Evaluation of DNA Binding, Protein Interaction, and Cytotoxic Activity of a Mononuclear Copper(II) Complex

The reactivities towards DNA and protein of a benzimidazole derived mononuclear copper(II) complex, [Cu(EDTB)](NO3)(2)center dot C2H5OH (1) [EDTB = N, N, N', N'-tetrakis(2'-benzimidazolyl methyl)-1,2-ethanediamine], were investigated under physiological conditions using UV/Vis absorption, fluorescence, and circular dichroism (CD). The experimental results suggest complex 1 could strongly bind to calf thymus DNA (CT-DNA) and induce a remarkable conformational variation of DNA. The intrinsic binding constant K-b of complex 1 to DNA is 1.08(+/- 0.02) X 10(5) M-1 and the apparent binding constant K-app is 3.9 X 10(6) M-1. The strong affinity was chiefly arising from intercalation of the benzimidazole aromatic rings of ligand system of 1 with the DNA base stack. Additionally, complex 1 could also interact with bovine serum albumin (BSA) and quench the intrinsic fluorescence of BSA. At higher concentration range of complex 1 (0-210 mu M), the fluorescence quenching of BSA by complex 1 is a combined quenching (both dynamic and static) process; at lower concentration range of complex 1 (0-15 mu M), the binding process is a single static mechanism with the binding constant (K-A) ca. 10(5) M-1. Further, cytotoxic activity of complex 1 in vitro was evaluated against the human cervical cancer (HeLa), human lung cancer (A-549), and human mammary cancer (MCF-7) cell lines. The results reveal complex 1 demonstrates a significant inhibition against the three cell lines with the IC50 values falling in the 36.12-55.13 mu M range.