A comparative study of novel ruthenium(III) and iron(III) complexes containing uracil; docking and biological studies.

Structural and biological studies were conducted on the novel complexes [Fe(U)2(H2O)2]Cl3 (FeU) and [Ru(U)2(H2O)2]Cl3 (RuU) (U = 5,6-Diamino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) to develop an anticancer drug candidate. The two complexes have been synthesized and characterized. Based on our findings, these complexes have octahedral geometry. The DNA-binding study proved that both complexes coordinated with CT-DNA. The docking study confirmed the potency of both complexes in downregulating the topoisomerase I protein through their high binding affinity. Biological studies have established that both complexes can act as potent anticancer agents against three cancer cell lines. RuU or FeU complexes induce apoptosis in breast cancer cells by increasing caspase9 protein and inhibiting proliferating cell nuclear antigen (PCNA) activity. In addition, both complexes down-regulate topoisomerase I expression in breast cancer cells. Therefore, the RuU and FeU complexes' anticancer activities were mediated via both apoptosis induction and topoisomerase I down-regulation. In conclusion, both complexes have dual anticancer activity pathways that may be responsible for the selective cytotoxicity of the complexes. This makes them more suitable for the development of novel cancer treatment strategies.

Tuning the structural and catalytic properties of copper(II)-based complexes containing pyridine-2,6-diimines.

Four mononuclear penta coordinated copper(II) chelates, [CuLnBr2] nH2O, containing the tridentate neutral ligands, pyridine-2,6-diimine (Ln), were prepared via the template technique. Analytical and several physicochemical methods have been used to characterize the prepared metal chelates. Square-pyramidal stereochemistry was described to the current copper(II) complexes. DFT technique has been applied to optimize the structure of the running diimines and their corresponding copper-based compounds. Ligand substitution study performed to link the catalytic potency of the candidate oxidase mimics and their lability characters. Spectral investigations reveal that nature of substituents of the chelated ligands effectively tuning the Lewis acidity of copper(II) centers. Biomimetics of redox proteins specifically containing copper were examined towards the aerobic oxidation of polyphenol. Kinetic studies with the stopped-follow technique showed a close association between the Lewis acidity of the copper(II) nuclei of the prepared chelates and their oxidase-like activity. The catalytic activity of the natural enzyme (catechol oxidase from sweet potatoes) measured and compared with that for the present CuII chelates. The thermodynamic parameter drive force (ΔG° or λ) of the performed oxidation processes was determined from the values of redox potential of the chemical species involved in these catalytic reactions. The proposed catalytic reactions pathways have been discussed based on the outcomes of the kinetic investigations.Communicated by Ramaswamy H. Sarma.