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Preclinical studies with epiisopiloturine and epiisopilosine and their effect against other helminths

Grant number: 16/18023-5
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): February 27, 2017
Effective date (End): November 26, 2017
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Yvonne Primerano Mascarenhas
Grantee:Ana Carolina Mafud
Supervisor: Jennifer Keiser
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Research place: Swiss Tropical and Public Health Institute (Swiss TPH), Switzerland  
Associated to the scholarship:14/02282-6 - Structure-activity relationship studies about of Pilocarpus microphyllus (Rutaceae) alkaloid derivatives against Schistosoma mansoni, BP.PD


Epiisopiloturine is an imidazole alkaloid extracted from Pilocarpus microphyllus Stapf ex Wardleworth, a Brazilian native plant, whose in vivo activity against Schistosoma mansoni led to parasite burden, to reduction in hepatosplenomegaly, the egg burden in faeces, and fell granuloma diameter. Epiisopilosine, another secondary metabolite from jaborandi, was tested in vitro (just accepted to publish) and at concentration of 3.125 ¼g/mL caused death of all adult worms after 96 hours incubation, besides prevent the mating and oviposition, reducing motor activity and altering the tegument of these worms. Previous biological assays showed the low toxicity of these alkaloids physicochemical and pharmacokinetic parameters point the anthelmintic activity. Once our main goal is get the knowledge of structure-activity relationship, preclinical studies will be conducted for the first time to check for structural changes generated by host metabolism. To verify the biological activity, they will be tested against a range of helminthiasis. (AU)

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Scientific publications (6)
(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)
ARARUNA, FELIPE BASTOS; DE OLIVEIRA, TAIANE MARIA; QUELEMES, PATRICK VERAS; DE ARAUJO NOBRE, ALYNE RODRIGUES; PLACIDO, ALEXANDRA; VASCONCELOS, ANDREANNE GOMES; MONTEIRO DE PAULA, REGINA CELIA; MAFUD, ANA CAROLINA; DE ALMEIDA, MIGUEL PEIXOTO; DELERUE-MATOS, CRISTINA; et al. Antibacterial application of natural and carboxymethylated cashew gum-based silver nanoparticles produced by microwave-assisted synthesis. Carbohydrate Polymers, v. 241, . (14/02282-6, 16/18023-5)
BARBOSA, EDER ALVES; OLIVEIRA, ANA; PLACIDO, ALEXANDRA; SOCODATO, RENATO; PORTUGAL, CAMILA C.; MAFUD, ANA CAROLINA; OMBREDANE, ALICIA S.; MOREIRA, DANIEL C.; VALE, NUNO; BESSA, LUCINDA J.; et al. Structure and function of a novel antioxidant peptide from the skin of tropical frogs. Free Radical Biology and Medicine, v. 115, p. 68-79, . (16/18023-5, 14/02282-6)
ARCANJO, DANIEL D. R.; VASCONCELOS, ANDREANNE G.; NASCIMENTO, LUCAS A.; MAFUD, ANA CAROLINA; PLACIDO, ALEXANDRA; ALVES, MICHEL M. M.; DELERUE-MATOS, CRISTINA; BEMQUERER, MARCELO P.; VALE, NUNO; GOMES, PAULA; et al. Structure-function studies of BPP-BrachyNH(2) and synthetic analogues thereof with Angiotensin I-Converting Enzyme. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 139, p. 401-411, . (16/18023-5)
DE OLIVEIRA, GUILHERME A. L.; DA SILVA OLIVEIRA, GEORGE L.; NICOLAU, LUCAS A. D.; MAFUD, ANA C.; BATISTA, LARISSA F.; MASCARENHAS, YVONNE P.; DE SOUZA, LUAN K. M.; DAVID, JORGE M.; PINTO, LARISSA S.; ALVES, CLAYTON Q.; et al. Bergenin from Peltophorum dubium: Isolation, Characterization, and Anti-oxidant Activities in Non-Biological Systems and Erythrocytes. Medicinal Chemistry, v. 13, n. 6, p. 592-603, . (14/02282-6, 16/18023-5)
GUIMARAES, MARIA A.; DE OLIVEIRA, ROSIMEIRE N.; DE ALMEIDA, REBECA L.; MAFUD, ANA C.; SARKIS, V, ANA L.; GANASSIN, RAYANE; DA SILVA, MARCOS P.; ROQUINI, DANIEL B.; VERAS, LEIZ M.; SAWADA, TANIA C. H.; et al. Epiisopilosine alkaloid has activity against Schistosoma mansoni in mice without acute toxicity. PLoS One, v. 13, n. 5, . (16/22488-3, 16/18023-5)
DE LIMA, LUIZA IANNY; PY-DANIEL, KAREN RAPP; GUIMAR, MARIA ADELAIDE; MUEHLMANN, LUIS ALEXANDRE; MAFUD, ANA CAROLINA; MASCARENHAS, YVONNE PRIMERANO; DE MORAES, JOSUE; ROBERTO DE SOUZA DE ALMEIDA LEITE, JOSE; JIANG, CHENG-SHI; AZEVEDO, RICARDO BENTES; et al. Self-nanoemulsifying drug-delivery systems improve oral absorption and antischistosomal activity of epiisopiloturine. Nanomedicine, v. 13, n. 7, p. 689-702, . (16/22488-3, 14/02282-6, 16/18023-5)

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