Mitochondrial Imbalance of Trypanosoma cruzi Induced by the Marine Alkaloid 6-Bromo-2′-de- N-Methylaplysinopsin

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Autor(es): dc.contributorAdolfo Lutz Institute-
Autor(es): dc.contributorUniversidade Federal do ABC (UFABC)-
Autor(es): dc.contributorInstituto Adolfo Lutz-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorRomanelli, Maiara M.-
Autor(es): dc.creatorAmaral, Maiara-
Autor(es): dc.creatorThevenard, Fernanda-
Autor(es): dc.creatorSanta Cruz, Lucas M.-
Autor(es): dc.creatorRegasini, Luis O.-
Autor(es): dc.creatorMigotto, Alvaro E.-
Autor(es): dc.creatorLago, João Henrique G.-
Autor(es): dc.creatorTempone, Andre G.-
Data de aceite: dc.date.accessioned2025-08-21T15:42:51Z-
Data de disponibilização: dc.date.available2025-08-21T15:42:51Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-08-16-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1021/acsomega.2c03395-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241698-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241698-
Descrição: dc.descriptionChagas disease, caused by Trypanosoma cruzi, affects seven million people worldwide and lacks effective treatments. Using bioactivity-guided fractionation, NMR, and electrospray ionization-high resolution mass spectrometry (ESI-HRMS) spectral analysis, the indole alkaloid 6-bromo-2′-de-N-methylaplysinopsin (BMA) was isolated and chemically characterized from the marine coral Tubastraea tagusensis. BMA was tested against trypomastigotes and intracellular amastigotes of T. cruzi, resulting in IC50 values of 62 and 5.7 μM, respectively, with no mammalian cytotoxicity. The mechanism of action studies showed that BMA induced no alterations in the plasma membrane permeability but caused depolarization of the mitochondrial membrane potential, reducing ATP levels. Intracellular calcium levels were also reduced after the treatment, which was associated with pH alteration of acidocalcisomes. Using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)/MS analysis, alterations of mass spectral signals were observed after treatment with BMA, suggesting a different mechanism from benznidazole. In silico pharmacokinetic-pharmacodynamic (PKPD) parameters suggested a drug-likeness property, supporting the promising usefulness of this compound as a new hit for optimizations.-
Descrição: dc.descriptionCentre for Parasitology and Mycology Adolfo Lutz Institute, Av Dr Arnaldo 351, SP-
Descrição: dc.descriptionCentre of Natural Sciences and Humanities Federal University of ABC (UFABC), Avenida dos Estados 5001, SP-
Descrição: dc.descriptionDepartment of Organic Contaminants Instituto Adolfo Lutz, Av Dr Arnaldo 355, SP-
Descrição: dc.descriptionDepartment of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences Universidade Estadual Paulista, R. Cristóvão Colombo 2265, SP-
Descrição: dc.descriptionCentre for Marine Biology Universidade de São Paulo, Rodovia Manoel Hypólito do Rego, Km 131, São Sebastião, SP-
Descrição: dc.descriptionDepartment of Chemistry and Environmental Sciences Institute of Biosciences Humanities and Exact Sciences Universidade Estadual Paulista, R. Cristóvão Colombo 2265, SP-
Formato: dc.format28561-28570-
Idioma: dc.languageen-
Relação: dc.relationACS Omega-
???dc.source???: dc.sourceScopus-
Título: dc.titleMitochondrial Imbalance of Trypanosoma cruzi Induced by the Marine Alkaloid 6-Bromo-2′-de- N-Methylaplysinopsin-
Tipo de arquivo: dc.typelivro digital-
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