DNA-Binding and Thermodynamic Parameters, Structure and Cytotoxicity of Newly Designed Platinum(II) and Palladium(II) Anti-Tumor Complexes

Mansouri-Torshizi, Hassan,Saeidifar, Maryam,Khosravi, Fatemeh,Divsalar, Adeleh,Saboury, Ali.Akbar,Ghasemi, Zahra Yekke Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.3

The complexes [Pd(bpy)(Hex-dtc)]$NO_3$ and [Pt(bpy)(Hex-dtc)]$NO_3$ (bpy is 2,2'-bipyridine and Hex-dtc is hexyldithiocarbamato ligands) were synthesized and characterized by elemental analysis and spectroscopic studies. The cytotoxicity assay of the complexes has been performed on chronic myelogenous leukemia cell line, K562, at micromolar concentration. Both complexes showed cytotoxic activity far better than that of cisplatin under the same experimental conditions. The binding parameters of the complexes with calf thymus DNA (CT-DNA) was investigated using UV-visible and fluorescence techniques. They show the ability of cooperatively intercalating in CT-DNA. Gel filtration studies demonstrated that platinum complex could cleave the DNA. In the interaction studies between the Pd(II) and Pt(II) complexes with CT-DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.

Interaction Studies of a Novel, Water-Soluble and Anti-Cancer Palladim(II) Complex with Calf Thymus DNA

Mansouri-Torshizi, H.,Saeidifar, M.,Divsalar, A.,Saboury, A.A.,Shahraki, S. Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.2

We report the preparation and characterization of a new and water soluble complex of palladium(II) with 1,10- phenanthroline and butyldithiocarbamate ligands. This compound has been studied through spectroscopic techniques, $^1H$ NMR, IR, electronic spectra and elemental analysis and conductivity measurements. The complex shows 50% cytotoxic concentration ($Ic_{50}$) value against chronic myelogenous leukemia cell line, K562, much lower than that of cisplatin. Thus the mode of binding of this complex to calf thymus DNA have been extensively investigated by isothermal titration UV-visible spectrophotometry, fluorescence, gel filteration and other methods. UV-visible studies show that the complex exhibits cooperative binding with DNA and remarkably denatures the DNA at extremely low concentration ($~13\;{\mu}M$). Fluorescence studies indicate that the complex intercalate into DNA. Gel filtration studies suggest that the binding of Pd(II) complex with DNA is strong enough that it does not readily break. In these interaction studies, several thermodynamic and binding parameters are also determined which may reflect the mechanism of action of this type of compound with DNA.

DNA Binding Studies and Cytotoxicity of the Novel 1,10-phenanthroline Palladium(II) Complexes of Dithiocarbamate Derivatives

Mansouri-Torshizi, Hassan,Saeidifar, Maryam,Ghasemi, Zahra Yekke,Khastan, Mahmood,Divsalar, Adeleh,Saboury, Ali Akbar Korean Chemical Society 2011 대한화학회지 Vol.55 No.1

Two new palladium (II) complexes, [Pd (phen)(pip-dtc)]$NO_3$ and [Pd(phen)(mor-dtc)]$NO_3$, (where phen is 1,10-Phenantroline, pip-dtc is piperidinedithiocarbamate anion and mor-dtc is morpholinedithiocarbamate anion) have been synthesized and characterized by elemental analysis, spectroscopic studies (FT-IR, $^1H$ NMR, UV-Vis) and conductance measurement. In these complexes, the dithiocarbamate ligands coordinate with Pd (II) center as bidentate with two sulfur atoms. These two complexes have been tested against chronic myelogenous leukemia cell line, K562. They show $IC_{50}$ values less than cisplatin and thus the mode of binding of the complexes to calf thymus DNA (CT-DNA) were investigated by ultraviolet difference and fluorescence spectroscopy. They can denature DNA, exhibit cooperative binding and intercalate into DNA. Several binding and thermodynamic parameters are also described. 두 종류의 새로운 팔라디움(II) 착물인 [Pd(phen)(pip-dtc)]$NO_3$와 [Pd(phen)(mor-dtc)]$NO_3$ (여기서 phen은 1,10-페난트롤린, pip-dtc은 피페리딘디티오카르바메이트 음이온, mor-dtc은 모르폴린디티오카르바메이트 음이온을 가리킨다)를 합성하고 원소분석, 분광법(FT-IR, $^1H$ NMR, UV-Vis) 및 전기전도도 측정을 이용하여 특성을 조사하였다. 이 착물들에서, 디티오카르베이트 리간드는 팔라디움 (II) 중심과 두 개의 황 원자와 이중으로 배위 결합을 하고 있다. 이 착물의 세포독성을 K562 세포주를 이용하여 조사하였을 때 $IC_{50}$ 값이 시스플라틴보다 작았기 때문에 착물들의 송아지 흉선 DNA(CT-DNA)와의 결합 모드를 UV 흡광도 차이와 형광 분광법으로 조사하였다. 착물들은 DNA를 변형시키고, 협동결합을 하고, DNA에 끼어 들어간다. 또한 몇 가지 결합 및 열역학적인 변수들이 기술되었다.

Interaction Studies of a Novel, Water-Soluble and Anti-Cancer Palladim(II) Complex with Calf Thymus DNA

H. Mansouri-Torshizi,M. Saeidifar,A. Divsalar,A. A. Saboury,S. Shahraki 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.2

We report the preparation and characterization of a new and water soluble complex of palladium(II) with 1,10- phenanthroline and butyldithiocarbamate ligands. This compound has been studied through spectroscopic techniques, 1H NMR,IR, electronic spectra and elemental analysis and conductivity measurements. The complex shows 50% cytotoxic concentration (Ic50) value against chronic myelogenous leukemia cell line, K562, much lower than that of cisplatin. Thus the mode of binding of this complex to calf thymus DNA have been extensively investigated by isothermal titration UV-visible spectrophotometry, fluorescence, gel filteration and other methods. UV-visible studies show that the complex exhibits cooperative binding with DNA and remarkably denatures the DNA at extremely low concentration (~13μM). Fluorescence studies indicate that the complex intercalate into DNA. Gel filtration studies suggest that the binding of Pd(II) complex with DNA is strong enough that it does not readily break. In these interaction studies, several thermodynamic and binding parameters are also determined which may reflect the mechanism of action of this type of compound with DNA.

DNA-Binding and Thermodynamic Parameters, Structure and Cytotoxicity of Newly Designed Platinum(II) and Palladium(II) Anti-Tumor Complexes

Hassan Mansouri-Torshizi,Maryam Saeidifar,Fatemeh Khosravi,Adeleh Divsalar,Ali.Akbar Saboury,Zahra Yekke Ghasemi 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.3

The complexes [Pd(bpy)(Hex-dtc)]NO_3 and [Pt(bpy)(Hex-dtc)]NO_3 (bpy is 2,2'-bipyridine and Hex-dtc is hexyldithiocarbamato ligands) were synthesized and characterized by elemental analysis and spectroscopic studies. The cytotoxicity assay of the complexes has been performed on chronic myelogenous leukemia cell line, K562, at micromolar concentration. Both complexes showed cytotoxic activity far better than that of cisplatin under the same experimental conditions. The binding parameters of the complexes with calf thymus DNA (CT-DNA) was investigated using UV-visible and fluorescence techniques. They show the ability of cooperatively intercalating in CT-DNA. Gel filtration studies demonstrated that platinum complex could cleave the DNA. In the interaction studies between the Pd(II) and Pt(II) complexes with CT-DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.

DNA Binding Studies and Cytotoxicity of the Novel 1,10-phenanthroline Palladium(II) Complexes of Dithiocarbamate Derivatives

Hassan Mansouri-Torshizi,Maryam Saeidifar,Zahra Yekke Ghasemi,Mahmood Khastan,Adeleh Divsalar,Ali Akbar Saboury 대한화학회 2011 대한화학회지 Vol.55 No.1

Two new palladium (II) complexes, [Pd (phen)(pip-dtc)]NO_3 and [Pd(phen)(mor-dtc)]NO_3, (where phen is 1,10-Phenantroline, pip-dtc is piperidinedithiocarbamate anion and mor-dtc is morpholinedithiocarbamate anion) have been synthesized and characterized by elemental analysis, spectroscopic studies (FT-IR, ^1 H NMR, UV-Vis) and conductance measurement. In these complexes, the dithiocarbamate ligands coordinate with Pd (II) center as bidentate with two sulfur atoms. These two complexes have been tested against chronic myelogenous leukemia cell line, K562. They show IC_(50) values less than cisplatin and thus the mode of binding of the complexes to calf thymus DNA (CT-DNA) were investigated by ultraviolet difference and fluorescence spectroscopy. They can denature DNA, exhibit cooperative binding and intercalate into DNA. Several binding and thermodynamic parameters are also described.

Investigation of effects of newly synthesized Pt(2) complex against human serum albumin and Leukemia cell line of K562

( Adeleh Divsalar ),( Ali A. Saboury ),( Leila Ahadi ),( Elham Zemanatiyar ),( Hassan Mansouri Torshizi ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.11

The biological evaluation of a new synthesized Pt(II)-complex, 2,2`-bipyridin Butylglycinato Pt(II) nitrate, an anti-tumor component, was studied at different temperatures by fluorescence and far UV circular dichroism (CD) spectroscopic methods. Human serum albumin (HSA) and human tumor cell line K562 were as targets. The Pt(II)-complex has a strong ability to quench the intrinsic fluorescence of HSA. Binding and thermodynamic parameters of the interaction were calculated by fluorescence quenching method. Far-UV-CD results showed that Pt(II)-complex induced increasing in content of α helical structure of the protein and stabilized it. The 50% cytotoxic concentration (Cc50) of complex was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay at different incubation times. Also, fluorescence staining with DAPI (4,6-diamidino-2-phenylindole) revealed some typical nuclear changes, which are characteristic of apoptosis. Above results suggest that Pt (II) complex is a promising anti-proliferative agent and should execute its biological effects by inducing apoptosis. [BMB reports 2010; 43(11): 766-771]