Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Selective Cytotoxicity of Novel Platinum(II) Coordination Complexes Containing DL-2-Hydroxy 3-Methylbutyric Acid

DL-2 하이드록시 3-메틸 부틸산물 배위자로 한 새로운 항암성 백금(II) 착체의 위암세포와 정상신장세포에 대한 선택적 세포독성

  • 정지창 (경희대학교 의과대학 약리학 교실) ;
  • 홍언표 (경희대학교 의과대학 약학대학) ;
  • 최승기 (포천중문의과대학 약리학교실) ;
  • 장성구 (경희대학교 의과대학 비뇨기과학 교실) ;
  • 육창수 (경희대학교 의과대학 약학대학) ;
  • 노영수 (경희대학교 의과대학 약학대학)
  • Published : 2003.06.01
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Abstract

A new series of highly water soluble platinum(II) complexes[Pt(II)(DL-2-hydroxy-3-methylbutyrate)(trans-l-1,2-dimninocyc1ohexane)] (PC-1) and [Pt(II)DL-2-hydroxy-3-methylbutyrate](cis-1,2-diaminocyclohexane)](PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared(IR), $^{13}C$-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II)complexes was tested against MKN-45, MKN/ADM and MKN/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 and PC-2 showed active against MKN-45/P, MKN/ADM and MKN/CDDP human gastric cancer cell lines, and the antitumor activity of these compounds were comparable or superior to that of cisplatin. The nephrotoxicities of PC-1 and PC-2 were found quite less then that of cisplatin using MTT and [$^3H$] thymidine uptake tests in rabbit proximal tubule cells, human kidney cortical cells human renal cortical tissues. Based on these results, these novel platinum(II) complex compounds(PC-1 ＆ PC-2) represent a valuable lead in the development of the new anticancer chemotherapeutic agents capable of improving antitumor activity and low nephrotoxicity.

Keywords

References

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