Naphthoyl benzhydrazine-decorated binuclear arene Ru() complexes as anticancer agents targeting human breast cancer cells

Breast cancer is the most dangerous type in women and its fatality rate has increased over the past decade. To develop more potent and target-specific breast cancer drugs, six arene ruthenium( ii ) complexes ( 1-6 ) containing naphthoyl benzhydrazine ligands (NL1-NL3) were synthesized and characteri...

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Bibliographic Details
Published in:Dalton transactions : an international journal of inorganic chemistry 2023-11, Vol.52 (44), p.16376-16387
Main Authors: Abirami, Arunachalam, Devan, Umapathy, Ramesh, Rengan, Antony Joseph Velanganni, Arockiam, Grzegorz Ma ecki, Jan
Format: Article
Language:English
Subjects:
Anticancer properties
Apoptosis
Assaying
Breast cancer
Cell death
Electrons
Flow cytometry
Infrared analysis
Infrared spectroscopy
Ligands
NMR
Nuclear magnetic resonance
Ruthenium compounds
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Summary:Breast cancer is the most dangerous type in women and its fatality rate has increased over the past decade. To develop more potent and target-specific breast cancer drugs, six arene ruthenium( ii ) complexes ( 1-6 ) containing naphthoyl benzhydrazine ligands (NL1-NL3) were synthesized and characterized by analytical and spectroscopic (infrared, UV-visible, NMR and HR-MS) methods. The SC-XRD analysis of 1 and 6 demonstrates the bis N^O bidentate binding nature of ligands to ruthenium ions and a pseudo-octahedral geometry around the Ru( ii ) ion. Solution stability studies using UV-Vis spectroscopy evidenced the instantaneous hydrolysis of the complexes to form monoaquated species in a solution of 1 : 9 (v/v) DMSO/phosphate buffer. All the complexes were screened for their in vitro antiproliferative activities against different human breast cancer cells, including MCF-7, SkBr3, MDA-MB-468, MDA-MB-231, and non-cancerous HEK-293 cells, by an MTT assay, and they displayed good cancer cell growth inhibitory capacity with low IC 50 values. Notably, complexes 2 and 5 comprising methoxy and p -cymene groups exhibited excellent cytotoxicity towards SkBr3 cells compared to clinical drug cisplatin. AO-EB and HOECHST-33342 staining assays revealed apoptotic morphological changes in complex-treated cancer cells. Further, reactive oxygen species and mitochondrial membrane potential assays validated that the complexes induce apoptotic cell death via an intrinsic mitochondrial pathway with ROS production. In addition, the apoptotic induction and the quantification of late apoptosis were established with the aid of western blot and flow cytometry analysis, respectively. An array of arene binuclear ruthenium( ii ) benzhydrazine complexes were constructed to demonstrate their cytotoxicity against different human breast cancer cells. Various biochemical assays established that the complexes induce apoptosis mechanism.
ISSN:1477-9226
1477-9234
DOI:10.1039/d3dt02552g