Searching for bioactive metabolites from Brazilian biodiversity as drug candidates for diseases caused by parasitic worms

• Grant number: 23/08418-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Josué de Moraes
• Grantee: Josué de Moraes
• Host Institution: Universidade Universus Veritas Guarulhos (Univeritas UNG). Guarulhos , SP, Brazil
• Associated researchers: Ademar Alves da Silva Filho ; Adriano Defini Andricopulo ; Carolina Horta Andrade ; Damião Pergentino de Sousa ; João Henrique Ghilardi Lago ; Maria Cecília Barbosa da Silveira Salvadori

Abstract

The neglected diseases caused by helminths affect more than one billion people, mostly children, and have a significant impact on health, education, productivity, and socioeconomic development. Chemotherapy remains the primary method of controlling these diseases, but the number and effectiveness of available drugs are limited. Recognizing this challenge, the World Health Organization (WHO), in its new roadmap with global goals and milestones for the control of neglected diseases by 2030, emphasizes the importance of searching for new anthelmintic agents. In this context, considering that Brazilian biodiversity is a promising source of molecules with pharmacological activity, our research group, in collaboration with several researchers, particularly those involved in the BIOTA-FAPESP Program, has been making efforts to search for natural bioactive substances with anthelmintic action, especially those derived from Brazilian plant species. The present project aims to continue prospecting studies of bioactive molecules, focusing on the search for prototypes with antiparasitic action against Schistosoma mansoni, Toxocara canis, Angiostrongylus cantonensis, and Caenorhabditis elegans. To achieve this, we will conduct tests on samples from the natural compound bank of various national programs, as well as conduct biomonitoring studies using plant extracts/fractions. Isolated compounds will be chemically characterized and tested for their anthelmintic effects. Once active substances are identified in vitro, in vivo assays will be conducted using the murine schistosomiasis model. Active molecules may also undergo molecular modifications guided by in silico analysis of ADME/Tox properties to optimize biological activities and/or reduce toxicity. The objective of this proposal is to identify new anthelmintic compounds of natural origin, thereby contributing to expanding the limited therapeutic options available for neglected diseases. Additionally, the proposal aims to contribute to the training of human resources in various areas of knowledge. (AU)

Scientific publications

(8)

(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)

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)

FERREIRA, EVERTON ALLAN; CAMPOS, IGOR MOREIRA; CAJAS, RAYSSA A.; COSTA, DANILO DE SOUZA; CARVALHO, LARA SOARES ALEIXO DE; FRANKLIN, PAULA FERNANDES DA COSTA; DE NIGRO, NATHALIA DE PAULA D.; PINTO, PRISCILA DE FARIA; CAPRILES, PRISCILA V. . S. Z.; DE MORAES, JOSUE; et al. In vivo efficacy of uvangoletin from Piper aduncum (Piperaceae) against Schistosoma mansoni and in silico studies targeting SmNTPDases. Experimental Parasitology, v. 269, p. 9-pg., 2025-01-15. (23/08418-6)

COGO, RAMON M.; PAVANI, THAIS F. A.; MENGARDA, ANA C. A.; CAJAS, RAYSSA A.; TEIXEIRA, THAINA R.; FUKUI-SILVA, LUCAS; SUN, YUJIE ULI; LIU, LAWRENCE J.; AMARASINGHE, DILINI K.; YOON, MICHAEL C.; et al. Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity. ACS OMEGA, v. 9, n. 23, p. 14-pg., 2024-05-30. (16/22488-3, 23/08418-6, 19/26686-2)

OLIVEIRA, MARIA D. A.; ANDRADE, TERESINHA DE JESUS A. DOS S.; JOAQUIM JR, S. C.; LIMA, NERILSON MARQUES; MACHADO, HUGO G.; TABUDRAVU, JIOJI N.; PINTO, FRANCISCO DAS CHAGAS L.; FUKUI-SILVA, LUCAS; AMARO, MONIQUE C.; DE MORAES, JOSUE; et al. Anthelmintic Potential of Conjugated Long-Chain Fatty Acids Isolated from the Bioluminescent Mushroom Neonothopanus gardneri. Journal of Natural Products, v. N/A, p. 7-pg., 2025-01-04. (23/08418-6)

DANTAS, ADRIANE M. C.; TEIXEIRA, FERNANDA S.; OBLITAS, RAISSA L.; ARAUJO, WAGNER W. R.; AMARO, MONIQUE C.; CAJAS, RAYSSA A.; DE MORAES, JOSUE; SALVADORI, MARIA C.. Atomic force microscopy reveals morphological and mechanical properties of schistosoma mansoni tegument. SCIENTIFIC REPORTS, v. 14, n. 1, p. 12-pg., 2024-10-04. (23/08418-6)

COSTA, DANILO DE SOUZA; CAJAS, RAYSSA A.; LEAL, CARLA MONTEIRO; DE CARVALHO, LARA S. ALEIXO; SOUZA, LARA CRUZ DE; FUKUI-SILVA, LUCAS; DE MORAES, JOSUE; FILHO, ADEMAR A. DA SILVA. Efficacy of spilanthol and Acmella oleracea (L.) R. K. Jansen (Asteraceae) extract against Schistosoma mansoni infection. Journal of Ethnopharmacology, v. 338, p. 10-pg., 2025-02-10. (23/08418-6, 20/01441-4)

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)

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)