• Proceedings of the PSK Conference
• /
• 2001.04a
• /
• pp.143.3-144
• /
• 2001

• Proceedings of the PSK Conference
• /
• 2001.04a
• /
• pp.143.1-143.1
• /
• 2001

• Proceedings of the PSK Conference
• /
• 2001.10a
• /
• pp.244.1-244.1
• /
• 2001

• Biomolecules & Therapeutics
• /
• v.5 no.2
• /
• pp.125-132
• /
• 1997

Cisplatin, a platinum-complex, is currently one of the most effective compounds used in the treat-ment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. We synthesized new Pt (II) complex analogue containing 1,2-diaminocyclohexane (DACH) as carrier ligand and 1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(cia-DACH)(DPPE)] . $2NO_3$ (PC) was synthes-ized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $_{13}$carbon nuclear magnetic resonance (NMR)] .PC demonstrated acceptable and significant antitumor activity against SKOV-3 and OVCAR-3 human ovarian carcinoma cell lines as compared with that of cisplatin. The cytotoxicity of PC in normal cells was found quite less than that of cisplatin using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ($^3$H)thymidine uptake and glucose consumption tests in rabbit renal proximal tubular cells, human renal cortical cells and tissues. In conclusion, PC is considered to be more selective cytotoxicity toward human ovarian cancer cells than normal human/rabbit kidney cells.

• Toxicological Research
• /
• v.8 no.2
• /
• pp.205-216
• /
• 1992

cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R), an antitumor platinum complex, was selected for clinical evaluation on the basis of its experimental antitumor and toxicologic profiles in preclinical studies. These studies were performed to obtain information on its toxic signs, orgnas which are mainly affected, and to estimate its lethality in mice and rats given SKI 2053R through two routes of administration. In male and female rats given a single intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were over 3.00g/kg, respectively. In male and female mice given a signle intragastrical dose of SKI 2053R, we estimated that $LD_{50}$ values were 2.44g/kg and 1.59g/kg, respectively, In a single intraperitoneal dose of SKI 2053R, we determined that $LD_{50}$ values of male and female rats were 227mg/kg and 182mg/kg, and those of male and female mice were 198mg/kg and 207mg/kg, respectively. In gross and histopathological examinations on dead animals, we found that kidney and liver were mainly affected.

• Journal of the Korean Applied Science and Technology
• /
• v.25 no.2
• /
• pp.265-268
• /
• 2008

Among the efforts to increase the efficiency of organic light-emitting device (OLED), there is a way: doping phosphorescent materials. As a phosphorescent material, complexes of heavy transition metal, platinum, were synthesized. $Cl^-$ ion and phenyl group were used as ancillary ligands with 2-(2-pyridyl)benzimidazole (pbi) as a chromophore. The complexes were analysed by FAB-mass spectrometer and absorption and emission spectra were obtained. A phenyl group was able to shift the emission band of the complex even if it's not a chromorphore.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.3
• /
• pp.395-401
• /
• 1998

We have synthesized new platinum(II) analogs containing 1,2-diaminocyclohexane (dach) as a carrier ligand, 1,3-bis(diphenylphosphino) propane (DPPP) /1,2-bis(diphenylphosphino)ethane (DPPE) as a leaving group and nitrates to improve solubility. In the present study, the cytotoxicity of $[Pt(trans-l-dach)(DPPP)]\;2NO_3$ (KHPC-001) and $[Pt(trans-l-dach)(DPPE)]\;2NO_3$ (KHPC-002) was evaluated and compared on various P-388 cancer cell lines and porcine kidney cell line ($LLC-PK_1$). The new platinum complexes demonstrated high efficacy on P-388 mouse leukemia cell line as well as cisplatin-resistant (P-388/CDDP) and adriamycin-resistant (P-388/ADR) P-388 cell lines. The intracellular platinum content was measured by a flame atomic absorption spectrophotometer (FAAS), and it was comparable to the results of $IC_{50}$ of the three complexes on $LLC-PK_1$ and P-388/S cells, while only DPPE compound was accumulated in high volume in P-388/ADR and P-388/CDDP cells. While the DNA-interstrand cross-links of KHPC-001, KHPC-002 and cisplatin were similar on P-388/S leukemia cells, these new platinum complexes were much less DNA cross-linking to a kidney derived cell line, $LLC-PK_1$. These results indicate that KHPC-001 and KHPC-002 are a third-generation platinum complexes with potent antitumor activity and low nephrotoxicity.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.3
• /
• pp.947-955
• /
• 2011

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.

• Biomolecules & Therapeutics
• /
• v.7 no.3
• /
• pp.292-299
• /
• 1999

SKI 2053 R, cis-Malonato [(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. Effects of test agent on general toxicity of does and embryonic development of Fl fetuses were investigated in rabbits. Sixty eight New Zealand white rabbits were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rabbits from days 6 to 18 of gestation at dose levels of 0, 0.67, 2.0, or 6.0 mg/kg/day. The pregnant does were subjected to the caesarean section on day 28 of gestation. No treatment-related changes in clinical signs, body weight, food consumption, and necropsy findings were observed in all groups. Fl fetuses showed no changes related to the treatment of SKI 2053R, except that an increase in the incidence of skeletal variations were observed at 6.0 mg/kg. There were no signs of material toxicity or embryotoxicity at 0.67 and 2.0 mg/kg. The results show that the administration of 6.0 mg/kg SKI 2053R induces skeletal variations in fetuses and that the no observed adverse effect levels(NOAELS) of SKI 2053R are considered to be over 6.0 mg/kg for does and 2.0 mg/kg for Fl fetuses in rabbits.

• Journal of the Korean Chemical Society
• /
• v.31 no.5
• /
• pp.444-451
• /
• 1987

The dependence of polarographic parameters on the pressure for the reduction of copper(II), cadmium(II), and zinc(II) complex ions with ethylenediamine, propylenediamine, and diethylenetriamine has been studied. In this study the dropping mercury electrode, the mercury pool electrode, and helix type of platinum wire were used as the working, the reference, and the auxilary electrode, respectively. With increasing the pressure from 1 atmosphere to 1,500 atmospheres, the reduction half-wave potentials of metal complex ions are shifted to the negative values and the diffusion currents become considerably larger, in keeping with the theory on the change of the physical properties of the electrolytic solution such as the density, the viscosity, the dielectric constant, and the electrical conductance, etc. The slope values of the logarithmic plot are increased with increasing the pressure, which indicates the more irreversible reduction. The temperature coefficients of diffusion current observed over the range of the temperature from 25$^{\circ}$C to 35$^{\circ}$C are about two percentage with increasing the pressure, therefore the polarographic reduction under the high pressure is controlled by diffusion. The linear relationships between diffusion current and concentration of metal complex ions are established over all pressure range.