Ru(ii)-Naphthoquinone complexes with high selectivity for triple-negative breast cancer
Author(s)
Oliveira, Katia M
Peterson, Erica J
Carroccia, Murilo C
Cominetti, Marcia R
Deflon, Victor M
Farrell, Nicholas P
Batista, Alzir A
Correa, Rodrigo S
Griffith University Author(s)
Year published
2020
Metadata
Show full item recordAbstract
Six new ruthenium(ii) complexes with lapachol (Lap) and lawsone (Law) with the general formula [Ru(L)(P-P)(bipy)]PF6, where L = Lap or Law, P-P = 1,2'-bis(diphenylphosphino)ethane (dppe), 1,4'-bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf) and bipy = 2,2'-bipyridine, were synthesized, fully characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis, IR spectroscopies and three of them by X-ray crystallography. All six complexes were active against breast (MCF-7 and MDA-MB-231) and prostate (DU-145) cancer cell lines with lower IC50 values than cisplatin. Complex ...
View more >Six new ruthenium(ii) complexes with lapachol (Lap) and lawsone (Law) with the general formula [Ru(L)(P-P)(bipy)]PF6, where L = Lap or Law, P-P = 1,2'-bis(diphenylphosphino)ethane (dppe), 1,4'-bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf) and bipy = 2,2'-bipyridine, were synthesized, fully characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis, IR spectroscopies and three of them by X-ray crystallography. All six complexes were active against breast (MCF-7 and MDA-MB-231) and prostate (DU-145) cancer cell lines with lower IC50 values than cisplatin. Complex [Ru(Lap)(dppe)(bipy)]PF6 (1a) showed significant selectivity for MDA-MB-231, a model of triple-negative breast cancer (TNBC), as compared to the "normal-like" human breast epithelial cell line, MCF-10A. Complex (1a) inhibited TNBC colony formation and induced loss of cellular adhesion. Furthermore, the complex (1a) induced mitochondrial dysfunction and generation of ROS, as is involved in the apoptotic cell death pathway. Preferential cellular uptake of complex (1a) was observed in MDA-MB-231 cells compared to MCF-10A cells, consistent with the observed selectivity for tumorigenic vs. non-tumorigenic cells. Taken together, these results indicate that ruthenium complexes containing lapachol and lawsone as ligands are promising candidates as chemotherapeutic agents.
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View more >Six new ruthenium(ii) complexes with lapachol (Lap) and lawsone (Law) with the general formula [Ru(L)(P-P)(bipy)]PF6, where L = Lap or Law, P-P = 1,2'-bis(diphenylphosphino)ethane (dppe), 1,4'-bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf) and bipy = 2,2'-bipyridine, were synthesized, fully characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis, IR spectroscopies and three of them by X-ray crystallography. All six complexes were active against breast (MCF-7 and MDA-MB-231) and prostate (DU-145) cancer cell lines with lower IC50 values than cisplatin. Complex [Ru(Lap)(dppe)(bipy)]PF6 (1a) showed significant selectivity for MDA-MB-231, a model of triple-negative breast cancer (TNBC), as compared to the "normal-like" human breast epithelial cell line, MCF-10A. Complex (1a) inhibited TNBC colony formation and induced loss of cellular adhesion. Furthermore, the complex (1a) induced mitochondrial dysfunction and generation of ROS, as is involved in the apoptotic cell death pathway. Preferential cellular uptake of complex (1a) was observed in MDA-MB-231 cells compared to MCF-10A cells, consistent with the observed selectivity for tumorigenic vs. non-tumorigenic cells. Taken together, these results indicate that ruthenium complexes containing lapachol and lawsone as ligands are promising candidates as chemotherapeutic agents.
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Journal Title
Dalton Transactions
Note
This publication has been entered in Griffith Research Online as an advanced online version.
Subject
Inorganic chemistry
Theoretical and computational chemistry
Other chemical sciences