Synthesis and biological activity of a platinum(II) 6-Phenyl-2,2′-bipyridine complex and its dimeric analogue

Abstract

We have synthesized (pyridyl)-(6-phenyl-2,2′-bipyridine)platinum(II) hexafluorophosphate (1) and its corresponding dimer, μ-N,N′-bis(isonicotinyl)-1, 6-hexanediamino bis-[6-phenyl-2,2′-bipyridine-platinum(II)] dichloride (2). The DNA binding constants of 1 and 2 at 20°C were determined by absorption titration to be 2.25 × 104 M-1 and 3.07 × 106 M-1, respectively. Compound 1 showed an AT preference, while 2 had no base preference. The binding site sizes of 2 for [poly(dA-dT)]2, calf thymus DNA (ctDNA), and [poly(dG-dC)]2, as determined by fluorescence titration, were 6.6, 4.0, and 2.8 bp, respectively. Compound 2 probably bound to [poly(dA-dT)]2 through bisintercalation, and to [poly(dG-dC)]2 by monointercalation. Binding of DNA by both complexes is favorable, since the binding free energies of 1 and 2 were estimated to be -5.8 and -8.7 kcal mol-1, respectively. The results of viscosity measurements and gel mobility shift assay demonstrated that binding of 1 and 2 caused DNA lengthening. The cytotoxicities of the complexes in various human cancer cell lines were determined by MTT assay. Complex 2 exhibited cytotoxicity comparable to that of cisplatin, and was more toxic than I by an order of magnitude.