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In Vitro Cytotoxicity of Novel Platinum(II) Coordination Complexes Containing Diaminocyclohexane and Diphenylphosphines

Jung, Jee-Chang   (Department of Pharmacology, School of Medicine, Kyung Hee UniversityUU0001575  ); Kim, Young-Kyu   (Department of Pharmacology, School of Medicine, Kyung Hee UniversityUU0001575  ); Park, Seung-Joon   (Department of Pharmacology, School of Medicine, Kyung Hee UniversityUU0001575  ); Chung, Joo-Ho   (Department of Pharmacology, School of Medicine, Kyung Hee UniversityUU0001575  ); Chang, Sung-Goo   (Department of Urology, School of Medicine, Kyung Hee UniversityUU0001575  ); Lee, Kyung-Tae   (Department of Biochemistry, College of Pharmacy, Kyung Hee UniversityUU0001575  ); Baek, Min-Son   (Department of Pharmacochemistry, College of Pharmacy, Kyung Hee UniversityUU0001575  ); Park, Jong-Jip   (Department of Pharmacochemistry, College of Pharmacy, Kyung Hee UniversityUU0001575  ); Rho, Young-Soo   (Department of Pharmacochemistry, College of Pharmacy, Kyung Hee UniversityUU0001575  );
  • 초록

    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.


  • 주제어

    Nephrotoxicity .   Platinum coordination complex .   Antitumor activity.  

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  • 장성구 (28)

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  • 박종집 (0)

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