CYTOTOXICITY AND MECHANISM OF ACTION OF RUTHENIUM COMPLEXES CONTAINING NATURAL PRODUCTS OR DERIVATIVES

• Grant number: 16/16312-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2016
• End date: October 31, 2018
• 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

The present project aims the syntheses of four series of ruthenium complexes containing diphosphines and diimines, as well natural products or derivatives as ligands.Series 1: Compounds with general formula [Ru(O-O)(dppb)(bipy)]PF6, where O-O = galic acid, cinamic acid, salicilic acid or 4-aminosalicilic acid and derivatives;Série 2: Compounds with general formula [Ru(O-O)(P-P)2]PF6 (P-P = dppm, 1,1-bis(difenylphosphine)methane; dppe, 1,2-bis(difenylphosphine)ethane e dppp = 1,3-bis(difenylphosphine)propane);Série 3: Compounds with general formula [Ru(L)(dppb)(N-N)]PF6 (N-N = 2,2`-bipyridine, 4,4`-dimetil 2,2'-bipyridine e 1,10-phenantroline; L = lapachol or lausone;Série 4: Compounds of type [Ru(O-O)(·6-p-cimene)(PPh3)]Cl.The compounds will be characterized by several techniques, such as elemental analysis (C, N, H), IR and UV/Vis spectroscopies; RMN (1H, 13C e 31P), electrochemistry (cyclic voltammetry and pulse differential voltammetry) and X-ray diffraction.Test, aiming the evaluation of the cytotoxicity of the compounds, against tumor cells will be realized. Also, experiments to verify the possible activity of the compounds against Chagas disease and Mycobacterius tuberculosis will be promoted. The ability of the complexes as antioxidant agents also will be realized.Study on the possible mechanism of action of the complexes, against the above diseases will be promoted. (AU)

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)

MUNDIM GUEDES, ADRIANA PEREIRA; MELLO-ANDRADE, FRANCYELLI; PIRES, WANESSA CARVALHO; MONTES DE SOUSA, MARIA ALICE; FAUSTINO DA SILVA, PAULA FRANCINETE; DE CAMARGO, MARIANA S.; GEMEINER, HENDRYK; AMAURI, MENEGARIO A.; CARDOSO, CLEVER GOMES; DE MELO REIS, PAULO ROBERTO; et al. Heterobimetallic Ru(ii)/Fe(ii) complexes as potent anticancer agents against breast cancer cells, inducing apoptosis through multiple targets. METALLOMICS, v. 12, n. 4, p. 547-561, APR 1 2020. (16/16312-0)

OLIVEIRA, KATIA M.; HONORATO, JOAO; DEMIDOFF, FELIPE C.; SCHULTZ, MARIO S.; NETTO, CHAQUIP D.; COMINETTI, MARCIA R.; CORREA, RODRIGO S.; BATISTA, ALZIR A.. Lapachol in the Design of a New Ruthenium(II)-Diphosphine Complex as a Promising Anticancer Metallodrug. Journal of Inorganic Biochemistry, v. 214, JAN 2021. (16/16312-0, 14/04147-9)

LEITE, TAISE H. O.; GRAWE, GREGORY; HONORATO, JOAO; CUNHA, BEATRIZ N.; NASCIMENTO, OTACIRO R.; DE VARGAS, PAMELA S.; DONATONI, CAROLINA; OLIYEIRA, KLEBER T.; LOPES, JEFFERSON M. S.; BARBOSA NETO, NEWTON M.; et al. Remarkable Electronic Effect on the meso-Tetra(thienyl)porphyrins. Inorganic Chemistry, v. 58, n. 2, p. 1030-1039, JAN 21 2019. (18/00106-7, 15/21110-4, 16/16312-0)

OLIVEIRA, KATIA M.; PETERSON, ERICA J.; CARROCCIA, MURILO C.; COMINETTI, MARCIA R.; DEFLON, VICTOR M.; FARRELL, NICHOLAS P.; BATISTA, ALZIR A.; CORREA, RODRIGO S.. Ru(II)-Naphthoquinone complexes with high selectivity for triple-negative breast cancer. DALTON TRANSACTIONS, v. 49, n. 45, p. 16193-16203, DEC 7 2020. (14/04147-9, 16/18530-4, 16/16312-0)

DA SILVA, MONIZE M.; DE CAMARGO, MARIANA S.; CORREA, RODRIGO S.; CASTELLI, SILVIA; DE GRANDIS, RONE A.; TAKARADA, JESSICA E.; VARANDA, ELIANA A.; CASTELLANO, EDUARDO E.; DEFLON, VICTOR M.; COMINETTI, MARCIA R.; et al. Non-mutagenic Ru(ii) complexes: cytotoxicity, topoisomerase IB inhibition, DNA and HSA binding. DALTON TRANSACTIONS, v. 48, n. 39, p. 14885-14897, OCT 21 2019. (16/16312-0)

GRAMINHA, ANGELICA E.; HONORATO, JOAO; DULCEY, LIANY LUNA; GODOY, LUANI REZENDE; BARBOSA, MARILIA F.; COMINETTI, MARCIA R.; MENEZES, ANTONIO C.; BATISTA, ALZIR A.. Evaluation of the biological potential of ruthenium(II) complexes with cinnamic acid. Journal of Inorganic Biochemistry, v. 206, MAY 2020. (14/19632-0, 15/24940-8, 16/16312-0)

VELOZO-SA, VIVIANNE S.; PEREIRA, LUCIANO R.; LIMA, ALINY P.; MELLO-ANDRADE, FRANCYELLI; REZENDE, MANUELA R. M.; GOVEIA, REBECA M.; PIRES, WANESSA C.; SILVA, MONIZE M.; OLIVEIRA, KATIA M.; FERREIRA, ANTONIO G.; et al. In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes. DALTON TRANSACTIONS, v. 48, n. 18, p. 6026-6039, MAY 14 2019. (14/04147-9, 16/16312-0)

NAVES, MARINA A.; GRAMINHA, ANGELICA E.; VEGAS, LEGNA C.; LUNA-DULCEY, LIANY; HONORATO, JOAO; MENEZES, ANTONIO C. S.; BATISTA, ALZIR A.; COMINETTI, MARCIA R.. Transport of the Ruthenium Complex [Ru(GA)(dppe)(2)]PF6 into Triple-Negative Breast Cancer Cells Is Facilitated by Transferrin Receptors. MOLECULAR PHARMACEUTICS, v. 16, n. 3, p. 1167-1183, MAR 2019. (16/16312-0, 15/24940-8, 13/00798-2)

DE GRANDIS, RONE APARECIDO; DA SILVA DOS SANTOS, PATRICK WELLINGTON; DE OLIVEIRA, KATIA MARA; TOMAZELA MACHADO, ANA RITA; AISSA, ALEXANDRE FERRO; BATISTA, ALZIR AZEVEDO; GREGGI ANTUNES, LUSANIA MARIA; PAVAN, FERNANDO ROGERIO. Novel lawsone-containing ruthenium(II) complexes: Synthesis, characterization and anticancer activity on 2D and 3D spheroid models of prostate cancer cells. BIOORGANIC CHEMISTRY, v. 85, p. 455-468, APR 2019. (18/00163-0, 16/22429-7, 16/16312-0)

GRAMINHA, ANGELICA E.; HONORATO, JOAO; CORREA, RODRIGO S.; COMINETTI, MARCIA R.; MENEZES, ANTONIO C. S.; BATISTA, ALZIR A.. A novel ruthenium(II) gallic acid complex disrupts the actin cytoskeleton and inhibits migration, invasion and adhesion of triple negative breast tumor cells. DALTON TRANSACTIONS, v. 50, n. 1, p. 323-335, JAN 7 2021. (14/19632-0, 16/16312-0, 15/24940-8, 13/07600-3)

DE CAMARGO, MARIANA S.; DE GRANDIS, RONE A.; DA SILVA, MONIZE M.; DA SILVA, PATRICIA B.; SANTONI, MARIANA M.; EISMANN, CARLOS E.; MENEGARIO, AMAURI A.; COMINETTI, MARCIA R.; ZANELLI, CLESLEI F.; PAVAN, FERNANDO R.; et al. Determination of in vitro absorption in Caco-2 monolayers of anticancer Ru(II)-based complexes acting as dual human topoisomerase and PARP inhibitors. BIOMETALS, v. 32, n. 1, p. 89-100, FEB 2019. (12/21529-7, 16/22429-7, 16/16312-0)

RIBEIRO, GABRIEL H.; GUEDES, ADRIANA P. M.; DE OLIVEIRA, TAMIRES D.; DE CORREIA, CAMILA R. S. T. B.; COLINA-VEGAS, LEGNA; LIMA, MAURO A.; NOBREGA, JOAQUIM A.; COMINETTI, MARCIA R.; ROCHA, V, FILLIPE; FERREIRA, ANTONIO G.; et al. Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction. Inorganic Chemistry, v. 59, n. 20, p. 15004-15018, OCT 19 2020. (16/16312-0, 16/23130-5)