Exploring turmeric curcuminoids to treat schistosomiasis: an evaluation of their pre-clinical potential

• Grant number: 18/50011-2
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2018
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Agreement: University of California San Diego
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Lizandra Guidi Magalhães
• Grantee: Lizandra Guidi Magalhães
• Principal researcher abroad: Conor Robert Caffrey
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil
• Associated research grant: 16/24456-1 - Monoketo enone curcuminoids the treatment of schistosomiasis: an pre-clinical evaluation of schistosomicidal activity, AP.R

Abstract

The project emerged from a discussion between L. Caldas and C. Caffrey during the visit of Profa. Caldas in August 2016 to the Center for Discovery and Innovation in Parasitic Diseases (www.cdipd.org) at the University of California San Diego where Prof. Caffrey is a senior center director. During this visit, both PIs agreed to collaborate on the identification of new compounds against schistosomiasis. Accordingly, the central objective of this proposal is to explore curcuminoid compounds to identify molecular prototypes for the future application as novels drugs to treat schsitosomiasis. The activities will be focused on synthesis of curcuminoids, and their in vitro and in vivo evaluation against two different strains of the S. mansoni parasite (Puerto Rican (maintained by Caffrey) and Luis Evangelista (maintained by Caldas). Class-specific effects and structure-activity relationships will also be addressed. Further, proteomic analysis and cytotoxicity will be evaluated in in vitro for those active anti-schistosomal compounds. Based on their in vitro performance, active compounds will be assessed for toxicity in vivo, as well as for their therapeutic potential in the experimental mouse model of schistosome infection. (AU)

Scientific publications

(5)

(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)

A. DE L. PAULA, LUCAS; SANTOS, MARIO F. C.; PAGOTTI, MARIANA C.; FALEIROS, RENATA; RAMOS, HENRIQUE P.; VENEZIANI, RODRIGO C. S.; BASTOS, JAIRO K.; CAFFREY, CONOR R.; AMBROSIO, SERGIO R.; MAGALHAES, LIZANDRA G.. Uncovering Biological Application of Brazilian Green Propolis: A Phenotypic Screening againstSchistosoma mansoni. CHEMISTRY & BIODIVERSITY, v. 17, n. 9, AUG 2020. (17/04138-8, 18/50011-2)

DE L. PAULA, LUCAS A.; CANDIDO, ANA C. B. B.; SANTOS, MARIO F. C.; CAFFREY, CONOR R.; BASTOS, JAIRO K.; AMBROSIO, SERGIO R.; MAGALHAES, LIZANDRA G.. Antiparasitic Properties of Propolis Extracts and Their Compounds. CHEMISTRY & BIODIVERSITY, v. 18, n. 9, JUL 2021. (17/04138-8, 18/50011-2)

PAULA, LUCAS A. DE L.; SANTOS, MARIO F. C.; PAGOTTI, MARIANA C.; VENEZIANI, RODRIGO C. S.; BASTOS, JAIRO K.; CAFFREY, CONOR R.; AMBROSIO, SERGIO R.; MAGALHAES, LIZANDRA G.. razilian green propolis reduces worm burden and hepatic granuloma formation in a Schistosoma mansoni experimental murine mode. Parasitology Research, v. 121, n. 2, p. 775-780, FEB 2022. (18/50011-2, 17/04138-8, 18/25010-2, 18/05080-6)

BADOCO, FERNANDA R.; PAULA, LUCAS A. L.; ORENHA, RENATO P.; MENDES, TIAGO M. F.; SQUARISI, IARA S.; EL-SAKKARY, NELLY; LOIOLA, MESSIAS C.; KATZ, NAFTALE; TAVARES, DENISE C.; SAIRRE, MIRELA I.; et al. EF24, a schistosomicidal curcumin analog: Insights from its synthesis and phenotypic, biochemical and cytotoxic activities. Chemico-Biological Interactions, v. 368, p. 11-pg., 2022-10-13. (17/24856-2, 18/50011-2, 15/01394-8, 14/02018-7, 16/18045-9, 16/24456-1)

FRANCISCO, KAROL R.; MONTI, LUDOVICA; YANG, WENQIAN; PARK, HAYOUNG; LIU, LAWRENCE J.; WATKINS, KAITLYN; AMARASINGHE, DILINI K.; NALLI, MARIANNA; POLAQUINI, CARLOS ROBERTO; REGASINI, LUIS O.; et al. Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei. Bioorganic & Medicinal Chemistry Letters, v. 81, p. 9-pg., 2023-01-25. (16/24456-1, 18/50011-2)