Anomalous behavior of pentacoordinate copper complexes of dimethylphenanthroline and derivatives of terpyridine ligands: Studies on DNA binding, cleavage and apoptotic activity

• Published in: European journal of medicinal chemistry 2011-02, Vol.46 (2), p.608-617
• Main Authors: Rajalakshmi, Subramaniyam, Weyhermüller, Thomas, Freddy, Allen J., Vasanthi, Hannah R., Nair, Balachandran Unni
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Binding Sites - drug effects; Biological and medical sciences; Cattle; Cell Line, Tumor; Copper - chemistry; Copper complexes; Crystallography, X-Ray; Cytotoxicity; DNA - chemistry; DNA - drug effects; DNA binding; DNA cleavage; DNA Cleavage - drug effects; Drug Screening Assays, Antitumor; General aspects; Groove binder; Humans; Ligands; Medical sciences; Models, Molecular; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Pharmacology. Drug treatments; Phenanthrolines - chemistry; Pyridines - chemistry; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.11.041

Copper(II) complexes with substituted terpyridine ligands, namely [Cu(itpy)(dmp)](NO 3) 2 ( 1) and [Cu(ptpy)(dmp)](NO 3) 2 ( 2) have been synthesized and characterized. The interaction of the complexes with CT-DNA has been explored using spectroscopic techniques and viscosity. Complexes 1 and 2 bind in the grooves of DNA, interestingly 1 in the minor and 2 in the major groove. Both the complexes have been found to promote DNA cleavage; complex 1 through hydrolytic and 2 oxidative. Complexes 1 and 2 have been found to be cytotoxic and bring about apoptosis of human lung cancer cell line A549. [Display omitted] ► Synthesis of two pentacoordinate Copper(II) complexes and characterization by X-Ray crystal diffraction. ► Both the complexes are avid DNA binders. ► Complex 1 binds in the minor groove whereas complex 2 binds in the major groove of DNA. ► Complex 1 cleaves DNA hydrolytically whereas complex 2 cleaves in the presence of hydrogen peroxide. ► Both the complexes bring about apoptosis of A549 lung cancer cell line.