DNA-Binding and Cytotoxicity of Copper(I) Complexes Containing Functionalized Dipyridylphenazine Ligands

Abstract

A set of copper(I) coordination compounds with general formula [CuBr(PPh3)(dppz-R)] (dppz-R = dipyrido[3,2-a:2’,3’-c]phenazine (Cu-1), 11-nitrodipyrido[3,2-a:2’,3’-c]phenazine (Cu-2), 11-cyanodipyrido[3,2-a:2’,3’-c]phenazine (Cu-3), dipyrido[3,2-a:2’,3’-c]phenazine-11-phenone (Cu-4), 11,12-dimethyldipyrido[3,2-a:2’,3’-c]phenazine (Cu-5)) have been prepared and characterized by elemental analysis, 1H-NMR and 31P-NMR spectroscopies as well as mass spectrometry. The structure of Cu-1 was confirmed by X-ray crystallography. The effect of incorporating different functional groups on the dppz ligand on the binding into CT-DNA was evaluated by absorption spectroscopy, fluorescence quenching of EtBr-DNA adducts, and viscosity measurements. The functional groups affected the binding modes and hence the strength of binding affinities, as suggested by the changes in the relative viscosity. The differences in the quenching constants (Ksv) obtained from the fluorescence quenching assay highlight the importance of the functional groups in altering the binding sites on the DNA. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA changing with the different functional groups. Evaluation of the anticancer activities of the five copper compounds against two different cancer cell lines (M-14 and MCF-7) indicated the importance of the functional groups on the dppz ligand on the anticancer activities. Among the five copper complexes, the cyano-containing complex (Cu-3) has the best anticancer activities.

Synthesis, Structural Studies, and Anticancer Properties of [CuBr(PPh3)2(4,6-Dimethyl-2-Thiopyrimidine-κS]

“…In our group, [CuBr(1,10-phenanthroline)(PPh 3 )] was screened in vivo against four cancer cell lines and presented cytotoxic effects comparable to cisplatin against MFC-7 and PC3 cancer cell lines [25]. Changing the diimine ligands alters the anticancer properties; optimum cytotoxicity against several cancer cell lines were detected with dipyrido[3,2-a:2 ,3c]phenazine (dppz) ligand and its derivatives [26,27]. However, the thione-containing complexes have received far less attention [28][29][30].…”

Tuning anticancer properties and DNA-binding of Pt(ii) complexes via alteration of nitrogen softness/basicity of tridentate ligands

“…The specific viscosity η and η 0 were derived from the formulation [( t − t b )/ t b ] where t is the observed flow time and t b is the buffer flow time. 28,29,33…”

Tuning the anticancer properties of Pt(ii) complexes via structurally flexible N-(2-picolyl)salicylimine ligands

“…The specic viscosities h and h 0 were calculated using the formulation [(t − t b )/t b ] where t is the observed ow time and t b is the buffer ow time. 31,32,35 Computational studies…”