Evaluation of anticancer properties of ruthenium(II)complexes containing lapachol and lawsone bioligands

• Grant number: 14/04147-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2014
• End date: June 30, 2018
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alzir Azevedo Batista
• Grantee: Katia Mara de Oliveira
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 16/18530-4 - Evaluation of the mechanism of action of ruthenium complexes containing bioactive natural products, BE.EP.DR

Abstract

The present project centers on the synthesis of complexes of ruthenium (II) containing lapachol and lawsone bioligands, which may present the following formulas: [Ru(L-L)(bipy)(dppf)]PF6, [Ru(L-L)(bipy)(dppe)]PF6 and [Ru(L-L)(dppe)2]PF6, where L-L = lapachol and lawsone, bipy = 2,2'-bipyridine, dppf = 1,1'-bis(diphenylphosphino)ferrocene and dppe = 1,2'-bis (diphenylphosphino)ethane. The complexes obtained will be evaluated for their cytotoxic activity in cell lines of breast cancer (MCF-7), prostate (DU-145), lung (A549), normal mouse fibroblasts (L929) and human (FH), and those that perform best will be submitted to further studies seeking determine the mechanism of action of the same. Initially the interaction of the complexes with DNA and BSA will be evaluated. Subsequently will be analyzed membrane integrity, mitochondrial depolarization, cell cycle, apoptosis assay by annexin V, caspase activity quantification and reactive oxygen species, and determination of apoptosis-related proteins by the technique of Western blotting. Eventually, by means of chemical and biological data, the aim is verify whether there is any correlation between structure and activity, as well as a possible mechanism of action. Similar to the above-mentioned compounds with general formulas [Ru(L-L)(dppb)(N-N)]PF6 and [Ru(lawsone)(PPh3)2(N-N)]PF6 (where dppb = 1,4-bis (diphenylphosphino)butane, PPh3 = triphenylphosphine and NN = 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine or 1,10-phenanthroline) obtained, characterized and tested against MCF-7 cell line in the master the candidate may also be used in the development of this project. (AU)

Scientific publications

(10)

(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.; 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. (14/04147-9, 13/26559-4)

OLIVEIRA, KATIA M.; LIANY, LUNA-DULCEY; CORREA, RODRIGO S.; DEFLON, VICTOR M.; COMINETTI, MARCIA R.; BATISTA, ALZIR A.. Selective Ru(II)/lawsone complexes inhibiting tumor cell growth by apoptosis. Journal of Inorganic Biochemistry, v. 176, p. 66-76, NOV 2017. (14/04147-9)

OLIVEIRA, KATIA M.; CORREA, RODRIGO S.; BARBOSA, MARILIA I. F.; ELLENA, JAVIER; COMINETTI, MARCIA R.; BATISTA, ALZIR A.. Ruthenium(II)/triphenylphosphine complexes: An effective way to improve the cytotoxicity Of lapachol. Polyhedron, v. 130, p. 108-114, JUL 7 2017. (14/04147-9)

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)

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)

TEIXEIRA, THALLITA MONTEIRO; ARRAES, ISABELA GASPARINI; ABREU, DAVI CARVALHO; OLIVEIRA, KATIA M.; CORREA, RODRIGO S.; BATISTA, ALZIR A.; BRAUNBECK, THOMAS; SILVEIRA LACERDA, ELISAANGELA DE PAULA. Ruthenium complexes show promise when submitted to toxicological safety tests using alternative methodologies. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 216, APR 15 2021. (14/04147-9)

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. 9-pg., 2019-12-01. (13/26559-4, 14/04147-9)

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. 9-pg., 2015-09-01. (13/26559-4, 14/04147-9)

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. (14/04147-9, 13/26559-4)

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)