Evaluation of catacholase mimicking activity and apoptosis in human colorectal carcinoma cell line by activating mitochondrial pathway of copper(II) complex coupled with 2-(quinolin-8-yloxy)(methyl)benzonitrile and 8-hydroxyquinoline.
To evaluate the cytotoxic potential of metal-based chemotherapeutic candidate towards the colorectal cancer, we have synthesized a new copper(II) complex [Cu(qmbn)(q)(Cl)] (1) (where, qmbn = 2-(quinolin-8-yloxy)(methyl)benzonitrile and q = 8-hydroxyquinoline) and structurally characterized by single crystal X-ray, Powder-XRD, FTIR and thermogravimetric analysis (TGA). The structural analysis reveals that copper(II) ions exist in a distorted square pyramidal (τ = ~0.1), with ligation of a chloride ion, oxygen atom and two nitrogen atoms at equatorial position and one oxygen atom at apical position. The cytotoxicity potential of complex 1 was executed against human colorectal cell lines (HCT116), which showed that 1 induces mitochondrion-mediated apoptotic cell death via activation of the Bax (pro-apoptotic protein) caspases-3 and 9 proteins. Interestingly, complex 1 was found to be a good candidate as electron-transfer catalyst which mimics catacholase with high turnover frequency (kcat = 1.03 × 102 h-1) for the conversion of the model substrate 3,5-di-tertbutylcatechol (3,5-DTBC) to 3,5-di-tertbutylquinone (3,5-DTBQ). Furthermore, molecular docking studies revealed that complex 1 was successfully localized inside the binding pocket of protein kinase (Akt), which validate the mechanism and mode of interaction of 1 that displayed cytotoxic activity experimentally. The obtained outcomes reveal that the complex 1 could be utilized as an encouraging perspective in the development of new therapeutic candidate for colon cancer.
['Ali|Arif|A|', 'Mishra|Snehasis|S|', 'Kamaal|Saima|S|', 'Alarifi|Abdullah|A|', 'Afzal|Mohd|M|', 'Saha|Krishna Das|KD|', 'Ahmad|Musheer|M|']
D000970:Antineoplastic Agents D017209:Apoptosis D049109:Cell Proliferation D002800:Cholinesterase Inhibitors D002802:Cholinesterases D056831:Coordination Complexes D003300:Copper D004305:Dose-Response Relationship, Drug D004354:Drug Screening Assays, Antitumor D045325:HCT116 Cells D006801:Humans D008928:Mitochondria D062105:Molecular Docking Simulation D015394:Molecular Structure D013329:Structure-Activity Relationship D014407:Tumor Cells, Cultured
Mitochondrial pathway Copper(II) complex Single crystal Molecular docking MTT assay