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The Effects of Extending of Co-planarity in a Series of Structurally Relative Polypyridyl Palladium(II) Complexes on DNA-binding and Cytotoxicity Properties.

Shahraki S, Mansouri-Torshizi H, Sori Nezami Z, Ghahghaei A, Yaghoubi F, Divsalar A, Saboury AA, H Shirazi F - Iran J Pharm Res (2014)

Bottom Line: EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a.Several binding and thermodynamic parameters are also described.The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Sistan & Baluchestan, Zahedan, Iran.

ABSTRACT
In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA) and a series of four structurally relative palladium(II) complexes [Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB) is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline (dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These studies have been investigated by utilizing the electronic absorption spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and gel filtration techniques. a-d complexes cooperatively bind and denature the DNA at low concentrations. Their concentration at midpoint of transition, L1/2, follows the order a > b > c > d. Also the g, the number of binding sites per 1000 nucleotides, follows the order a > b ~ c > d. EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a. Several binding and thermodynamic parameters are also described. The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin.

No MeSH data available.


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Competition between a-d complexes with ethidium bromide for the binding sites of CT-DNA (Scatchard plot). In curve 1 (▲), Scatchard's plot was obtained with calf thymus DNA alone that its concentration was 60µM. In curves nos. 2(∆), 3(◊) and 4(○) respectively 50µM, 100µM, 150µM of a, 30µM, 60µM, 90µM of b, 20µM, 40µM, 60µM of c and 10µM, 20µM, 30µM of d complexes at room temperature were added.
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Figure 10: Competition between a-d complexes with ethidium bromide for the binding sites of CT-DNA (Scatchard plot). In curve 1 (▲), Scatchard's plot was obtained with calf thymus DNA alone that its concentration was 60µM. In curves nos. 2(∆), 3(◊) and 4(○) respectively 50µM, 100µM, 150µM of a, 30µM, 60µM, 90µM of b, 20µM, 40µM, 60µM of c and 10µM, 20µM, 30µM of d complexes at room temperature were added.

Mentions: Further studies to characterize the mode of binding of Pd(II) complexes to CT-DNA were carried out (24,35,43). The number of EBr molecules intercalated to CT-DNA in presence of different concentrations of the Pd(II) complex was calculated using Scatchard analysis (44). In this experiment, the wavelengths of excitation and emission were set at 540 nm and 700 nm respectively. Both have 0.5 nm slit widths. Solutions of CT-DNA, EBr and metal complexes were prepared in Tris-HCl buffer of pH 7.0. In this medium solutions of Pd(II) complexs were interacted with CT-DNA by incubating them at 300 and 310 K for 4 h, appropriate amount of EBr was then added to them and further incubated at room temperature (300 K) for 4 h and finally processed for fluorescence spectral measurement. Saturation curves of fluorescence intensity for Pd(II) complexes-DNA systems at different rf values were obtained in the presence of increased concentrations of EBr (2, 4 to …, 20 µM). The fluorescence Scatchard plots obtained for binding of EBr to CT-DNA in absence (▲) and presence (∆, ◊, ○) of various concentrations of a-d complexes were shown in Figure. 10. This figure shows that these complexes inhibit competitively the EBr binding to CT-DNA (type-A behavior) (43), where number of binding sites n, (intercept on the abscissa) remain constant and the slope of the graphs, that is Kapp, (apparent association constant) decreases with increasing the concentration of Pd(II) complexes (Table 4). This implies that all of a-d complexes are intercalating in CT-DNA and thereby competing for intercalation sites occupied by EBr. The values of Kapp and n, suggest that d is the best intercalator and for the others it varied as c > b > a. Compare their Kapp values with those of other known CT-DNA-intercalative complexes which possess analogical structure; the Pd(II) complexes in our paper have similar or stronger affinities with CT-DNA (34).


The Effects of Extending of Co-planarity in a Series of Structurally Relative Polypyridyl Palladium(II) Complexes on DNA-binding and Cytotoxicity Properties.

Shahraki S, Mansouri-Torshizi H, Sori Nezami Z, Ghahghaei A, Yaghoubi F, Divsalar A, Saboury AA, H Shirazi F - Iran J Pharm Res (2014)

Competition between a-d complexes with ethidium bromide for the binding sites of CT-DNA (Scatchard plot). In curve 1 (▲), Scatchard's plot was obtained with calf thymus DNA alone that its concentration was 60µM. In curves nos. 2(∆), 3(◊) and 4(○) respectively 50µM, 100µM, 150µM of a, 30µM, 60µM, 90µM of b, 20µM, 40µM, 60µM of c and 10µM, 20µM, 30µM of d complexes at room temperature were added.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232794&req=5

Figure 10: Competition between a-d complexes with ethidium bromide for the binding sites of CT-DNA (Scatchard plot). In curve 1 (▲), Scatchard's plot was obtained with calf thymus DNA alone that its concentration was 60µM. In curves nos. 2(∆), 3(◊) and 4(○) respectively 50µM, 100µM, 150µM of a, 30µM, 60µM, 90µM of b, 20µM, 40µM, 60µM of c and 10µM, 20µM, 30µM of d complexes at room temperature were added.
Mentions: Further studies to characterize the mode of binding of Pd(II) complexes to CT-DNA were carried out (24,35,43). The number of EBr molecules intercalated to CT-DNA in presence of different concentrations of the Pd(II) complex was calculated using Scatchard analysis (44). In this experiment, the wavelengths of excitation and emission were set at 540 nm and 700 nm respectively. Both have 0.5 nm slit widths. Solutions of CT-DNA, EBr and metal complexes were prepared in Tris-HCl buffer of pH 7.0. In this medium solutions of Pd(II) complexs were interacted with CT-DNA by incubating them at 300 and 310 K for 4 h, appropriate amount of EBr was then added to them and further incubated at room temperature (300 K) for 4 h and finally processed for fluorescence spectral measurement. Saturation curves of fluorescence intensity for Pd(II) complexes-DNA systems at different rf values were obtained in the presence of increased concentrations of EBr (2, 4 to …, 20 µM). The fluorescence Scatchard plots obtained for binding of EBr to CT-DNA in absence (▲) and presence (∆, ◊, ○) of various concentrations of a-d complexes were shown in Figure. 10. This figure shows that these complexes inhibit competitively the EBr binding to CT-DNA (type-A behavior) (43), where number of binding sites n, (intercept on the abscissa) remain constant and the slope of the graphs, that is Kapp, (apparent association constant) decreases with increasing the concentration of Pd(II) complexes (Table 4). This implies that all of a-d complexes are intercalating in CT-DNA and thereby competing for intercalation sites occupied by EBr. The values of Kapp and n, suggest that d is the best intercalator and for the others it varied as c > b > a. Compare their Kapp values with those of other known CT-DNA-intercalative complexes which possess analogical structure; the Pd(II) complexes in our paper have similar or stronger affinities with CT-DNA (34).

Bottom Line: EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a.Several binding and thermodynamic parameters are also described.The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Sistan & Baluchestan, Zahedan, Iran.

ABSTRACT
In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA) and a series of four structurally relative palladium(II) complexes [Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB) is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline (dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These studies have been investigated by utilizing the electronic absorption spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and gel filtration techniques. a-d complexes cooperatively bind and denature the DNA at low concentrations. Their concentration at midpoint of transition, L1/2, follows the order a > b > c > d. Also the g, the number of binding sites per 1000 nucleotides, follows the order a > b ~ c > d. EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a. Several binding and thermodynamic parameters are also described. The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin.

No MeSH data available.


Related in: MedlinePlus