DNA as a Target for Anticancer Phen-Imidazole Pd(II) Complexes.

Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of Pd(phen)(FIP) and [Pd(FIP)]Cl, that were activated against chronic myelogenous leukemia cell line, K562, were selected. Also, the interaction of these anticancer Pd(II) complexes with highly polymerized calf thymus DNA was extensively studied by means of electronic absorption, fluorescence, and circular dichroism in Tris-buffer. The results showed that the binding was positive cooperation and Pd(phen)(FIP) (K  = 127 M G = 1.2) exhibited higher binding constant and number of binding sites than [Pd(FIP)]Cl (K  = 13 M G = 1.03) upon binding to DNA. The fluorescence data indicates that quenching effect for Pd(phen)(FIP) (K  = 58 mM) was higher than [Pd(FIP)]Cl (K  = 12 mM). Also, [Pd(FIP)]Cl interacts with ethidium bromide-DNA, as non-competitive inhibition, and can bind to DNA via groove binding and Pd(phen)(FIP) can intercalate in DNA. These results were confirmed by circular dichroism spectra. Docking data revealed that longer complexes have higher interaction energy and bind to DNA via groove binding. Graphical Abstract Two anticancer Pd(II) complexes of imidazole derivative have been synthesized and interacted with calf thymus DNA. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. [Pd(FIP)]Cl can bind to DNA via groove binding while intercalation mode of binding is observed for Pd(phen)(FIP).