Structure-activity relationship studies about of Pilocarpus microphyllus (Rutaceae) alkaloid derivatives against Schistosoma mansoni

• Grant number: 14/02282-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2014
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Yvonne Primerano Mascarenhas
• Grantee: Ana Carolina Mafud
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID
• Associated scholarship(s): 16/18023-5 - Preclinical studies with epiisopiloturine and epiisopilosine and their effect against other helminths, BE.EP.PD

Abstract

Pilocarpine is an alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native plant from Brazil, known as jaborandi, which presents muscarinic agonist activity, and it is used as a miotic agent in the treatment of glaucoma. The alkaloid imidazole Epiisopiloturina (EPI) comprises 70% of purifying residue, with activity against Schistosma mansoni, and other compounds of the same family as the macaubina and pilosina. Schistosomiasis, caused by parasites of the genus Schistosoma, still imposes a considerable public health problem and its control depends almost exclusively praziquantel (PZQ). In this work, we intend to elucidate the crystal structures of alkaloids obtained through purification of pilocarpine and its structural and isomers, and their metallated complexes besides analyzing the similarity between them and increase their chemistry class for virtual screening of ligands. Finally, we intend to look for a biological target through the topological analysis of drugs with known targets, using a three-dimensional crystallographic structure and description in order to define a pharmacophore. (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)

MAFUD, ANA CAROLINA; REINHEIMER, ERIC W.; DALMATTI ALVES LIMA, FILIPE CAMARGO; BATISTA, LARISSA FERNANDES; DE PAULA, KARINA; COSTA VERAS, LEIZ MARIA; DE SOUZA DE ALMEIDA LEITE, JOSE ROBERTO; VENANCIO, TIAGO; MASCARENHAS, YVONNE PRIMERANO. Supramolecular assembly in the epiisopiloturine hydrochloride salt. Journal of Molecular Structure, v. 1136, p. 204-213, MAY 15 2017. (14/02282-6, 13/07600-3)

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, AUG 1 2020. (14/02282-6, 16/18023-5)

MAFUD, ANA C.; FERREIRA, LEONARDO G.; MASCARENHAS, YVONNE P.; ANDRICOPULO, ADRIANO D.; DE MORAES, JOSUE. Discovery of Novel Antischistosomal Agents by Molecular Modeling Approaches. Trends in Parasitology, v. 32, n. 11, p. 874-886, NOV 2016. (14/02282-6, 13/25658-9, 13/07600-3)

ADRIANY, AMORIM; JESSICA, SOUZA; ANA, OLIVEIRA; RAIMUNDA, SANTOS; ANDREANNE, VASCONCELOS; LUAN, SOUZA; THIAGO, ARAUJO; WANESSA, CABRAL; MARIA, SILVA; ANA, MAFUD; et al. Anti-inflammatory and antioxidant activity improvement of lycopene from guava on nanoemulsifying system. JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY, v. 42, n. 5, p. 11-pg., 2020-02-29. (14/02282-6)

CAMPELO, YURI; OMBREDANE, ALICIA; VASCONCELOS, ANDREANNE G.; ALBUQUERQUE, LUCAS; MOREIRA, DANIEL C.; PLACIDO, ALEXANDRA; ROCHA, JEFFERSON; FOKOUE, HAROLD HILARION; YAMAGUCHI, LYDIA; MAFUD, ANA; et al. Structure-Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 6, p. 17-pg., 2018-06-01. (16/22488-3, 14/50316-7, 14/02282-6)

CAMPELO, YURI; OMBREDANE, ALICIA; VASCONCELOS, ANDREANNE G.; ALBUQUERQUE, LUCAS; MOREIRA, DANIEL C.; PLACIDO, ALEXANDRA; ROCHA, JEFFERSON; FOKOUE, HAROLD HILARION; YAMAGUCHI, LYDIA; MAFUD, ANA; et al. Structure-Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 6, JUN 2018. (16/22488-3, 14/02282-6, 14/50316-7)

ADRIANY, AMORIM; JESSICA, SOUZA; ANA, OLIVEIRA; RAIMUNDA, SANTOS; ANDREANNE, VASCONCELOS; LUAN, SOUZA; THIAGO, ARAUJO; WANESSA, CABRAL; MARIA, SILVA; ANA, MAFUD; et al. nti-inflammatory and antioxidant activity improvement of lycopene from guava on nanoemulsifying syste. JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY, v. 42, n. 5, FEB 2020. (14/02282-6)

AMORIM, ADRIANY G. N.; SOUZA, JESSICA M. T.; SANTOS, RAIMUNDA C.; GULLON, BEATRIZ; OLIVEIRA, ANA; SANTOS, LUIZ F. A.; VIRGINO, ADAMOR L. E.; MAFUD, ANA C.; PETRILLI, HELENA M.; MASCARENHAS, YVONNE P.; et al. HPLC-DAD, ESI-MS/MS, and NMR of Lycopene Isolated From P-guajava L. and Its Biotechnological Applications. EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, v. 120, n. 3, MAR 2018. (14/02282-6)

PLACIDO, ALEXANDRA; DE OLIVEIRA FARIAS, EMANUEL AIRTON; MARANI, MARIELA M.; VASCONCELOS, ANDREANNE G.; MAFUD, ANA C.; MASCARENHAS, YVONNE P.; EIRAS, CARLA; LEITE, JOSE R. S. A.; DELERUE-MATOS, CRISTINA. Layer-by-layer films containing peptides of the Cry1Ab16 toxin from Bacillus thuringiensis for potential biotechnological applications. Materials Science & Engineering C-Materials for Biological Applications, v. 61, p. 832-841, APR 1 2016. (14/02282-6)

CARDOSO, VINICIUS SAURA; FILGUEIRAS, MARCELO DE CARVALHO; DUTRA, YAGO MEDEIROS; GOMES TELES, RAMON HANDERSON; DE ARAUJO, ALYNE RODRIGUES; PRIMO, FERNANDO LUCAS; MAFUD, ANA CAROLINA; BATISTA, LARISSA FERNANDES; MASCARENHAS, YVONNE PRIMERANO; MARTINEZ PAINO, IEDA MARIA; et al. Collagen-based silver nanoparticles: Study on cell viability, skin permeation, and swelling inhibition. Materials Science & Engineering C-Materials for Biological Applications, v. 74, p. 382-388, MAY 1 2017. (15/10267-0, 14/02282-6)

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, 2017. (14/02282-6, 16/18023-5)

ARCANJO, DANIEL D. R.; MAFUD, ANA CAROLINA; VASCONCELOS, ANDREANNE G.; DA SILVA-FILHO, JOSE COURAS; AMARAL, MAURICIO P. M.; BRITO, LUCAS M.; BEMQUERER, MARCELO P.; KUCKELHAUS, SELMA A. S.; PLACIDO, ALEXANDRA; DELERUE-MATOS, CRISTINA; et al. In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH(2), A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium. INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS, v. 23, n. 3, p. 323-331, SEP 2017. (14/02282-6)

MAFUD, ANA C.; SILVA, MARCOS P. N.; NUNES, GEANDRA B. L.; DE OLIVEIRA, MILENE A. R.; BATISTA, LARISSA F.; RUBIO, THIAGO I.; MENGARDA, ANA C.; LAGO, ELOI M.; XAVIER, ROGERIO P.; GUTIERREZ, STANLEY J. C.; et al. Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives. TOXICOLOGY IN VITRO, v. 50, p. 1-10, AUG 2018. (16/22488-3, 14/02282-6)

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, APR 2018. (16/22488-3, 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, FEB 1 2018. (16/18023-5, 14/02282-6)

GUIMARAES, MARIA A.; DE OLIVEIRA, ROSIMEIRE N.; VERAS, LEIZ M. C.; LIMA, DAVID F.; CAMPELO, YURI D. M.; CAMPOS, STEFANO AUGUSTO; KUCKELHAUS, SELMA A. S.; PINTO, PEDRO L. S.; EATON, PETER; MAFUD, ANA C.; et al. Anthelmintic Activity In Vivo of Epiisopiloturine against Juvenile and Adult Worms of Schistosoma mansoni. PLoS Neglected Tropical Diseases, v. 9, n. 3, MAR 2015. (14/02282-6)

PORTES, MARCELO CECCONI; DE MORAES, JOSUE; COSTA VERAS, LEIZ MARIA; LEITE, JOSE ROBERTO; MAFUD, ANA CAROLINA; MASCARENHAS, YVONNE PRIMERANO; VIRGINO LUZ, ADAMOR ELEIEL; DALMATTI ALVES DE LIMA, FILIPE CAMARGO; DO NASCIMENTO, RAFAEL RODRIGUES; PETRILLI, HELENA MARIA; et al. Structural and spectroscopic characterization of epiisopiloturine-metal complexes, and anthelmintic activity vs. S-mansoni. Journal of Coordination Chemistry, v. 69, n. 10, p. 1663-1683, 2016. (11/50318-1, 14/02282-6, 12/02326-8, 13/07937-8)

DE AGUIAR, INARA; DOS SANTOS, EDJANE ROCHA; MAFUD, ANA CAROLINA; ANNIES, VINICIUS; NAVARRO-SILVA, MARIO ANTONIO; DOS SANTOS MALTA, VALERIA RODRIGUES; DO PRADO GAMBARDELLA, MARIA TERESA; MARQUES, FRANCISCO DE ASSIS; CARLOS, ROSE MARIA. Synthesis and characterization of Mn(I) complexes and their larvicidal activity against Aedes aegypti, vector of dengue fever. Inorganic Chemistry Communications, v. 84, p. 49-55, OCT 2017. (09/08218-0, 14/02282-6)

MAFUD, ANA C.; SILVA, MARCOS P. N.; MONTEIRO, DANIELA C.; OLIVEIRA, MARIA F.; RESENDE, JOAO G.; COELHO, MAYARA L.; DE SOUSA, DAMIAO P.; MENDONCA, RONALDO Z.; PINTO, PEDRO L. S.; FREITAS, RIVELILSON M.; et al. Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite. Chemico-Biological Interactions, v. 244, p. 129-139, JAN 25 2016. (14/02282-6)

DOBRACHINSKI, LEANDRO; FERREIRA, LEONARDO L. G.; CIRINO, MARIA E.; ANDRADE-DE-SIQUEIRA, ALLAN, I; MAFUD, ANA C.; MASCARENHAS, YVONNE P.; ANDRICOPULO, ADRIANO D.; DE MORAES, JOSUE. The 3D pharmacophore modeling to explore new antischistosomal agents among US FDA approved drugs. Future Medicinal Chemistry, v. 16, n. 17, p. 9-pg., 2024-07-25. (16/18023-5, 14/02282-6, 13/25658-9, 13/07600-3, 16/22488-3)

PLACIDO, ALEXANDRA; DE OLIVEIRA FARIAS, EMANUEL AIRTON; MARANI, MARIELA M.; VASCONCELOS, ANDREANNE G.; MAFUD, ANA C.; MASCARENHAS, YVONNE P.; EIRAS, CARLA; LEITE, JOSE R. S. A.; DELERUE-MATOS, CRISTINA. Layer-by-layer films containing peptides of the Cry1Ab16 toxin from Bacillusthuringiensis for potential biotechnological applications. Materials Science & Engineering C-Materials for Biological Applications, v. 61, p. 10-pg., 2016-04-01. (14/02282-6)