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

• Bulletin of the Korean Chemical Society
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• v.30 no.10
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• pp.2303-2308
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• 2009

A thiocyanate poly(vinyl chloride) (PVC) membrane electrode based on [1,2-bis(diphenylphosphino)ethane]dihalopalladium( II), [(dppe)$PdX_2$, X = Cl ($L^1$), X = I ($L^2$)] as active sensor has been developed. The diiodopalladium complex, [(dppe)$PdI_2](L^2$) displays an anti-Hofmeister selectivity sequence: $SCN^-\;>\;I^-\;>\;{ClO_4}^-\;>\;Sal^-\;>\;Br^-\;>\;{NO_2}^-\;>\;{HPO_4}^-\;>\;AcO^-\;>\;{NO_3}^-\;>\;{H_2PO_4}^-\;>\;{CO_3}^{2-}$. The electrode exhibits a Nernstian response (-59.8 mV/decade) over a wide linear concentration range of thiocyanate ($(1.0\;{\times}\;10^{-1}\;to\;5.0\;{\times}\;10^{-6}$ M), low detection limit ($(1.1\;{\times}\;10^{-6}$ M), fast response $(t_{90%}$ = 24 s), and applicability over a wide pH range (3.5∼11). Addition of anionic sites, potassium tetrakis[p-chlorophenyl] borate (KTpClPB) is shown to improve potentiometric anion selectivity, suggesting that the palladium complex may operate as a partially charged carrier-type ionophore within the polymer membrane phase. The reaction mechanism is discussed with respect to UV-Vis and IR spectroscopy. Application of the electrode to the potentiometric titration of thiocyanate ion with silver nitrate is reported.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.59-64
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• 2011

Degree of unsaturation in fatty acid molecules plays an important role in the formation of vesicles. Vesicle formation from C18 fatty acids with different amount of double bonds such as oleic acid, linoleic acid and linolenic acid with the incorporation of 1,2-dipalmitoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DPPE-PEG2000) have been examined by TEM. Critical vesicular concentrations (CVC) of the vesicle suspension are determined by turbidity and surface tension methods. The CVC of fatty acids increases when the amount of unsaturation in the alkyl chain increases. On the other hand, stability of vesicle suspension has been examined by using particle size and zeta potential at $30^{\circ}C$. There was a dramatic decrease in particle size measurement from mono-unsaturation to tri-unsaturation which could be due to the effect of fluidity in the membrane bilayer caused by different degree of unsaturation. The values of zeta potential for vesicles that were formed without the incorporation of DPPE-PEG2000 were in the range of -70 mV to -100 mV. It has been observed that the incorporation of DPPEPEG2000 to the vesicle reduces the magnitude of zeta potential. However, this phenomenon does not obviously seen in fatty acid vesicles formed by linoleate-linoleic acid and linolenate-linolenic acid. We therefore conclude that the addition of DPPE-PEG2000 does not effectively improve the stability of the linoleate-linoleic acid and linolenatelinolenic acid vesicle at pH 9.0 after the evaluation of their particle size and zeta potential over a period of 30 days. Although the vesicles formed were not stable for more than 10 days, they have displayed the potential in encapsulating the active ingredients such as vitamin E and calcein. The results show that the loading efficiencies of vitamin E are of encouraging value.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.395-401
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• 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
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• v.23 no.8
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• pp.1177-1180
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• 2002

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.120-120
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• 1995

This study was conducted to examine novel Pt(II) complexes, (KHPC-002; [Pt(trans-1-dach) (DPPE)]. 2NO$_3$, KHPC-005;[Pt(cis-1-dach)(DPPP)]. 2NO$_3$ and KHPC-006; [Pt(cis-1-dach) (DPPE)]. 2NO$_3$) for their acute toxicities and toxicological profiles in preclinical studies. In male and female mice given a single intraperitoneal administration of KHPC-002, KHPC-005 and LHPC-006, we determined that LD$\_$50/ values of pt(II) complexes were 295.5mg/kg(M), 350.4mg/kg(F);KHPC-002, 158.7mg/kg(M), 157.7mg/kg(F); KHPC-005, 574.8mg/kg(M), 596.5 mg/kg (F); KHPC-006, respectively. In gross and histopathological examination on dead animals, no abnormal changes were observed in any organs.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.121-121
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• 1995

This study was conducted to examine novel Pt(II) complexes, (KHPC-002: [Pt(trans-1-dach) (DPPE)]. 2N0$_3$, KHPC-005: [Pt(cis-dach) (DPPE)] 2NO$_3$ and KHPC-006: [Pt(cis-dach) (DPPP)]. 2NO$_3$) for their acute toxicities. In male and female mice given a single intraperitoneal administration of KHPC-002, KHPC-005 and KHPC-006, we determined that LD$\_$50/ values of Pt(II) complexes were 295.5mg/kg(M), 350.4mg/kg(F) : KHPC-002, 596.5mg/kg(M), 674,8mg/kg(F): KHPC-005, 158.7mg/kg(M), 157.7mg/kg(F); KHPC-006, respectively. The signs of toxicity in mice observed fellowing the administration of these compounds included the followings: decreased mortor activity: abnormal gait: salviation, trasient decreased body weight. There were no treatment related specific changes in growth examination.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.399-405
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• 2000

We have synthesized a novel platinum (II) coordination complex containing trans-ι-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis (diphenylphosphino)ethane (DPPE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt (trans-ι-DACH) (DPPE)].2NO$_3$(PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against MKN-45/S, MKN-45/ADR and MKN-45/CDDP cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells, and human renal cortical tissues, determined using the MTT assaying technique, the ($^3$H)-thymidine uptake and the glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum (II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

• YAKHAK HOEJI
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• v.40 no.2
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• pp.218-224
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• 1996

This laboratory has recently reported the synthesis and in vitro antitumor activity of PT(II) complexes containing ethylenediamine and diphosphine. In view of the reports of others, cisplatin is toxic to the kidney since the kidney's vulnerability to PT(II) complexes may originate in its ability to accumulate and retain platinum to a greater degree than other organs. The in vitro cytotoxicity of these synthetic PT(II) complexes on the primary cultured proximal tubular cells of rabbit kidney and renal cortical cells of human kidney was investigated. Three endpoints for cytotoxicity tests were evaluated:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), $^3H$-thymidine uptake and the glucose consumption tests. The rank order of sensitivity exhibited $^3H$-thymidine uptake>MTT>glucose consumption test. The agents with diphosphine leaving group were significantly less cytotoxic than cisplatin. Moreover, 1,2-bis(diphenylphosphino)ethane (DPPE) exhibited less cytotoxicity than 1.3-bis (diphenylphosphino)propane (DPPP) against on rabbit and human cultured kidney cells. Based on these results, the decreased nephrotoxicity of these new complexes over cisplatin appeared to be partially attributable to a leaving group of DPPP and DPPE. This novel class of platinum compound represents a valuable lead in the development of a "third-generation" agent.

• Bulletin of the Korean Chemical Society
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• v.35 no.11
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• pp.3199-3204
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• 2014

Two novel phosphorescent heteroleptic cationic Ir(III) complexes, Ir(bt)2(dmpe) (Ir1) and Ir (bt)2(dppe) (Ir2), where bt is 2-phenylbenzothiazole, dmpe is 1,2-bis(dimethylphosphino)ethane, and dppe is 1,2-bis(diphenyl-phosphino) ethane, were designed and synthesized. Their photophysical and electrochemical properties and the X-ray structure of the Ir1 complex were investigated. The prepared Ir(III) complexes exhibited blue-green emissions at 503-538 nm with vibronic fine structures in dichloromethane solution and PMMA film, implying that the lowest excited states are dominated by ligand-based $^3{\pi}-{\pi}^*$ transitions. The ${\pi}$-acceptor ability of the diphosphine ancillary ligand leads to blue-shift emission. The room temperature photoluminescent quantum yields (PLQYs) of Ir1 and Ir2 were 52% and 45%, respectively, in dichloromethane solution. These high PLQYs resulted from steric hindrances by the bulky cationic iridium complexes. The crystal structure of Ir1 was determined by X-ray crystallography, which revealed that central iridium adopted a distorted octahedral structure coordinated with two bt ligands (N^C) and one dmpe ligand (P^P) showing cis C-C and trans N-N dispositions. The bent nature of the dmpe ligand resulted in a relatively wide bite angle of $83.83^{\circ}$ of P-Ir-P.