Study of the genotoxicological potential and permeation assay with Caco-2 cells of metallic complexes with promising biological activities

• Grant number: 17/16278-9
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2018 - July 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Flávia Aparecida Resende Nogueira
• Grantee: Flávia Aparecida Resende Nogueira
• Host Institution: Universidade de Araraquara (UNIARA). Associação São Bento de Ensino. Araraquara , SP, Brazil

Abstract

This research project aims to evaluate the cytotoxic and mutagenic activities of metal complexes by different mechanisms of interaction with the genetic material, as well as permeation tests in colon carcinoma cells (Caco-2). Considering that medicinal inorganic chemistry represents a field of great promise, with potential for expansion due to chemical diversity and reactivity of metals, in addition to predict the safety and efficacy in a future therapeutic use, this project may also point to substances with positive mutagenicity at further studies, leading them to perform more specific and sophisticated tests, since the chemical agents used for the treatment of tumors, for example, are usually cytotoxic and mutagenic. Studies on the mechanism of action of these complexes become important so that their real clinical potential can be defined, contributing to the development of a new drug with selectivity, in order to minimize the side effects. The present study can be developed with an inter and multidisciplinary character, with collaborations that could result in great advances from the scientific point of view. Initially, complexes of copper (II), silver (I), platinum (II), palladium (II) and gold (I) with isoniazid, furosemide, indapamide, chlorthalidone and hydrochlorothiazide will be evaluated, some of them were included in project FAPESP (Proc: 2015 / 09833-0) under the coordination of Prof Dr Wilton Rogério Lustri, others produced and supplied by Prof Dr Antônio Carlos Massabni, professor at the University of Araraquara and by postdoctoral Dr Patrícia Bento Silva of the research group on Coordination Chemistry and Organometallic of the Institute of Chemistry of Araraquara - UNESP. These complexes were previously selected by show promising antibacterial or antitumor activity. In order to verify the safety for genetic material and human health, the objectives of this work are based on the study of cytotoxicity by the resazurin method (Alamar Blue), trypan blue and clonogenic survival in normal and tumor cells, in order to obtain the index of selectivity, and the ability to apoptosis induction. In addition, they will continue to analyze mutagenicity by Ames, Micronucleus and Comet in vitro tests and permeation tests on Caco-2 cell monolayers, due to the importance of pharmacokinetic knowledge of new drugs. (AU)

Scientific publications

(17)

(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)

MARENA, GABRIEL DAVI; GIROTTO, LUIZA; SALDANHA, LUIZ LEONARDO; RAMOS, MATHEUS APARECIDO DOS SANTOS; DE GRANDIS, RONE APARECIDO; DA SILVA, PATRICIA BENTO; DOKKEDAL, ANNE LIGIA; CHORILLI, MARLUS; BAUAB, TAIS MARIA; PAVAN, FERNANDO ROGERIO; et al. Hydroalcoholic Extract of Myrcia bella Loaded into a Microemulsion System: A Study of Antifungal and Mutagenic Potential. Planta Medica, JAN 2021. (16/08559-5, 17/16278-9, 18/12590-0, 17/18782-6)

FREGONEZI, NATHALIA FERREIRA; DE SOUZA, FABIANA APARECIDA; ALEIXO, NADIA ANDRADE; DA SILVA GOMES, PIETRA STEFANY; SILVESTRE, RAFAELA BALDASSARI; DE GRANDIS, RONE APARECIDO; DA SILVA, PATRICIA BENTO; PAVAN, FERNANDO ROGERIO; CHORILLI, MARLUS; RESENDE, FLAVIA APARECIDA. Cyto-genotoxic evaluation of novel anti-tubercular copper (II) complexes containing isoniazid-based ligands. REGULATORY TOXICOLOGY AND PHARMACOLOGY, v. 113, JUN 2020. (17/16278-9)

DE GRANDIS, RONE APARECIDO; COSTA, ANALU ROCHA; FERREIRA MORAES, CARLOS ANDRE; SAMPAIO, NATALIA ZANETI; CERQUEIRA, IGOR HENRIQUE; MARQUES, WELLINGTON GARCIA; MUNDIN GUEDES, ADRIANA PEREIRA; DE ARAUJO-NETO, JOAO HONORATO; PAVAN, FERNANDO ROGERIO; DEMIDOFF, FELIPE CERQUEIRA; et al. Novel Ru(II)-bipyridine/phenanthroline-lapachol complexes as potential anti-cancer agents. Journal of Inorganic Biochemistry, v. 237, p. 12-pg., 2022-12-01. (16/22429-7, 17/15850-0, 17/16278-9, 20/14561-8, 21/04876-4)

ALEIXO, NADIA ANDRADE; GOMES, PIETRA STEFANY DA SILVA; DA SILVA, PATRICIA BENTO; SATO, MARIANA RILLO; CAMPOS, DEBORA LEITE; BARUD, HERNANE DA SILVA; CASTRO, GUILLERMO RAUL; ISLAN, GERMAN ABEL; TOLEDO, CONSTANZA; KARP, FEDERICO; et al. tudy of antimycobacterial, cytotoxic, and mutagenic potential of polymeric nanoparticles of copper (II) comple. Journal of Microencapsulation, v. 39, n. 1, p. 61-71, JAN 2 2022. (13/09265-7, 17/16278-9)

MANZANO, CARLOS M.; NAKAHATA, DOUGLAS H.; TENORIO, JUAN C.; LUSTRI, WILTON R.; RESENDE NOGUEIRA, FLAVIA A.; ALEIXO, NADIA A.; DA SILVA GOMES, PIETRA S.; PAVAN, FERNANDO R.; GRECCO, JULIA A.; RIBEIRO, CAMILA M.; et al. Silver complexes with fluoroanthranilic acid isomers: Spectroscopic characterization, antimycobacterial activity and cytotoxic studies over a panel of tumor cells. Inorganica Chimica Acta, v. 502, MAR 1 2020. (18/00163-0, 18/12062-4, 17/16278-9, 17/25995-6)

LUSTRI, WILTON R.; LAZARINI, SILMARA C.; AQUARONI, NAYARA AP SIMEI; RESENDE, FLAVIA A.; ALEIXO, NADIA A.; PEREIRA, DOUGLAS H.; LUSTRI, BRUNA CARDINALI; MOREIRA, CRISTIANO GALLINA; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; et al. A new complex of silver(I) with probenecid: Synthesis, characterization, and studies of antibacterial and extended spectrum beta-lactamases (ESBL) inhibition activities. Journal of Inorganic Biochemistry, v. 243, p. 12-pg., 2023-03-30. (18/00163-0, 19/03049-7, 15/09833-0, 15/20882-3, 18/12062-4, 17/16278-9, 21/07458-9, 17/19243-1, 20/13497-4, 18/12590-0, 19/26696-8, 18/00187-7, 21/08717-8, 18/02344-2)

PIZI CANDIDO, AMANDA DE LIMA; FREGONEZI, NATHALIA FERREIRA; CARVALHO, ANTONIO JOSE FELIX; TROVATTI, ELIANE; RESENDE, FLAVIA APARECIDA. TEMPO-Oxidized Cellulose Nanofibers In Vitro Cyto-genotoxicity Studies. BIONANOSCIENCE, v. 10, n. 3, p. 7-pg., 2020-06-11. (17/16278-9)

MARENA, GABRIEL DAVI; GIROTTO, LUIZA; SALDANHA, LUIZ LEONARDO; RAMOS, MATHEUS APARECIDO DOS SANTOS; DE GRANDIS, RONE APARECIDO; DA SILVA, PATRICIA BENTO; DOKKEDAL, ANNE LIGIA; CHORILLI, MARLUS; BAUAB, TAIS MARIA; PAVAN, FERNANDO ROGERIO; et al. Hydroalcoholic Extract of Myrcia bella Loaded into a Microemulsion System: A Study of Antifungal and Mutagenic Potential. Planta Medica, v. 88, n. 05, p. 11-pg., 2021-01-28. (17/18782-6, 17/16278-9, 18/12590-0, 16/08559-5)

PIZI CANDIDO, AMANDA DE LIMA; FREGONEZI, NATHALIA FERREIRA; CARVALHO, ANTONIO JOSE FELIX; TROVATTI, ELIANE; RESENDE, FLAVIA APARECIDA. TEMPO-Oxidized Cellulose Nanofibers In Vitro Cyto-genotoxicity Studies. BIONANOSCIENCE, JUN 2020. (17/16278-9)

DOS SANTOS PEREIRA, ANNA KARLA; SANTOS, IGOR A.; DA SILVA, WASHINGTON W.; RESENDE NOGUEIRA, FLAVIA A.; BERGAMINI, FERNANDO R. G.; JARDIM, ANA CAROLINA G.; CORBI, PEDRO P.. Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?. PHARMACOLOGICAL REPORTS, v. 73, n. 3, FEB 2021. (18/12062-4, 17/16278-9)

SIMEI AQUARONI, NAYARA AP.; NAKAHATA, DOUGLAS H.; LAZARINI, SILMARA C.; RESENDE, FLAVIA A.; CANDIDO, AMANDA L. P.; BARUD, HERNANE DA SILVA; CLARO, AMANDA MARIA; DE CARVALHO, JOAO ERNESTO; RIBEIRO, CAMILA M.; PAVAN, FERNANDO R.; et al. Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support. Journal of Inorganic Biochemistry, v. 212, NOV 2020. (17/19243-1, 15/09833-0, 17/16278-9, 18/12062-4, 16/07729-4, 13/07276-1, 18/12590-0, 18/25512-8, 14/06779-2, 19/03049-7, 18/02344-2, 18/00163-0, 15/20882-3)

LIMA NETO, JOSE DE SOUSA; MARENA, GABRIEL DAVI; GIROTTO, LUIZA; MAGORPO, VANESSA; DOS SANTOS RAMOS, MATHEUS APARECIDO; DA SILVA, PATRICIA BENTO; CHORILLI, MARLUS; BAUAB, TAIS MARIA; RESENDE, FLAVIA APARECIDA. Biological Properties of Extracts from Byrsonima Species in Microemulsions. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 32, n. 3, p. 6-pg., 2022-04-29. (19/06818-1, 17/16278-9, 18/01381-1)

BARRETO, MARIANA RODRIGUES; ALEIXO, NADIA ANDRADE; SILVESTRE, RAFAELA BALDASSARI; FREGONEZI, NATHALIA FERREIRA; BARUD, HERNANE DA SILVA; DIAS, DIOGENES DOS SANTOS; RIBEIRO, CLOVIS AUGUSTO; RESENDE, FLAVIA APARECIDA. Genotoxicological safety assessment of puree-only edible films from onion bulb (Allium cepa L.) for use in food packaging-related applications. Journal of Food Science, v. 85, n. 1, DEC 2019. (17/16278-9)

GONCALVES, ISABELLA SALGADO; LIMA, LAIS RONCALHO; BERRETTA, ANDRESA APARECIDA; AMORIM, NATHALY ALCAZAR; PRATAVIEIRA, SEBASTIAO; CORREA, THAILA QUATRINI; RESENDE NOGUEIRA, FLAVIA APARECIDA; BARUD, HERNANE SILVA. Antimicrobial Formulation of a Bacterial Nanocellulose/Propolis-Containing Photosensitizer for Biomedical Applications. POLYMERS, v. 15, n. 4, p. 20-pg., 2023-02-01. (13/07793-6, 17/16278-9, 18/25512-8, 09/54035-4)

BARBOSA, LORRANA VIETRO; CASTRO, MONA STEFANY DE SOUZA; CIUFFI, KATIA JORGE; NASSAR, EDUARDO J.; MARCAL, LIZIANE; PEREIRA, LORENA RODRIGUES; SANTOS, MARIO FERREIRA CONCEICAO; AMBROSIO, SERGIO RICARDO; GOMES, PIETRA STEFANY DA SILVA; NOGUEIRA, FLAVIA APARECIDA RESENDE; et al. Kaolinite-titanium nanocomposite applied to the photodegradation of the genotoxic compound cisplatin and the terephthalic acid hydroxylation reaction. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 676, p. 12-pg., 2023-11-05. (17/15482-1, 18/05080-6, 18/25010-2, 11/09823-4, 17/16278-9, 11/09823-4, 19/26439-5, 20/06712-6, 16/01501-1)

DA SILVA GOMES, PIETRA STEFANY; DA SILVA, WASHINGTON WILSON; GASPAROTI, GABRIELA DE CASSIA; PAYOLLA, FILIPE BOCCATO; DE OLIVEIRA, JONATA AUGUSTO; BARBUGLI, PAULA ABOUD; MARIN-DETT, FREDDY HUMBERTO; CAVICCHIOLI, MAURICIO; MASSABNI, ANTONIO CARLOS; RESENDE, FLAVIA APARECIDA. Evaluation of cytotoxicity and genotoxicity of a novel oxovanadium complex with orotate. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, v. 883, p. 7-pg., 2022-11-01. (17/16278-9, 13/09265-7)

IGOR HENRIQUE CERQUEIRA; MARIA JULIA MIELI; ANNA KARLA DOS SANTOS PEREIRA; PEDRO PAULO CORBI; FLAVIA APARECIDA RESENDE. EVALUATION OF THE CYTOTOXICITY AND GENOTOXICOLOGICAL SAFETY PROFILE OF BIOACTIVE SILVER(I) COMPLEXES WITH AMINOADAMANTANE LIGANDS. Química Nova, v. 47, n. 6, 2024-03-11. (21/08717-8, 17/16278-9, 21/10265-8)