Effect of coordinated ligands on antiproliferative activity and DNA cleavage property of three mononuclear Cu(II)-terpyridine complexes

• Published in: European journal of medicinal chemistry Vol. 57; pp. 449 - 458
• Main Authors: Manikandamathavan, Verasuntharam M., Rajapandian, Varatharaj, Freddy, Allen J., Weyhermüller, Thomas, Subramanian, Venkatesan, Nair, Balachandran Unni
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01.11.2012; Elsevier
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma of Lung; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Binding Sites; Biological and medical sciences; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Copper - chemistry; Copper(II) complex; Crystallography, X-Ray; Cytotoxicity; Deoxyribonucleases - chemistry; Deoxyribonucleases - metabolism; DNA - chemistry; DNA - metabolism; DNA Cleavage; DNA, Superhelical - chemistry; DNA, Superhelical - metabolism; Effect of ligands; Electron Spin Resonance Spectroscopy; Humans; Hydrogen Peroxide - metabolism; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Mass Spectrometry; Medical sciences; Miscellaneous; Molecular Docking Simulation; Pharmacology. Drug treatments; Plasmids; Pyridines - chemistry; Terpyridine; Copper(II) complex; Effect of ligands; NASWQUNGDPOJLE-UHFFFAOYSA-N; FQCGEXJVPDGITJ-UHFFFAOYSA-L; Cytotoxicity; Terpyridine; Apoptosis; KITSDJCUXVEESL-UHFFFAOYSA-L
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.06.039

Three mononuclear copper(II) complexes, [Cu(tpy)Cl2] 1, [Cu(tpy)(NO3)2(H2O)] 2 and [Cu(Ptpy)Cl2]·H2O·HCl 3 have been synthesised and characterized by various spectroscopic techniques and single crystal X-ray diffraction. Complexes 1 and 3 have five coordinate geometry in solid state, whereas complex 2 has six coordinate geometry. Mass spectral and EPR evidence suggest that in solution all the three complexes exist predominantly as a four coordinate species. Molecular modelling and DNA cleavage studies indicate that complexes 1 and 2 are DNA minor groove binders, whereas 3 is an intercalator. All the three complexes show nuclease activity in the presence of hydrogen peroxide. The three complexes have been found to be cytotoxic towards A549 lung adenocarcinoma cells. [Display omitted] ► Three new mononuclear Cu (II) terpyridine complexes have been synthesised and crystallographically characterised. ► These complexes have been found to be cytotoxic to cancerous cell line. ► The observed cytotoxicity of the complexes has been found to be due to their ability to bring about apoptotic cell death. ► These compounds may have potential application in chemotherapy.