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Studies on structure & activity of RuII / arene / mercaptoligants complexes against cancer

Grant number: 21/04876-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2021
Effective date (End): April 30, 2023
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Acordo de Cooperação: CNPq - Pronex
Principal Investigator:Javier Alcides Ellena
Grantee:João Honorato de Araujo Neto
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:17/15850-0 - X-ray diffraction as a tool in potential drug development, AP.TEM
Associated research grant(s):24/09220-8 - 45th International Conference on Coordination Chemistry, AR.EXT

Abstract

The present project aim the synthesis and characterizing ruthenium II semi-sandwich complexes containing binders of biological interest, as new candidates for metallopharmaceuticals, being an integral part of the thematic project "X-Ray Diffraction as a Tool in the Development of Potential Drugs" (2017 / 15850-0). In the synthesis stage, it is intended to perform a "screening" to evaluate the viability of coordination of mercaptoligantes, which are derived from mercaptopiridines and mercaptopirimidines, with ruthenium II precursors of general formula [Ru (h6-p-cimene) Cl2]2 and [Ru (h6-p-cymene) Cl2 (P)] where P refers to monophosphines. The synthesized compounds will be characterized by techniques such as 1H, 13C and 31P {1H} nuclear magnetic resonance spectroscopy, cyclic and differential pulse voltammetry, conductometry, absorption spectroscopy in the ultraviolet / visible / infrared region and elementary analysis. In addition, he will dedicate himself to the characterization of the compounds in the solid state, mainly by the diffraction of X-rays by single crystals (equipment operation, data collection and refinement), of the structural and crystallographic properties exhibited by these complexes and others belonging to the thematic project, and from the structural information elucidate some physicochemical properties of the same. Subsequently, it is intended to study the possible interactions of these complexes with biomolecules such as: DNA and HSA. The influence of the compounds on the cell cycle, apoptosis by annexing V assay, quantification of reactive oxygen species, as well as determination of proteins related to apoptosis will also be evaluated. The results obtained will be compared with each other and with data from the literature, seeking a better understanding of the molecular regions responsible for their biological, chemical and structural properties, in order to explore how the compounds can interact with them and elucidate their mechanisms of action. (AU)

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Scientific publications (12)
(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)
ALVES, KAMILLA M.; HONORATO, JOAO; LIAO, LUCIANO M.; VELOZO-SA, VIVIANNE S.; GUEDES, ADRIANA P. M.; DUTRA, JOCELY DE L.; AYALLA, ALEJANDO P.; ELLENA, JAVIER; BATISTA, ALZIR A.; GONCALVES, PABLO J.. meso-Tetra-(4-pyridyl)porphyrin/palladium(ii) complexes as anticancer agents. DALTON TRANSACTIONS, v. 50, n. 44, . (21/02522-0, 21/04876-4, 18/19342-2, 17/15850-0)
GRAMINHA, ANGELICA E.; POPOLIN, CECILIA; DE ARAUJO-NETO, JOAO HONORATO; CORREA, RODRIGO S.; DE OLIVEIRA, KATIA M.; GODOY, LUANI R.; VEGAS, LEGNA COLINA; ELLENA, JAVIER; BATISTA, ALZIR A.; COMINETTI, MARCIA R.. New ruthenium complexes containing salicylic acid and derivatives induce triple-negative tumor cell death via the intrinsic apoptotic pathway. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 243, p. 14-pg., . (17/15850-0, 14/19632-0, 21/04876-4, 20/14561-8)
OLIVEIRA, CARLOS HENRIQUE DE MOURA; NETO, JOAO HONORATO DE ARAUJO; ELENNA, JAVIER ALCIDES; OLIVER, JOSIDEL CONCEICAO; DIAS, AMANDA LATERCIA TRANCHES; CALDAS, IVO SANTANA; DORIGUETTO, ANTONIO CARLOS. Structure and in vitro antimicrobial activity of sulfamethoxazole and sulfadiazine polyiodide salts. Journal of Molecular Structure, v. 1282, p. 15-pg., . (21/04876-4)
DE ARAUJO-NETO, JOAO HONORATO; GUEDES, ADRIANA P. M.; LEITE, CELISNOLIA M.; MORAES, CARLOS ANDR E F.; SANTOS, ANDRESSA L.; BRITO, RAFAELLA DA S.; ROCHA, THIAGO L.; MELLO-ANDRADE, FRANCYELLI; ELLENA, JAVIER; BATISTA, ALZIR A.. ?Half-Sandwich? Ruthenium Complexes with Alizarin as Anticancer Agents: In Vitro and In Vivo Studies. Inorganic Chemistry, v. 62, n. 18, p. 15-pg., . (21/04876-4, 17/15850-0, 21/02522-0)
FIRMINO, POLLYANA P.; SANTIAGO, PEDRO H. DE O.; DA SILVA, CECILIA C. P.; DE ARAUJO-NETO, JOAO H.; ELLENA, JAVIER. The free hydralazine anti-hypertensive drug and new salts with improved solubility. Journal of Molecular Structure, v. 1291, p. 11-pg., . (21/04876-4, 21/10066-5)
SILVA, HENRIQUE VIEIRA REIS; DA SILVA, GUILHERME ALVARO FERREIRA; ZAVAN, BRUNO; MACHADO, RAFAEL PEREIRA; DE ARAUJO-NETO, JOAO HONORATO; ELLENA, JAVIER ALCIDES; IONTA, MARISA; FRAZA, MARILIA IMACULADA; DORIGUETTO, ANTONIO CARLOS. The nicotinamide ruthenium(II) complex induces the production of reactive oxygen species (ROS), cell cycle arrest, and apoptosis in melanoma cells. Polyhedron, v. 231, p. 17-pg., . (17/15850-0, 21/04876-4)
LEITE, CELISNOLIA M.; HONORATO, JOAO; MARTIN, ANA CAROLINA B. M.; SILVEIRA, RAFAEL G.; COLOMBARI, FELIPPE M.; AMARAL, JESSICA C.; COSTA, ANALU R. .; COMINETTI, MARCIA R. .; PLUTIN, ANA M.; DE AGUIAR, DEBORA; et al. xperimental and Theoretical DFT Study of Cu(I)/N,N-Disubstituted-N `-acylthioureato Anticancer Complexes: Actin Cytoskeleton and Induction of Death by Apoptosis in Triple-Negative Breast Tumor Cell. Inorganic Chemistry, . (21/04876-4, 18/19342-2)
LIMA, DEBORAH A.; BISPO JR, AIRTON G.; GALICO, DIOGO A. .; COELHO, SERGIO F. N.; NETO, JOAO H. ARAUJO; ELLENA, JAVIER A.; PETIOTE, LANOUSSE; MAZALI, ITALO O.; SIGOLI, FERNANDO A. .. Tuning the Thermometric Features in 1D Luminescent EuIII and TbIII Coordination Polymers through Different Bridge Phosphine Oxide Ligands. Inorganic Chemistry, v. 62, n. 17, p. 9-pg., . (21/04876-4, 20/02614-0, 21/08111-2, 17/08098-0, 21/06326-1)
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., . (16/22429-7, 17/15850-0, 17/16278-9, 20/14561-8, 21/04876-4)
SOUSA, CAROLINE C.; DZIWORNU, GODWIN AKPEKO; QUADROS, HELENITA C.; ARAUJO-NETO, JOAO HONORATO; CHIBALE, KELLY; MOREIRA, DIOGO R. M.. Antimalarial Pyrido[1,2-a]benzimidazoles Exert Strong Parasiticidal Effects by Achieving High Cellular Uptake and Suppressing Heme Detoxification. ACS INFECTIOUS DISEASES, v. 8, n. 8, p. 11-pg., . (21/02522-0, 21/04876-4)
FERREIRA, MILLENA P. P.; CASTRO, CAIO B. B.; HONORATO, JOAO; HE, SHENG; GUIMARAES, WALBER GONCALVES; ESMIEU, CHARLENE; CASTELLANO, EDUARDO E. E.; DE MOURA, ANDRE F.; TRUZZI, DANIELA R.; NASCIMENTO, OTACIRO R.; et al. Biomimetic catalysis of nitrite reductase enzyme using copper complexes in chemical and electrochemical reduction of nitrite. DALTON TRANSACTIONS, v. 52, n. 32, p. 11-pg., . (21/04876-4, 19/17483-0, 13/07937-8)
AKINYEMI, AMOS O.; PEREIRA, GEORGE B. S.; OLIVEIRA, GABRIELA P.; LIMA, MAURO A.; ROCHA, JOSIAS S.; COSTA, VINICIUS A.; FORTALEZA, DARIO B.; TEIXEIRA, TAMARA; ZANOTTI, KARINE; FORIM, MOACIR ROSSI; et al. Palladium (II) complexes as inhibitors of cathepsin B and topoisomerase I beta: Synthesis, characterization, and cytotoxicity. Journal of Molecular Structure, v. 1294, p. 14-pg., . (19/11242-1, 21/04876-4, 22/02876-0)

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