ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics

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Autor(es): dc.contributorFederal University of Mato Grosso do Sul-
Autor(es): dc.contributorNorth Dakota State University-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorInstituto Federal de Mato Grosso do Sul-
Autor(es): dc.contributorUniversidade Federal de Minas Gerais (UFMG)-
Autor(es): dc.contributorFluminense Federal University-
Autor(es): dc.creatorOliveira, Rodrigo Juliano-
Autor(es): dc.creatorda Silveira, Ingridhy Ostaciana Maia Freitas-
Autor(es): dc.creatordas Neves, Silvia C.-
Autor(es): dc.creatorMitsuyasu, Barbara-
Autor(es): dc.creatorMartins, Allana C.-
Autor(es): dc.creatorBerno, Claudia-
Autor(es): dc.creatorMohammad, Jiyan-
Autor(es): dc.creatorRaj, Halie-
Autor(es): dc.creatorde Araujo, Flavio H. S.-
Autor(es): dc.creatorHortelan, Cristiane Regina-
Autor(es): dc.creatorMachado, Luana-
Autor(es): dc.creatorda Silva Júnior, Eufrânio N.-
Autor(es): dc.creatorVilela, Marcelo L. B.-
Autor(es): dc.creatorNascimento, Valter Aragão-
Autor(es): dc.creatorBeatriz, Adilson-
Autor(es): dc.creatorda Silva Gomes, Roberto-
Data de aceite: dc.date.accessioned2025-08-21T16:17:57Z-
Data de disponibilização: dc.date.available2025-08-21T16:17:57Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-01-15-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1021/acs.chemrestox.2c00275-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/246546-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/246546-
Descrição: dc.descriptionCancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of ZIM, a candidate for chemotherapy, and 4-AA alone and in association with commercial chemotherapeutic agents. Subsequently, the results of ZIM and 4-AA were compared. Male Swiss mice were treated with doses of 12, 24, or 48 mg/kg ZIM or 4-AA alone or in association with cisplatin (6 mg/kg), doxorubicin (16 mg/kg), and cyclophosphamide (100 mg/kg). Biometric parameters, DNA damage (comet and micronuclei), cell death, and splenic phagocytosis were evaluated. DNA docking was also performed to confirm the possible interactions of ZIM and 4-AA with DNA. 4-AA has been shown to have low genotoxic potential, increase the frequency of cell death, and activate phagocytosis. ZIM causes genomic and chromosomal damage in addition to causing cell death and activating phagocytosis. In association with chemotherapeutical agents, both 4-AA and ZIM have a chemopreventive effect and, therefore, reduce the frequency of DNA damage, cell death, and splenic phagocytosis. The association of 4-AA and ZIM with commercial chemotherapeutic agents increased the frequency of lymphocytes compared to chemotherapeutic agents alone. Molecular docking demonstrated that ZIM has more affinity for DNA than 4-AA and its precursors (1 and 2). This was confirmed by the lower interaction energy of the complex (−119.83 kcal/mol). ZIM can break the DNA molecule and, therefore, its chemotherapeutic effect can be related to DNA damage. It is considered that ZIM has chemotherapeutic potential. However, it should not be used in combination with cisplatin, doxorubicin, and cyclophosphamide as it reduces the effects of these drugs.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)-
Descrição: dc.descriptionNorth Dakota State University-
Descrição: dc.descriptionStem Cell Cell Therapy and Toxicological Genetics Research Centre (CeTroGen) Medical School Federal University of Mato Grosso do Sul, Mato Grosso do Sul-
Descrição: dc.descriptionGraduate Program in Health and Development in the Midwest Region Medical School Federal University of Mato Grosso do Sul, Mato Grosso do Sul-
Descrição: dc.descriptionInstitute of Chemistry Federal University of Mato Grosso do Sul, Mato Grosso do Sul-
Descrição: dc.descriptionDepartment of Pharmaceutical Sciences North Dakota State University-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP), SP-
Descrição: dc.descriptionInstituto Federal de Mato Grosso do Sul, MS-
Descrição: dc.descriptionInstitute of Exact Sciences Department of Chemistry Federal University of Minas Gerais, MG-
Descrição: dc.descriptionDepartment of Chemistry Fluminense Federal University, RJ-
Descrição: dc.descriptionMedical School Federal University of Mato Grosso do Sul, Mato Grosso do Sul-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP), SP-
Formato: dc.format66-82-
Idioma: dc.languageen-
Relação: dc.relationChemical Research in Toxicology-
???dc.source???: dc.sourceScopus-
Título: dc.titleZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics-
Tipo de arquivo: dc.typelivro digital-
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