Influence of carboxylic acid functionalities in ruthenium (II) polypyridyl complexes on DNA binding, cytotoxicity and antioxidant activity: Synthesis, structure and in vitro anticancer activity

• Published in: European journal of medicinal chemistry 2013-01, Vol.59, p.253-264
• Main Authors: Sathiya Kamatchi, Thangavel, Chitrapriya, Nataraj, Kim, Seog K., Fronczek, Frank R., Natarajan, Karuppannan
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidant activity; Antioxidants - chemistry; Bipyridine; Carboxylic Acids - chemistry; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Crystallography, X-Ray; Cytotoxicity; Dicarboxylic acid; DNA - chemistry; DNA interaction; Humans; Inhibitory Concentration 50; Models, Molecular; Molecular Structure; Protein Binding - drug effects; Pyridines - chemistry; Ruthenium; Ruthenium - chemistry
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.11.024

Four new Ru(II) complexes [RuHCl(bpy)(PPh3)(CO)] (1), [RuHCl(bpy)(AsPh3)(CO)] (2) (bpy = 2,2′-bipyridine), [RuCl(HL)(PPh3)2(CO)] (3) and [RuCl(HL)(AsPh3)2(CO)] (4) (HL = 2,2′-bipyridine-4,4′-dicarboxylic acid) were synthesized and characterized. X-ray diffraction was used to characterize 3 in solid state. The interactions of these complexes with DNA were explored by different techniques which revealed that the complexes could bind to CT-DNA through non-intercalation. The in vitro cytotoxic and antioxidant activities of the complexes validated against a panel of cancer cell lines and free radicals showed that 3 and 4 possess quite high anticancer and antioxidant activities over 1, 2 and standard drugs. An apparent dependence of biological activities on incorporation of COOH in bipyridine moiety was noticed: Inclusion of COOH caused significant differences in DNA binding, cytotoxicity and antioxidant activity. [Display omitted] The impact of COOH on various biological activities revealed that complexes which do not contain COOH showed good DNA binding and complexes which contain COOH behaved as excellent antitumor agents/antioxidants. ► Four new ruthenium(II) complexes have been synthesized and characterized. ► The impact of COOH on various biological activities have been investigated. ► The DNA interactions of these complexes were studied by a variety of techniques. ► The cytotoxic activity was evaluated against a panel of cancer cell lines. ► The antioxidant activity against various radicals have also been examined.