title: Mixed ligand copper(II) complexes of 2,9-dimethyl-1,10-phenanthroline: tridentate 3N primary ligands determine DNA binding and cleavage and cytotoxicity.
abstract: A series of mononuclear mixed ligand copper(II) complexes of the type [Cu(L)(2,9-dmp)](ClO4)21-4, where L is a tridentate 3N ligand such as diethylenetriamine (L1) (1) or N-methyl-N'-(pyrid-2-yl-methyl)ethylenediamine (L2) (2) or di(2-picolyl)amine (L3) (3) or bis(pyrid-2-ylmethyl)-N-methylamine (L4) (4) and 2,9-dmp is 2,9-dimethyl-1,10-phenanthroline, has been isolated and characterized. The complexes 1 and 3 possess square-based pyramidal coordination geometry. Absorption spectral studies reveal that the intrinsic DNA binding affinity varies as 1>2>3>4. The higher DNA binding affinity of 1 arises from L1, which offers lower steric hindrance toward intercalation of 2,9-dmp co-ligand into DNA base pairs and is involved in hydrogen bonding interaction with DNA. Interestingly, all the complexes cleave pUC19 supercoiled DNA in the absence of an activating agent. They also exhibit oxidative (H2O2) DNA cleavage ability, which varies as 1>2>3>4, the highest cleavage efficiency of 1 being due to the largest amount of ROS it generates. The tryptophan emission-quenching experiment reveals that the stronger binding of 3 and 4 with bovine serum albumin (BSA) in the hydrophobic region, which is in line with DNA viscosity measurements. The IC50 values of 1-4 for MCF-7 breast cancer cell line are lower than that of cisplatin. Flow cytometry analysis reveals that 1 mediates the arrest of S and G2/M phases in the cell cycle progression at 24h harvesting time, which progresses into apoptosis. Hoechst 33258 staining studies indicate the higher potency of 1 to induce apoptosis.
authors.affiliation: Department of Chemistry, Central University of Tamil Nadu, Thiruvarur 610 004, India.
authors.forename: Mani
authors.initials: M
authors.lastname: Ganeshpandian
authors.affiliation: Department of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, India.
authors.forename: Sethu
authors.initials: S
authors.lastname: Ramakrishnan
authors.affiliation: Department of Chemistry, Central University of Tamil Nadu, Thiruvarur 610 004, India. Electronic address: palaniandavar@cutn.ac.in.
authors.forename: Mallayan
authors.initials: M
authors.lastname: Palaniandavar
authors.affiliation: Analytical Science Discipline, Central Salt and Marine Chemical Research Institute, Bhavnagar 364 002, India.
authors.forename: Eringathodi
authors.initials: E
authors.lastname: Suresh
authors.affiliation: Department of Animal Science, Bharathidasan University, Tiruchirappalli 620 024, India.
authors.forename: Anvarbatcha
authors.initials: A
authors.lastname: Riyasdeen
authors.affiliation: Mahatma Gandhi-Doerenkamp Center for Alternatives to use of Animals in Life Science Education, Bharathidasan University, Tiruchirappalli, 620 024, India; Visiting Scientist, Department of Food and Nutrition, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Mohammad Abdulkadher
authors.initials: MA
authors.lastname: Akbarsha
mesh_terms: D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D010618:Phenanthrolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D008024:Ligands; D010618:Phenanthrolines; D003300:Copper; C002701:neocuproine; D004247:DNA
keywords: 2,9-Dimethyl-1,10-phenanthroline; Cell cycle arrest; Hydrogen bonding potential; Hydrophobicity; Mixed ligand copper(II) complexes