Biological Evaluation and Interaction of a Newly Designed Anti-cancer Pd(II) Complex and Human Serum Albumin

Abstract

The pharmacokinetics and pharmacodynamics of any drug will depend, largely, on the interaction that has with human serum albumin (HSA), the most abundant plasma protein. The interaction between newly synthesized Pd(II) complexe, 2,2'-bipyridin Butylglycinato Pd(II) nitrate, an anti-tumor component, with HSA was studied at different temperatures by fluorescence, far UV circular dichroism (CD), UV-visible spectrophotometry and theoretical approaches. The Pd(II) complex has a strong ability to quench the intrinsic fluorescence of HSA through a dynamic quenching procedure. The binding parameters and thermodynamic parameters, including δH°, δS° and δG° were calculated by fluorescence quenching method, indicated that hydrophobic forces play a major role in the interaction of Pd(II) complex with HSA. Based on Autodock, FRET (fluorescence resonance energy transfer) and fluorescence quenching data, it may be concluded that one of the binding sites in the complex of HSA is near the only one Trp of HSA (Trp214) in sub domain IIA of the protein. Far-UV-CD results indicated that Pd(II)-complex induced increase in the α-helical content of the protein. The anti-tumor property of the synthesized Pd(II) complex was studied by testing it on human tumor cell line K562. The 50% cytotoxic concentration (Cc₅₀) of complex was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Also, fluorescence staining with DAPI (4,6-diamidino-2-phenylindole) revealed some typical nuclear changes that are characteristic of apoptosis which is induced at Cc₅₀ concentration of Pd(II) complex in K562 cell line after 24 h incubation. Our results suggest that Pd(II) complex is a promising anti-proliferative agent and should execute its biological effects by inducing apoptosis.

Pt(IV), Pd(II), and Rh(III) complexes induced oxidative stress and cytotoxicity in the HCT-116 colon cancer cell line

“…Similar, pyridine-based ligands showed antitumor activity against various types of cancer cells. 2,2′-Bipyridine complexed to Pd(II) showed great anticancer activity against human leukemic K562 cells (Disalvar et al, 2011). Similarly, terpyridine complexed to Pd(II) revealed significant activity against MDA-MB-231 and MCF-7 breast cancer cell lines (Ulukaya et al, 2011a) and A549, H1299, and PC-3 nonsmall-cell lung cancer cell lines (Ulukaya et al, 2011b) with IC 50 values comparable to our results obtained on the colorectal cancer line HCT-116 with Pd(II).…”

Aromatic amine N-oxide organometallic compounds: searching for prospective agents against infectious diseases

“…Gasteiger-Marsilli charges were used and parameters for Pt(II) and Pd(II) were included in AutoDock parameter file (R ii and ε ii values for Pt(II) were based on AutoDock parameters for transition metals, 46 a set of parameters developed by Divsalar et al were used for Pd(II), with R ii = 2.50 Å and ε ii = 0.458 kcal mol −1 (ref. 47). A Lamarckian genetic algorithm with a population size of 150 individuals and 2.5 × 10 6 energy evaluations was applied for 50 search runs.…”

Synthesis, Characterization, Speciation, DNA Cleavage, and Cytotoxic Studies of the Pd[2‐(2‐Aminoethyl)‐1‐methylpyrrolidine]Cl2 Complex with Reference to Carboplatin

“…The corresponding Pd II derivatives were also used for the treatment of cancer owing to their structural analogy , . Palladium complexes are expected to have lower kidney toxicity than cisplatin because the tightly bound chelate ligands of Pd II are not easily displaced by sulfhydryl groups in kidney tubules . A number of Pd II complexes with aromatic N‐ and N,N‐containing ligands, such as derivatives of pyridine, quinoline, pyrazole, and 1,10‐phenthroline, as well as those with N,S‐chelating ligands, such as derivatives of thiosemicarbazones and dithiocarbamates, have shown very promising antitumor properties …”