• 한국환경보건학회지
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• 제24권3호
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• pp.26-34
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• 1998

Diethanolamine Dithiocarbamate containing OH groups which gave water-soluble [Pt(dtc)$_{2}$] (diethanolamine dithiocarbamate) were synthesized from the reaction of CS$_{2}$ with diethanolamine. The complex has been characterized by elemental analysis, electrical conductivity, and spectroscopic results. Diethanolamine dithiocarbamate is effective as rescue and inhibition of cis-[$Pt(NH_{3})_{2}Cl_{2}$] nephrotoxicity in rats. It is suggested that diethanolamine dithiocarbamare removes platinum(II) complex coordinated to -SH groups of protein of kidney tubule cells.

• 대한화학회지
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• 제34권6호
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• pp.539-547
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• 1990

DNA base인, Adenine, Guanine 그리고 Cytosine과 diaminecytosineplatinum(DCP)의 상호작용을 SC-MEH 방법에 의하여 계산한 결과, DNA base와 DCP 결합력의 크기는 guanine > adenine > cytosine임을 알 수 있었고, cis-백금(II)착물이 trans-백금(II) 착물보다 안정화에너지가 더 크게 나타남을 adenine-DCP 착물계에서 볼 수 있었다. DNA bases ring의 atomic charge는 백금(II)착물의 배위에 의해 많은 charge 변화가 있음을 관찰하였고, 이 효과에 의하여 백금(II)착물의 항암성 메카니즘을 설명할 수 있었다.

• 약학회지
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• 제43권3호
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• pp.369-377
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• 1999

A new series of highly water soluble platinum(II) complexes {Pt(II)[1,3-bis(phenylthio) propane](trans- -1,2-diaminocyclohexane) (PC-1) and Pt(II)[1,3-bis-(phenythio)propane] cis-1,2-diaminocyclohexane(PC-2)} were synthesized, and characterized by their elemental analysis and by various spectroscopic techniques[infrared(IR), 13C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II) complexes was tested against P-388 and L-1210 mouse lymphocytic leukemia cell lines, PC-14 / P, PC-14/ADM and PC-14 / CDDP human pulmonary adenocarcinima, DU-145 human prostate carcinoma, HT-1376 human bladder carcinoma, ZR-75-1 human breast carcinoma, MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 showed active against L-1210, P-388 leukemia, human lung, stomach, prostate, bladder and breast cancer cell lines, and the antitumor activity of these compounds were comparable or superior to those of PC-2 and displatin. The nephrotoxicities of PC-1 and PC-2 were found quite less than that of cisplatin using MTT and [3H] thymidine uptake in rabbit proximal tubule cells and human kidney cortical cells. Based on these results, this novel platinum (II) complex compound (PC-1) represents a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Environmental Analysis Health and Toxicology
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• 제13권3_4호
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• pp.87-94
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• 1998

The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.73-73
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• 1993

As part of a research program to develope 3rd generation anti tumor platinum complexes, a series of platinum complexes which have 4, 5-bis-(aminomethyl)- 1, 3-dioxolane derivatives as bidenate amine ligands, represented by the general structual formula was prepared. The R$_1$ and/or R$_2$ substituents in this series of platinum complexes can be hydrogen. alkyl, of jointly formed cyclohexane. Two Xs can be a bidenate leaving ligand such as 1, 1-cyclobutanedicarboxylate, malonate, dimethylmalonate, ethylmalonate, glycolate, L-lactate, or N-methyliminodiacetate. From based on the pharmacological and toxicological studies, we have chosen SKI 2053R, cis-malonato[(4R, 5R)-4, 5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane] platinum(II) complex (NSC D644591) as a candidate for clinical evaluation. The antitumor activity of a new anti tumor platinum complex, cis-malonato [(4R, 5R)-4, 5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane] platinum(II) (SKI 2053R, NSC D644591), was compared with those of cisplatin and carboplatin using murine tumors. We evaluated three platinum complexes against L1210/CPR, a subline of L1210 leukemia resistant to cisplatin for their abilities to overcome tumor resistance to cisplatin. The in vitro cytotoxicity of SKI 2053R to L1210 cell line was 2.5-fold less potent thann that of cisplatin, and was 10-fold more cytotoxic than that of carboplatin. SKI 2053R retained similar cytotoxic effect and anti tumor activity to L1210/CPR cell line, like the cytotoxicity of SKI 2053R to L1210 cell line, while either cisplatin or carboplatin had not property to overcome the acquired cisplatin-resistance. SKI 2053R exhibited greater or comparable antitumor activity than cisplatin or carboplatin in murine tumor models.

• 약학회지
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• 제42권5호
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• pp.494-499
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• 1998

As part of a drug discovery program to discover more effective platinum-based anticancer drugs, a series of platinum complexes of 1,2-bis(diphenylphosphino)ethane(1,2-diaminopro pane)platinum(II)dinitrate (KHPC-070) has been evaluated in vitro against various tumor cell lines and normal kidney cells. The structure of this new compound was determined by elemental analysis, infrared spectroscopy (IR) and $^{13}carbon$ nuclear magnetic resonance (NMR). With the use of nine tumor cell lines, KHPC-070 exhibited a comparable cytotoxic to cisplatin. The cytotoxicity of KHPC-070 in normal cells was quite less than that of cisplatin using 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and [$^3H$]-thymidine uptake tests in rabbit renal proximal tubular cells and human renal cortical cells. Based on these results, KHPC-070 is considered to have more selective cytotoxicity toward cancer cells than normal human/rabbit kidney cells.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.111-111
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• 1997

As part of a drug discovery program to develope more effective platinum-based anticancer drugs, a series of platinum complexes trans-diaminocyclohexane platinum bi sdiphenylphosphino - ethane ( KHPC- 002) cis-diaminocyclohexane platinum bi sdiphenylphosphino - ethane ( KHPC- 006) has been evaluated in vitro against 4 human carcinoma cell lines with those of cisplatin using a tetrazolium-based colorimetric assay (MTT assay). The cell lines were two human bladder carcinoma cell lines, HT-1197 and HT-1376, human colon carcinoma cell line, HCT-116, and prostate cancer cell line DU-145. in vitro cytotoxic potential of each platinum complex was expressed as the cytotoxicity index (Cl, %).

• Bulletin of the Korean Chemical Society
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• 제28권4호
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• pp.679-681
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• 2007

• Environmental Analysis Health and Toxicology
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• 제8권3_4호
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• pp.33-41
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• 1993

This study was designed to determine the hemolytic mechanism of antitumor agent tetraphosphine platinum (II) complex (RC-1), which was synthesized recently. Erythrocytes treated with RC-1 showed concentration and time dependent lipid peroxydation, methemoglobin synthesis and hemolysis. And also treatment of radical scavengers showed the inhibitory effect of hemolysis and the decrease of malondialdehyde levels in RC-1 treated erythrocytes. So, the mechanism of hemolysis was considered to be the generation of free radicals, methemoglobin synthesis and the lipid peroxidation of phospholipid which composed of erythrocyte membrane.

• 약학회지
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• 제44권5호
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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.