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Drug repositioning for neglected diseases: identification of novel anthelmintic agents

Grant number: 16/22488-3
Support Opportunities:Regular Research Grants
Duration: May 01, 2017 - April 30, 2019
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 ; Ana Carolina Mafud ; Damião Pergentino de Sousa ; José Roberto de Souza de Almeida Leite ; Marta Ferreira Bastos ; Yvonne Primerano Mascarenhas

Abstract

The diseases caused by helminth parasites occur mainly in the poorest social strata, without adequate housing, work, education, health services. Also known as "diseases of poverty", these diseases affect more than 1 billion people worldwide and are responsible for millions of deaths annually. Unfortunately, treatment options are insufficient, whose screenplay is exacerbated by disregard of the pharmaceutical industry in developing new drugs for low-income population. Considered a neglected disease, schistosomiasis is considered an important public health problem in more than 70 countries. It is estimated that there, worldwide, more than 200 million individuals infected and 800 million people are at risk. Currently, treatment of schistosomiasis is based on the use of only one drug, praziquantel, but extensive and inappropriate use culminated in the emergence of resistance. Additionally, praziquantel is the most widely drugs used for the treatment and control of parasites in domestic and farm animals. In this sense, the main activities are research and technological development for the control of schistosomiasis and other helminthiasis. The search for new therapies, drug repositioning has been a promising strategy with the use of drugs already available and approved for clinical use in other diseases. This project aims to study new therapies with the use of drugs (repositioning) using Schistosoma mansoni worm (BH strain) as experimental model. Using bioassays, we aim to obtain novel drugs with ex vivo and in vivo anthelmintic properties. Moreover, this project aims to contribute to the training of human resources. (AU)

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Scientific publications (36)
(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)
SILVA, MARCOS P.; DE OLIVEIRA, ROSIMEIRE N.; MENGARDA, ANA C.; ROQUINI, DANIEL B.; ALLEGRETTI, SILMARA M.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; DE SOUSA, DAMIAO P.; PINTO, PEDRO L. S.; DA SILVA FILHO, ADEMAR A.; et al. Antiparasitic activity of nerolidol in a mouse model of schistosomiasis. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 50, n. 3, p. 467-472, . (16/22488-3)
ROCHA, JEFFERSON A.; REGO, NAYRA C. S.; CARVALHO, BRUNA T. S.; SILVA, I, FRANCISCO; SOUSA, JOSE A.; RAMOS, RICARDO M.; PASSOS, IONARA N. G.; DE MORAES, JOSUE; LEITE, JOSE R. S. A.; LIMA, FRANCISCO C. A.. Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. PLoS One, v. 13, n. 6, . (16/22488-3)
SESSA, DEBORAH P.; MENGARDA, ANA C.; SIMPLICIO, PAULA E.; ANTAR, GUILHERME M.; LAGO, JOAO HENRIQUE G.; DE MORAES, JOSUE. 15 beta-Senecioyl-oxy-ent-kaur-16-en-19-oic Acid, a Diterpene Isolated from Baccharis lateralis, as Promising Oral Compound for the Treatment of Schistosomiasis. Journal of Natural Products, v. 83, n. 12, p. 3744-3750, . (16/22488-3, 18/07885-1)
CARNAUBA, PAULO U.; MENGARDA, ANA C.; RODRIGUES, VINICIUS C.; MORAIS, THIAGO R.; DE OLIVEIRA, ALBERTO; LAGO, JOAO HENRIQUE G.; DE MORAES, JOSUE. Evaluation of Gibbilimbol B, Isolated from Piper malacophyllum (Piperaceae), as an Antischistosomal Agent. CHEMISTRY & BIODIVERSITY, v. 18, n. 10, . (16/22488-3, 19/25289-0, 21/02789-7, 19/25905-2)
MENGARDA, ANA C.; SILVA, MARCOS P.; CIRINO, MARIA E.; MORAIS, THIAGO R.; CONSERVA, GEANNE A. A.; LAGO, JOAO HENRIQUE G.; DE MORAES, JOSUE. Licarin A, a neolignan isolated from Nectandra oppositifolia Nees & Mart. (Lauraceae), exhibited moderate preclinical efficacy against Schistosoma mansoni infection. Phytotherapy Research, v. 35, n. 9, p. 5154-5162, . (16/22488-3, 18/07885-1, 19/25289-0, 19/25905-2)
DE BRITTO, MARIANA G.; MENGARDA, ANA C.; OLIVEIRA, GEORGE L.; CIRINO, MARIA E.; SILVA, TAIS C.; DE OLIVEIRA, ROSIMEIRE N.; ALLEGRETTI, SILMARA M.; DE MORAES, JOSUE. Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection. Antimicrobial Agents and Chemotherapy, v. 64, n. 11, . (16/22488-3)
ALEIXO DE CARVALHO, LARA SOARES; QUEIROZ, LUCAS SALES; ALVES JUNIOR, ISMAEL JOSE; ALMEIDA, AYLA DAS CHAGAS; COIMBRA, ELAINE SOARES; PINTO, PRISCILA DE FARIA; NASCIMENTO DA SILVA, MARCOS PAULO; DE MORAES, JOSUE; DA SILVA FILHO, ADEMAR A.. In Vitro Schistosomicidal Activity of the Alkaloid-Rich Fraction from Ruta graveolens L. (Rutaceae) and Its Characterization by UPLC-QTOF-MS. Evidence-based Complementary and Alternative Medicine, v. 2019, . (16/22488-3)
ROQUINI, DANIEL B.; COGO, RAMON M.; MENGARDA, ANA C.; MAZLOUM, SUSANA F.; MORAIS, CRISTIANE S.; XAVIER, ROGERIO P.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; FERREIRA, LUIZ E.; PINTO, PEDRO L.; et al. Promethazine Exhibits Antiparasitic Properties In Vitro and Reduces Worm Burden, Egg Production, Hepatomegaly, and Splenomegaly in a Schistosomiasis Animal Model. Antimicrobial Agents and Chemotherapy, v. 63, n. 12, . (16/22488-3)
DE BRITO, MARIA R. M.; PELAEZ, WALTER J.; FAILLACE, MARTIN S.; MILITAO, GARDENIA C. G.; ALMEIDA, JACKSON R. G. S.; ARGUELLO, GUSTAVO A.; SZAKONYI, ZSOLT; FULOP, FERENC; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; et al. Cyclohexene-fused 1,3-oxazines with selective antibacterial and antiparasitic action and low cytotoxic effects. TOXICOLOGY IN VITRO, v. 44, p. 273-279, . (16/22488-3)
SILVA TORRES, DANIEL; ALVES DE OLIVEIRA, BRUNA; SILVEIRA, LIGIA D SOUZA; PAULO DA SILVA, MARCOS; RODRIGUES DURAES PEREIRA, VINICIUS; MORAES, JOSUE; RUBIA COSTA COURI, MARA; QUEIROZ, RAFAELLA FORTINI GRENFELL E; MARTINS PARREIRAS, PATRICIA; ROBERTO SILVA, MARCIO; et al. ynthetic Aurones: New Features for Schistosoma mansoni Therap. CHEMISTRY & BIODIVERSITY, v. 18, n. 11, . (16/22488-3)
QUEIROZ, LUCAS S.; FERREIRA, EVERTON ALLAN; MENGARDA, ANA C.; ALMEIDA, AYLA DAS C.; PINTO, PRISCILA DE F.; COIMBRA, ELAINE S.; DE MORAES, JOSUE; DENADAI, ANGELO M. L.; DA SILVA FILHO, ADEMAR A.. In vitro and in vivo evaluation of cnicin from blessed thistle (Centaurea benedicta) and its inclusion complexes with cyclodextrins against Schistosoma mansoni. Parasitology Research, v. 120, n. 4, . (16/22488-3)
DEMATEI, ANDERSON; NUNES, JOAO B.; MOREIRA, DANIEL C.; JESUS, JESSICA A.; LAURENTI, MARCIA D.; MENGARDA, ANA C. A.; VIEIRA, MARIA SILVA; DO AMARAL, CONSTANCA PAIS; DOMINGUES, MARCO M.; DE MORAES, JOSUE; et al. Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox). Journal of Natural Products, v. 84, n. 6, p. 1787-1798, . (19/25905-2, 18/24077-6, 16/22488-3)
SILVA, LIVIA MARA; MARCONATO, DANIELLE GOMES; NASCIMENTO DA SILVA, MARCOS PAULO; BARBOSA RAPOSO, NADIA REZENDE; SILVA FACCHINI, GABRIELA DE FARIA; MACEDO, GILSON COSTA; TEIXEIRAS, FERNANDA DE SA; BARBOSA DA SILVEIRA SALVADORI, MARIA CECILIA; PINTO, PRISCILA DE FARIA; DE MORAES, JOSUE; et al. icochalcone A-loaded solid lipid nanoparticles improve antischistosomal activity in vitro and in viv. Nanomedicine, v. 16, n. 19, . (16/22488-3)
PEREIRA, VINICIUS R. D.; DA SILVEIRA, LIGIA S.; MENGARDA, ANA C.; ALVES JUNIOR, ISMAEL J.; ZUZA DA SILVA, OHANA OLIVEIRA; MIGUEL, FABIO BALBINO; SILVA, MARCOS P.; ALMEIDA, AYLA DAS C.; TORRES, DANIEL DA SILVA; PINTO, PRISCILA DE F.; et al. Antischistosomal properties of aurone derivatives against juvenile and adult worms of Schistosoma mansoni. Acta Tropica, v. 213, . (16/22488-3)
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., . (16/22488-3, 14/50316-7, 14/02282-6)
COSTA, DANILO DE SOUZA; LEAL, CARLA MONTEIRO; CAJAS, RAYSSA A.; GAZOLLA, MATHEUS COUTINHO; SILVA, LIVIA MARA; DE CARVALHO, LARA SOARES ALEIXO; LEMES, BRUNA L.; DE MOURA, RENATO OLIVEIRA; DE ALMEIDA, JULIANA; DE MORAES, JOSUE; et al. Antiparasitic properties of 4-nerolidylcatechol from Pothomorphe umbellata (L.) Miq. (Piperaceae) in vitro and in mice models with either prepatent or patent Schistosoma mansoni infections. Journal of Ethnopharmacology, v. 313, p. 11-pg., . (20/01441-4, 16/22488-3)
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)
LAGO, ELOI M.; SILVA, MARCOS P.; QUEIROZ, TALITA G.; MAZLOUMA, SUSANA F.; RODRIGUES, VINICIUS C.; CARNAUBA, PAULO U.; PINTO, PEDRO L.; ROCHA, JEFFERSON A.; FERREIRA, LEONARDO L. G.; ANDRICOPULO, ADRIANO D.; et al. Phenotypic screening of nonsteroidal anti-inflammatory drugs identified mefenamic acid as a drug for the treatment of schistosomiasis. EBIOMEDICINE, v. 43, p. 370-379, . (16/22488-3, 13/07600-3)
ROQUINI, VINICIUS; MENGARDA, ANA C. C.; CAJAS, RAYSSA A. A.; MARTINS-DA-SILVA, MILENE F. F.; GODOY-SILVA, JULIA; SANTOS, GUSTAVO A. A.; ESPIRITO-SANTO, MARIA CRISTINA C.; PAVANI, THAIS F. A.; MELO, VANUSA A. A.; SALVADORI, MARIA C. C.; et al. The Existing Drug Nifuroxazide as an Antischistosomal Agent: In Vitro, In Vivo, and In Silico Studies of Macromolecular Targets. MICROBIOLOGY SPECTRUM, v. N/A, p. 12-pg., . (20/01441-4, 19/25905-2, 19/26686-2, 16/22488-3)
SILVA, TAIS C.; MENGARDA, ANA C.; SILVA, BIANCA C.; RELVAS-LIMA, THAIS S.; RODRIGUES, VINICIUS C.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; LOPES, ANDREY F. S.; RANDO, DANIELA G. G.; MORAES, JOSUE DE. New evidence for tamoxifen as an antischistosomal agent: in vitro, in vivo and target fishing studies. Future Medicinal Chemistry, v. 13, n. 11, . (16/22488-3, 19/25905-2, 19/25289-0)
ALEIXO DE CARVALHO, LARA SOARES; SILVA, LIVIA MARA; DE SOUZA, VINICIUS CARIUS; NASCIMENTO DA SILVA, MARCOS PAULO; CAPRILES, PRISCILA V. S. Z.; PINTO, PRISCILA DE FARIA; DE MORAES, JOSUE; DA SILVA FILHO, ADEMAR ALVES. Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase. CHEMISTRY & BIODIVERSITY, v. 18, n. 11, . (16/22488-3)
MENGARDA, ANA C.; SILVA, MARCOS P.; CIRINO, MARIA E.; MORAIS, THIAGO R.; CONSERVA, GEANNE A. A.; LAGO, JOAO HENRIQUE G.; DE MORAES, JOSUE. Licarin A, a neolignan isolated from Nectandra oppositifolia Nees & Mart. (Lauraceae), exhibited moderate preclinical efficacy against Schistosoma mansoni infection. Phytotherapy Research, . (16/22488-3, 19/25289-0, 19/25905-2, 18/07885-1)
MENGARDA, ANA C.; MENDONCA, POLIANA S.; MORAIS, CRISTIANE S.; COGO, RAMON M.; MAZLOUM, SUSANA F.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; MORAIS, THIAGO R.; ANTAR, GUILHERME M.; LAGO, JOAO HENRIQUE G.; et al. Antiparasitic activity of piplartine (piperlongumine) in a mouse model of schistosomiasis. Acta Tropica, v. 205, . (18/07885-1, 16/22488-3)
PORTO, RAQUEL; MENGARDA, ANA C.; CAJAS, RAYSSA A.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; ARCANJO, DANIEL D. R.; SIYADATPANAH, ABOLGHASEM; PEREIRA, MARIA DE LOURDES; WILAIRATANA, POLRAT; DE MORAES, JOSUE. Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni. PHARMACEUTICALS, v. 14, n. 7, . (16/22488-3)
XAVIER, ROGERIO P.; MENGARDA, ANA C.; SILVA, MARCOS P.; ROQUINI, DANIEL B.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; PINTO, PEDRO L.; MORAIS, THIAGO R.; FERREIRA, LEONARDO L. G.; ANDRICOPULO, ADRIANO D.; et al. H1-antihistamines as antischistosomal drugs: in vitro and in vivo studies. PARASITES & VECTORS, v. 13, n. 1, . (16/22488-3)
COSTA, POLIANA DA SILVA; ZUZA DA SILVA, OHANA OLIVEIRA; COSTA, DANILO DE SOUZA; SILVA, LARA APARECIDA DE OLIVEIRA; DE FARIA PINTO, PRISCILA; SILVA, MARCOS PAULO NASCIMENTO DA; DE MORAES, JOSUE; DA SILVA FILHO, ADEMAR A.. Assessment of the In Vitro Antischistosomal Activities of the Extracts and Compounds from Solidago Microglossa DC (Asteraceae) and Aristolochia Cymbifera Mart. & Zucc. (Aristolochiaceae). Evidence-based Complementary and Alternative Medicine, v. 2020, . (16/22488-3)
GUERRA, RAFAEL A.; SILVA, MARCOS P.; SILVA, TAIS C.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; DE OLIVEIRA, ROSIMEIRE N.; ROCHA, JEFFERSON A.; PINTO, PEDRO L. S.; DE MORAES, JOSUE. In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing. Antimicrobial Agents and Chemotherapy, v. 63, n. 3, . (16/22488-3)
LAGO, ELOI M.; XAVIER, ROGERIO P.; TEIXEIRA, THAINA R.; SILVA, LIVIA M.; DA SILVA FILHO, ADEMAR A.; DE MORAES, JOSUE. Antischistosomal agents: state of art and perspectives. Future Medicinal Chemistry, v. 10, n. 1, p. 89-120, . (16/22488-3)
SILVA, BIANCA C.; MENGARDA, ANA C.; RODRIGUES, VINICIUS C.; CAJAS, RAYSSA A.; CARNAUBA, PAULO U.; ESPIRITO-SANTO, MARIA CRISTINA C.; BEZERRA-FILHO, CARLOS S. M.; DE SOUSA, DAMIAO P.; DE MORAES, JOSUE. Efficacy of carvacryl acetate in vitro and following oral administration to mice harboring either prepatent or patent Schistosoma mansoni infections. Parasitology Research, v. 120, n. 11, . (19/25905-2, 16/22488-3, 19/25289-0)
RANDO, DANIELA G. G.; DA COSTA, MARCELA O. L.; PAVANI, THAIS F. A.; OLIVEIRA, THIAGO; DOS SANTOS, PALOMA F.; AMORIM, CARINA R.; PINTO, PEDRO L. S.; DE BRITO, MARIANA G.; SILVA, MARCOS P. N.; ROQUINI, DANIEL B.; et al. Vanillin-Related N-Acylhydrazones: Synthesis, Antischistosomal Properties and Target Fishing Studies. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 19, n. 14, p. 1241-1251, . (16/22488-3)
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, . (16/22488-3, 14/02282-6)
DIAS, MIRNA MEANA; ZUZA, OHANA; RIANI, LORENA R.; PINTO, PRISCILA DE FARIA; SILVA PINTO, PEDRO LUIZ; SILVA, MARCOS P.; DE MORAES, JOSUE; ATAIDE, ANA CAROLINE Z.; SILVA, FERNANDA DE OLIVEIRA; CECILIO, ALZIRA BATISTA; et al. In vitro schistosomicidal and antiviral activities of Arctium lappa L. (Asteraceae) against Schistosoma mansoni and Herpes simplex virus-1. BIOMEDICINE & PHARMACOTHERAPY, v. 94, p. 489-498, . (16/22488-3)
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, . (16/22488-3, 14/02282-6, 14/50316-7)
PEREIRA, VINICIUS R. D.; ALVES JUNIOR, ISMAEL J.; DA SILVEIRA, LIGIA S.; GERALDO, REINALDO B.; PINTO, PRISCILA DE F.; TEIXEIRA, FERNANDA S.; SALVADORI, MARIA C.; SILVA, MARCOS P.; ALVES, LARA A.; CAPRILES, PRISCILA V. S. Z.; et al. In Vitro and in Vivo Antischistosomal Activities of Chalcones. CHEMISTRY & BIODIVERSITY, v. 15, n. 12, . (16/22488-3)
ROQUINI, DANIEL B.; SILVA, GABRIEL L.; FERREIRA, LEONARDO L. G.; ANDRICOPULO, ADRIANO D.; WILAIRATANA, POLRAT; DE MORAES, JOSUE. Susceptibility of Angiostrongylus cantonensis Larvae to Anthelmintic Drugs. FRONTIERS IN PHARMACOLOGY, v. 13, p. 9-pg., . (13/07600-3, 16/22488-3, 20/01441-4)

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