Search for ruthenium (II) complexes, with chemotherapeutic properties: evaluation of possible sinergistic effects and possible action mechanism

• Grant number: 14/10516-7
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2014
• End date: February 28, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Alzir Azevedo Batista
• Grantee: Alzir Azevedo Batista
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

In this work we intend to synthesize complexes of general formula: [Ru(N-S)(bipy)(P-P)]PF6, [Ru(N-S)2(PPh3)2], [Ru(N-S)(fen)(P-P)]PF6 e [Ru(N-S)2(P-P)]; where (N-S = 2-mercaptotiozoline, 4,6-diamino-2-mercaptopirimidine, 2-mercaptoimadozol, 2-mercapto-1-metilimidazol, 6-mercaptopiridine-3-carboxílic acid; P-P = dppm = 1,1`-bis(diphenylphosphine)methane, dppe = 1,2-bis(diphenylphosphine)ethane, dppp = 1,3-bis(diphenylphosphine)propane, dppb = 1,4-bis(diphenylphosphine)butane and PPh3 (triphenylphosphine); bipy= 2,2'-bipyridine). The complexes will be characterized by 31P{1H} NMR, IR, UV-Vis spectroscopy, molar conductivity, elemental analysis, cyclic and differential pulse voltammetry and X-ray diffractometry (when it will be possible to obtain monocrystals). After the synthesis of complexes with high purity their cytotoxic activities will be assessed against breast (MDA-MB-231) and prostate (DU 145) tumor cells, by colorimetric MTT method, which will be related to healthy cells (L-929, mouse). After this screening those complexes that should show more promising results will be assessed with respect their possible mechanism of action, such as: capacity to cause demage to the DNA ( Cytoma assess, DNA fragmentation), chance in the cellular cyclic and induction to apoptose in tumor cells (Flux Cytometry).Also, the interaction of the complexes with DNA will be studied, by spectrophotometric titulation (UV/Vis) and viscosity experiments of DNA, and spectrofluorimetric experiments with HSA (human seric albumin). In the end of the work there is an expectation that the chemical and biological data should be related with respect structure and activity of the complex on study. (AU)

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)

MACEDO, TAIS S.; COLINA-VEGAS, LEGNA; DA PAIXAO, MARCELO; NAVARRO, MARIBEL; BARRETO, BRENO C.; OLIVEIRA, POLIANA C. M.; MACAMBIRA, SIMONE G.; MACHADO, MARTA; PRUDENCIO, MIGUEL; D'ALESSANDRO, SARAH; et al. Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents. Parasitology, v. 143, n. 12, p. 1543-1556, OCT 2016. (14/10516-7)

DE CAMARGO, MARIANA S.; DA SILVA, MONIZE M.; CORREA, RODRIGO S.; VIEIRA, SARA D.; CASTELLI, SILVIA; D'ANESSA, ILDA; DE GRANDIS, RONE; VARANDA, ELIANA; DEFLON, VICTOR M.; DESIDERI, ALESSANDRO; et al. Inhibition of human DNA topoisomerase IB by nonmutagenic ruthenium( II)-based compounds with antitumoral activity. METALLOMICS, v. 8, n. 2, p. 179-192, 2016. (14/10516-7, 12/21529-7, 13/20078-4)

TAKARADA, JESSICA E.; GUEDES, ADRIANA P. M.; CORREA, RODRIGO S.; SILVEIRA-LACERDA, ELISANGELA DE P.; CASTELLI, SILVIA; IACOVELLI, FEDERICO; DEFLON, VICTOR MARCELO; BATISTA, ALZIR AZEVEDO; DESIDERI, ALESSANDRO. Ru/Fe bimetallic complexes: Synthesis, characterization, cytotoxicity and study of their interactions with DNA/HSA and human topoisomerase IB. Archives of Biochemistry and Biophysics, v. 636, p. 28-41, DEC 15 2017. (14/10516-7)

ANA M. PLUTÍN; ANISLAY ALVAREZ; RAÚL MOCELO; RAÚL RAMOS; OSMAR C. SÁNCHEZ; EDUARDO E. CASTELLANO; MONIZE M. DA SILVA; WILMER VILLARREAL; LEGNA COLINA-VEGAS; FERNANDO R. PAVAN; et al. Structure/Activity of PtII/N,N-Disubstituted-N'-acylthiourea Complexes: Anti-Tumor and Anti-Mycobacterium tuberculosis Activities. Journal of the Brazilian Chemical Society, v. 29, n. 6, p. 1256-1267, 2018-06-00. (14/10516-7)

MELLO-ANDRADE, FRANCYELLI; CARDOSO, CLEVER GOMES; RIBEIRO E SILVA, CAROLINA; CHEN-CHEN, LEE; DE MELO-REIS, PAULO ROBERTO; DE LIMA, ALINY PEREIRA; OLIVEIRA, RHAUL; MACHADO FERRAZ, IRVIN BRYAN; GRISOLIA, CESAR KOPPE; PINHEIRO ALMEIDA, MARCIO AURELIO; et al. Acute toxic effects of ruthenium (II)/amino acid/diphosphine complexes on Swiss mice and zebrafish embryos. BIOMEDICINE & PHARMACOTHERAPY, v. 107, p. 1082-1092, NOV 2018. (14/10516-7)

PIRES, WANESSA CARVALHO; VIEIRA LIMA, BENEDICTO AUGUSTO; PEREIRA, FLAVIA DE CASTRO; LIMA, ALINY PEREIRA; MELLO-ANDRADE, FRANCYELLI; SILVA, HUGO DELLEON; DA SILVA, MONIZE MARTINS; COLINA-VEGAS, LEGNA; ELLENA, JAVIER; BATISTA, ALZIR A.; et al. Ru(II)/diphenylphosphine/pyridine-6-thiolate complexes induce S-180 cell apoptosis through intrinsic mitochondrial pathway involving inhibition of Bcl-2 and p53/Bax activation. Molecular and Cellular Biochemistry, v. 438, n. 1-2, p. 199-217, JAN 2018. (14/10516-7)

BARBOSA, M. I. F.; CORREA, R. S.; BASTOS, T. M.; POZZI, L. V.; MOREIRA, D. R. M.; ELLENA, J.; DORIGUETTO, A. C.; SILVEIRA, R. G.; OLIVEIRA, C. R.; KUZNETSOV, A. E.; et al. Structural isomerism of Ru(II)-carbonyl complexes: synthesis, characterization and their antitrypanosomal activities. NEW JOURNAL OF CHEMISTRY, v. 41, n. 11, p. 4468-4477, JUN 7 2017. (14/10516-7)

MACEDO, TAIS S.; VILLARREAL, WILMER; COUTO, CAMILA C.; MOREIRA, DIOGO R. M.; NAVARRO, MARIBEL; MACHADO, MARTA; PRUDENCIO, MIGUEL; BATISTA, ALZIR A.; SOARES, MILENA B. P.. Platinum(II)-chloroquine complexes are antimalarial agents against blood and liver stages by impairing mitochondrial function. METALLOMICS, v. 9, n. 11, p. 1548-1561, NOV 1 2017. (14/10516-7)

PLUTIN, ANA M.; ALVAREZ, ANISLAY; MOCELO, RAUL; RAMOS, RAUL; SANCHEZ, OSMAR C.; CASTELLANO, EDUARDO E.; DA SILVA, MONIZE M.; VILLARREAL, WILMER; COLINA-VEGAS, LEGNA; PAVAN, FERNANDO R.; et al. Structure/Activity of Pt-II/& IT;N & IT;,& IT;N & IT;-Disubstituted-& IT;N & IT;'-acylthiourea Complexes: Anti-Tumor and Anti-& IT;Mycobacterium tuberculosis & IT; Activities. Journal of the Brazilian Chemical Society, v. 29, n. 6, p. 1256-1267, JUN 2018. (14/10516-7)