

Abstract

The neglected diseases caused by parasites affect more than one billion people and represent a negative impact on health, education, productivity and socioeconomic development. Chemotherapy remains the main method of controlling these diseases, but the available drugs are limited in number and effectiveness. Aware of this problem, the World Health Organization (WHO), in its new roadmap with global goals and milestones for the control of neglected diseases by the year 2030, emphasizes the importance of the search for new antiparasitic agents. In this context, considering that Brazilian biodiversity is a promising source of molecules with pharmacological activity, our research group, together with several researchers, has been making efforts in the search for natural bioactive substances with antiparasitic action, mainly those originating from Brazilian plant species. Thus, in this project, continuity will be given to prospecting studies of bioactive molecules, particularly with regard to studies of prospecting bioactive molecules, especially with antiparasitic action (antileishmania, antitrypanosomal and/or anthelmintic), derived from plant species belonging to mainly to Annonaceae, Asteraceae, Lauraceae and Piperaceae that occur in areas of the Atlantic Forest and Cerrado in the State of São Paulo. For this purpose, the species will be collected, and their extracts prepared, and those with proven antiparasitic action will be subjected to molecular dereplication processes through analysis via HPLC/MS aided by the open platform Global Natural Products Social Molecular Networking (GNPS). Once new bioactive chemical entities are recognized, they will be isolated and structurally characterized. After identifying the active substances, they may be subjected to molecular modifications guided by analysis of ADME/Tox in silico properties aimed at optimizing biological activities and/or reducing toxicity. Additionally, this proposal intends to carry out specific tests to define the phenotypic/molecular mode of action of substances with proven activity in relation to the parasite, in particular the evaluation of the membrane pore and ultrastructural studies. Finally, the selected compounds (natural or semi-synthetic) that have high potential in vitro, reduced toxicity and that meet the criteria recommended by the analyzes via ADME/Tox in silico and, in particular, if they prove to be stable through assays using murine hepatocytes (model experimental) will be submitted to experimental studies (in vivo). Thus, this project intends to add new compounds with proven pharmacological activity to the restricted therapeutic arsenal of these neglected diseases, providing tools for the development of new drugs of plant origin. (AU)

Scientific publications

(21)

(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)

TRISTAO, DANIELA C.; BARBOSA, HENRIQUE; LEVATTI, ERICA V. DE CASTRO; ANDRADE, BEATRIZ A.; ROMANELLI, MAIARA M.; ANTAR, GUILHERME M.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.. Selective Activity Against Amastigote Forms of Trypanosoma cruzi and Leishmania infantum of Diastereomeric Dicentrine N-oxides. CHEMISTRY & BIODIVERSITY, v. 21, n. 9, p. 6-pg., 2024-08-11. (21/04464-8, 23/12447-1)

UMEHARA, ERIC; CAJAS, RAYSSA A.; CONCEICAO, GABRIEL B.; ANTAR, GUILHERME M.; ANDRICOPULO, ADRIANO D.; DE MORAES, JOSUE; LAGO, JOAO HENRIQUE G.. In Vitro and In Vivo Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from Drimys brasiliensis Branches. Molecules, v. 30, n. 2, p. 11-pg., 2025-01-01. (23/08418-6, 23/12447-1, 13/07600-3)

JESUS, JESSICA ADRIANA; ARAUJO FLORES, GABRIELA VENICIA; SOUZA, DALETE CHRISTINE DA SILVA; TRISTAO, DANIELA COSTA; SERRANO, DOLORES REMEDIOS; LALATSA, AIKATERINA; LAURENTI, MARCIA DALASTRA; LAGO, JOAO HENRIQUE GHILARDI; FERRAZ, HUMBERTO GOMES; DA SILVA, ROSANA PEREIRA; et al. Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis. MICROORGANISMS, v. 13, n. 2, p. 17-pg., 2025-02-01. (22/15834-3, 14/50315-0, 23/12447-1, 23/01641-1)

UMEHARA, ERIC; TEIXEIRA, THAINA R.; CAJAS, RAYSSA A.; AMARO, MONIQUE C.; DE MORAES, JOSUE; LAGO, JOAO HENRIQUE G.. EDBD-3,6-Epidioxy-1,10-Bisaboladiene-An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection. ANTIBIOTICS-BASEL, v. 13, n. 8, p. 10-pg., 2024-08-01. (23/08418-6, 23/12447-1)

REIS, ISABELLA MARY ALVES; DA SILVA, GIRLIANE REGINA; DE MATTOS OLIVEIRA, LARISSA; DOS SANTOS JR, MANOELITO COELHO; DA SILVA, TANIA MARIA SARMENTO; VIEIRA, IVO JOSE CURCINO; BRAZ-FILHO, RAIMUNDO; ROMANELLI, MAIARA MARIA; AMARAL, MAIARA; TEMPONE, ANDRE GUSTAVO; et al. In Vitro and In Silico Evaluation of the Leishmanicidal and Trypanocidal Activities of Lignan Methylpiperitol Isolated from Persea Fulva. CHEMISTRY & BIODIVERSITY, v. 21, n. 8, p. 7-pg., 2024-07-31. (23/12447-1)

OLIVEIRA, LARISSA V. F.; CAMILO, FERNANDA F.; SOARES, MARISI G.; CAJAS, RAYSSA A.; CIRINO, MARIA E.; DE MORAES, JOSUE; LAGO, JOAO HENRIQUE G.. In Situ Preparation of Dehydrodieugenol-Loaded Silver Nanoparticles and their Antischistosomal Activity. CHEMISTRY & BIODIVERSITY, v. 21, n. 3, p. 8-pg., 2024-02-21. (21/07971-8, 21/08987-5, 23/12447-1, 21/02789-7)

GOMES, KAIO S.; COELHO, JULIA A.; GOMES, RAFAEL N.; BOSQUETTI, LUCAS M.; LANGE, CAMILA N.; BATISTA, BRUNO L.; CERCHIARO, GISELLE; LAGO, JOAO HENRIQUE G.. Dehydrodieugenol isolated from Ocotea cymbarum induces cell death in human breast cancer cell lines by dysregulation of intracellular copper concentration. Chemico-Biological Interactions, v. 396, p. 6-pg., 2024-05-08. (23/12447-1)

DA SILVA, GUSTAVO H. O.; DOS SANTOS, KEVIN F.; BARCELLOS, ALINE F.; DE SOUSA, RAQUEL M. FERREIRA; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.; CASELI, LUCIANO. Exploring the selective incorporation of 15β-senecioyloxi-ent-kaurenoic acid methyl ester in Langmuir monolayers mimicking cell membranes. BIOORGANIC CHEMISTRY, v. 153, p. 12-pg., 2024-12-01. (18/22214-6, 23/12447-1, 22/03736-7)

ACCIOLY JR, MARCOS; RIBEIRO, FERNANDA S.; AMARAL, MAIARA; LEVATTI, ERICA V. C.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.; UEMI, MIRIAM. Antitrypanosomal activity of new alkoxyhydroperoxides formed by cycloaddition of ozone into allyl moiety of eugenol. Tetrahedron, v. 159, p. 6-pg., 2024-05-08. (23/12447-1, 14/14801-8)

VOLPE-FIX, ANDRESSA ROEHRIG; SALES, FELIPE DA SILVA; CAPERUTO, LUCIANA CHAGAS; LAGO, JOAO HENRIQUE GHILARDI; MACHADO-JR, JOEL. Essential Oil Extracted from Lippia sidoides Cham. (Verbenaceae) Induces Cell Cycle Arrest, Apoptosis, and Antimigratory Effects in Melanoma Cells. CHEMISTRY & BIODIVERSITY, v. N/A, p. 10-pg., 2024-10-31. (23/12447-1)

FERREIRA, BRUNO ANTONIO; MOURA, FRANCYELLE BORGES ROSA DE; CASSIMIRO, ISABELLA SILVA; LONDERO, VINICIUS SILVA; GONSALVES, MARINA DE MONROE; LAGO, JOAO HENRIQUE GHILARDI; ARAUJO, FERNANDA DE ASSIS. Costic acid, a sesquiterpene from Nectandra barbellata (Lauraceae), attenuates sponge implant-induced inflammation, angiogenesis and collagen deposition in vivo. Fitoterapia, v. 175, p. 9-pg., 2024-04-04. (23/12447-1, 21/02789-7)

BRITO, IVANILDO A.; LEVATTI, ERICA V. CASTRO; REGASINI, LUIS O.; FERREIRA, EDGARD A.; LOPES, FLAVIA B.; FERNANDES, JOAO PAULO S.; BATISTA JR, JOAO M.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.. Homologous acetylenic acetogenins from Porcelia macrocarpa RE (Fries) displayed potent activity against amastigotes from Trypanosoma cruzi. Phytochemistry, v. 231, p. 10-pg., 2024-12-17. (23/12447-1, 23/12475-5, 19/22319-5)

DE M. GONCALVES, MARINA; TOTINI, CARLOS H.; DE CASTRO, ERICA V.; ALBUQUERQUE, VANESSA; ANTAR, GUILHERME M.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.. Lignans Isolated from Piper truncatum Act as New Potent Antitrypanosomal Compounds. CHEMISTRY & BIODIVERSITY, v. 21, n. 5, p. 6-pg., 2024-04-12. (21/04464-8, 23/12447-1)

SILVA, MATHEUS L.; SALES, FELIPE S.; LEVATTI, ERICA V. C.; ANTAR, GUILHERME M.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.; JERZ, GEROLD. Evaluation of Anti-Trypanosoma cruzi Activity of Chemical Constituents from Baccharis sphenophylla Isolated Using High-Performance Countercurrent Chromatography. Molecules, v. 29, n. 1, p. 13-pg., 2024-01-01. (21/04464-8, 23/12447-1, 20/03637-3, 21/02789-7)

ROSA, MATHEUS E.; TRISTAO, DANIELA C.; BARBOSA, HENRIQUE; MENDES, VIVIANE M.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.; CASELI, LUCIANO. Exploring the antileishmanial activity of dicentrine from Ocotea puberula (Lauraceae) using biomembrane models. BIOORGANIC CHEMISTRY, v. 147, p. 7-pg., 2024-04-27. (18/22214-6, 23/12447-1, 21/15084-1)

GOMES, KAIO S.; COSTA-SILVA, THAIS A.; BORGES, WARLEY S.; ANDRADE, BEATRIZ A.; FERREIRA, DAYANA A.; TEMPONE, ANDRE G.; RYFFEL, DAVID; SARLAH, DAVID; LAGO, JOAO HENRIQUE G.. Antiparasitic Activity of Narciclasine and Evaluation of Its Effects on Plasma Membrane and Mitochondria of Trypanosoma cruzi. ACS OMEGA, v. 10, n. 3, p. 8-pg., 2025-01-14. (23/12447-1, 19/13906-4)

KATCHBORIAN-NETO, ALBERT; ALVES, MATHEUS F.; BUENO, PAULA C. P.; DE JESUS NICACIO, KAREN; FERREIRA, MILLER S.; OLIVEIRA, TIAGO B.; BARBOSA, HENRIQUE; MURGU, MICHAEL; DE PAULA LADVOCAT, ANA C. C.; DIAS, DANIELLE F.; et al. Integrative open workflow for confident annotation and molecular networking of metabolomics MS^E/DIA data. BRIEFINGS IN BIOINFORMATICS, v. 25, n. 2, p. 18-pg., 2024-01-22. (23/12447-1, 21/02789-7)

SOUZA, DALETE CHRISTINE S.; TOTINI, CARLOS H.; CAJAS, RAYSSA A.; TEIXEIRA, THAINA R.; OLIVEIRA, EMERSON A.; CIRINO, MARIA E.; SOUZA, MARIA C.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; DE MORAES, JOSUE; et al. In vivo antischistosomal efficacy of Porcelia ponderosa γ-lactones. Phytomedicine, v. 135, p. 9-pg., 2024-09-18. (23/08418-6, 23/12447-1)

SILVA, MATHEUS L.; BALDIM, JOAO L.; COSTA-SILVA, THAIS A.; AMARAL, MAIARA; ROMANELLI, MAIARA M.; LEVATTI, ERICA V. C.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.. Effect of the Alkyl Side Chain of Antitrypanosomal Cinnamate, p-Coumarate, and Ferulate n-Alkyl Esters Using Multivariate Analysis and Computer-Aided Drug Design. Journal of the Brazilian Chemical Society, v. 36, n. 8, p. 7-pg., 2025-01-01. (23/12447-1)

BALTAZAR, FABIO NAVARRO; AMARAL, MAIARA; ROMANELLI, MAIARA MARIA; LEVATTI, ERICA VALADARES DE CASTRO; RAMOS, FERNANDA FONSECA; LEAO, LUIZ LUIZ PAULO MELCHIOR OLIVEIRA; CHAGAS-PAULA, DANIELA APARECIDA; SOARES, MARISI GOMES; DIAS, DANIELLE FERREIRA FERREIRA; ARANHA, CECILIA M. S. Q.; et al. Toward New Therapeutics for Visceral Leishmaniasis: Efficacy and Mechanism of Action of Amides Inspired by Gibbilimbol B. ACS OMEGA, v. 9, n. 44, p. 11-pg., 2024-10-08. (21/04464-8, 23/12447-1, 20/03637-3, 18/25128-3)

PERES, NATHALIA; SILVA, MATHEUS L.; UENO, ANDERSON K.; ANTAR, GUILHERME M.; LEVATTI, ERICA V. C.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G.. Highly selective alkylcoumarates and diterpenoids isolated from leaves of Baccharis quitensis: a search for new hit compounds against Trypanosoma cruzi. NATURAL PRODUCT RESEARCH, v. N/A, p. 7-pg., 2024-03-25. (21/04464-8, 23/12447-1)