Platinum(II) compounds with chelating ligands based on pyridine and pyrimidine: DNA and protein binding studies

Abstract

Four Pt(II) compounds (C1-C4) have been studied in their DNA and protein binding. The compounds contain chelating diimine ligands bis(pyridine-2-yl)amine, abbreviated dpa, and bis(pyrimidine-2-yl)amine, abbreviated dipm. The anions for the compounds C1 and C3 are chloride (coordinated) and nitrate (non-coordinated) for C2 and C4. Calf-thymus DNA and an abundant plasma protein have been taken as models for the two major targets for metallodrug interactions investigated by CD spectroscopy. The modifications in the carrier ligands (chloride or ammine) or ancillary secondary amines have been considered to reveal the mode of interactions. The simultaneous effects of coordinative binding and partial intercalation to DNA are evident from several spectroscopic studies. To evaluate the permeability of the cytoplasmic and cellular membrane and the transportation inside the cells, partition coefficients of the four platinum compounds were determined. Two compounds (C3 and C4) induce two-step single-strand DNA cleavage, initiated by partial intercalation. The combined effect of several binding modes towards different bio-molecules is elucidated, providing a rationale for their in vitro activity profile.

Probing the biological evaluations of a new designed Pt(II) complex using spectroscopic and theoretical approaches: human hemoglobin as a target

“…Several studies concern the structural characterization of platinated proteins (Ruimin et al, 2007). Particularly, plasma proteins such as human serum albumin (Ivanov et al, 1998;Roy, Westmaas, Hagen, van Wezel, & Reedijk, 2009), transferrin (Khalaila, Allardyce, Verma, & Dyson, 2005), cytochrome c ), ubiquitin (Zhao & King, 2011, metallothionein (Karotki & Vašák, 2008), and superoxide dismutase (Calderone, Casini, Mangani, Messori, & Orioli, 2006) were examined. These results prompted us to investigate in more detail the reactivity of these derivatives toward vital proteins.…”

Platinum-based drugs and proteins: Reactivity and relevance to DNA adduct formation

“…In particular, plasma proteins such as human serum albumin (HSA) [5, 6], tranferrin [7] and well-known model proteins such as lysozyme (LYS) [8], hemoglobin [9], cytochrome c [10], ubiquitin[11], metallothionein [12] and superoxide dismutase [13] were examined. Additional studies aimed to understand the preferential target of Pt-drugs between protein and nucleic acids.…”

Platinum(II) compounds with chelating ligands based on pyridine and pyrimidine: Synthesis, characterizations, DFT calculations, cytotoxic assays and binding to a DNA model base

“…In general the aim of much new research is primarily focused on more efficient orally administrable drugs with minimum side toxic effects and on drugs with cisplatin-resistance, or multidrug resistance surpassing properties. To reach that target, some key characteristics of the metallodrugs are ideally required [6,7].…”

“…This calculation is significant to predict and explain the mode of interaction with biomolecules. A subsequent paper will deal with the study of the DNA and protein interactions of these four compounds [17].…”