Targeting CT-DNA with Novel Dafone–Pd(II) Complexes: In Vitro Cytotoxicity, In Vivo Efficacy, and Computational Insight

The
novel complexes [Pd(bpy)(daf)](NO3)2 (1) and [Pd(daf)(dpa)](NO3)2 (2) (where bpy is 2,2’-bipyridine, daf is 4,5-diazaflourene-9-one
(dafone), and dpa is 2,2’-dipyridylamine) were synthesized
and studied using various methods. The cytotoxic effects of these
complexes were investigated on two different cell types, colon cancer
cells and NIH/3T3 fibroblasts, and compared with those of cisplatin.
In vivo experiments did not show acute hepatorenal toxicity. Various
spectroscopic, viscosity, and computational methods were employed
to characterize the CT-DNA binding profile of the complexes. The experimental
and theoretical results are mutually supportive and show that the
complexes interact effectively with CT-DNA. According to the absorption
study, the complexes interact with CT-DNA predominantly via a groove
binding mode. The fluorescence spectroscopy data suggest static quenching
as the underlying mechanism for the fluorescence quenching of the
DNA system. The complexes primarily interact with CT-DNA via hydrogen
bonding and van der Waals forces.