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Structural modifications in biologically active Ru(II) complexes toward the design of new metallodrug candidates

Grant number: 13/26559-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2014
Effective date (End): August 02, 2015
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Alzir Azevedo Batista
Grantee:Rodrigo de Souza Corrêa
Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

This research project is dedicated to obtaining and characterization of ruthenium(II) complexes containing ligands of biological interest, as new metallodrug candidates. In the first stage will be evaluated the best synthesis route, screening the feasibility of coordinating bioligands, which are derivatives of purines, pyrimidines, quinolines and derivatives of aciltioureas with ruthenium(II) precursors of general formula: [RuCl2(P)2(N-N)], where P refers to monophosphines, and N-N are diimine derivatives. The synthesized compounds will be characterized by techniques such as nuclear magnetic resonance spectroscopy (1H, 13C and 31P{1H}), cyclic and differential pulse voltammetry, conductometry, absorption spectroscopy in the ultraviolet/visible/infrared regions, elemental analysis and X-ray crystallography. Subsequently, the cytotoxicity assays with the new compounds will be carried out to evaluate their promising antitumor activities. Also, possible interactions of with biomolecules such as DNA and BSA will be studied. The obtained results will be compared with reported data in the literature, to better understand which molecular regions of the complexes are responsible for their biological properties in order to explore how the compounds can interact with them and to elucidate their mechanisms of action.

Scientific publications (9)
(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)
CORREA, RODRIGO S.; OLIVEIRA, KATIA M.; PEREZ, HIRAM; PLUTIN, ANA M.; RAMOS, RAUL; MOCELO, RAUL; CASTELLANO, EDUARDO E.; BATISTA, ALZIR A. cis-bis(N-benzoyl-N `,N `-dibenzylthioureido) platinum(II): Synthesis, molecular structure and its interaction with human and bovine serum albumin. ARABIAN JOURNAL OF CHEMISTRY, v. 12, n. 8, p. 3454-3462, DEC 2019. Web of Science Citations: 8.
CORREA, RODRIGO S.; DA SILVA, MONIZE M.; GRAMINHA, ANGELICA E.; MEIRA, CASSIO S.; DOS SANTOS, JAMYLE A. F.; MOREIRA, DIOGO R. M.; SOARES, MILENA B. P.; VON POELHSITZ, GUSTAVO; CASTELLANO, EDUARDO E.; BLOCH, JR., CARLOS; COMINETTI, MARCIA R.; BATISTA, ALZIR A. Ruthenium(II) complexes of 1,3-thiazolidine-2-thione: Cytotoxicity against tumor cells and anti-Trypanosoma cruzi activity enhanced upon combination with benznidazole. Journal of Inorganic Biochemistry, v. 156, p. 153-163, MAR 2016. Web of Science Citations: 26.
BENEDICTO A. V. LIMA; RODRIGO S. CORRÊA; ANGELICA E. GRAMINHA; ALEKSEY KUZNETSOV; JAVIER ELLENA; FERNANDO R. PAVAN; CLARICE Q. F. LEITE; ALZIR A. BATISTA. Anti-Mycobacterium tuberculosis and Cytotoxicity Activities of Ruthenium(II)/ Bipyridine/Diphosphine/Pyrimidine-2-thiolate Complexes: The Role of the Non- Coordinated N-Atom. Journal of the Brazilian Chemical Society, v. 27, n. 1, p. -, Jan. 2016.
LIMA, BENEDICTO A. V.; CORREA, RODRIGO S.; GRAMINHA, ANGELICA E.; KUZNETSOV, ALEKSEY; ELLENA, JAVIER; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; BATISTA, ALZIR A. Anti-Mycobacterium tuberculosis and Cytotoxicity Activities of Ruthenium(II)/Bipyridine/Diphosphine/Pyrimidine-2-thiolate Complexes: The Role of the Non-Coordinated N-Atom. Journal of the Brazilian Chemical Society, v. 27, n. 1, p. 30-40, JAN 2016. Web of Science Citations: 11.
DOS SANTOS, EDJANE R.; CORREA, RODRIGO S.; RIBEIRO, JULIANA U.; GRAMINHA, ANGELICA E.; ELLENA, JAVIER; SELISTRE-DE-ARAUJO, HELOISA S.; BATISTA, ALZIR A. Ru(II)/bisphosphine/diimine/amino acid complexes: diastereoisomerism, cytotoxicity, and inhibition of tumor cell adhesion to collagen type I. Journal of Coordination Chemistry, v. 69, n. 23, p. 3518-3530, 2016. Web of Science Citations: 6.
CORREA, RODRIGO S.; DE OLIVEIRA, KATIA M.; DELOLO, FABIO G.; ALVAREZ, ANISLAY; MOCELO, RAUL; PLUTIN, ANA M.; COMINETTI, MARCIA R.; CASTELLANO, EDUARDO E.; BATISTA, ALZIR A. Ru(II)-based complexes with N-(acyl)-N `,N `-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells. Journal of Inorganic Biochemistry, v. 150, p. 63-71, SEP 2015. Web of Science Citations: 44.
BARBOSA, MARILIA I. F.; CORREA, RODRIGO S.; POZZI, LUCAS V.; LOPES, ERICA DE O.; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; ELLENA, JAVIER; MACHADO, SERGIO DE P.; VON POELHSITZ, GUSTAVO; BATISTA, ALZIR A. Ruthenium(II) complexes with hydroxypyridinecarboxylates: Screening potential metallodrugs against Mycobacterium tuberculosis. Polyhedron, v. 85, p. 376-382, JAN 8 2015. Web of Science Citations: 17.
RODRIGUES, M. V. N.; CORREA, R. S.; VANZOLINI, K. L.; SANTOS, D. S.; BATISTA, A. A.; CASS, Q. B. Characterization and screening of tight binding inhibitors of xanthine oxidase: an on-flow assay. RSC ADVANCES, v. 5, n. 47, p. 37533-37538, 2015. Web of Science Citations: 6.
MARTINS, FELIPE TERRA; CORREA, RODRIGO S.; BATISTA, ALZIR AZEVEDO; ELLENA, JAVIER. Quasi-enantiomeric single-nucleoside and quasi-racemic two-nucleoside hydrochloride salts and ruthenium complexes of cytidine and 2 `,3 `-dideoxycytidine analogs unveiling the negligible structure-driving role of the 2 `,3 `-moieties. CrystEngComm, v. 16, n. 30, p. 7013-7022, 2014. Web of Science Citations: 9.

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