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KMID : 0811719980020030395
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Korean Journal of Physiology & Pharmacology
1998 Volume.2 No. 3 p.395 ~ p.401
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In vitro Cytotoxicity of Novel Platinum(II) Coordination Complexes Containing Diaminocyclohexane and Diphenylphosphines
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Jee-Chang Jung
Young-Kyu Kim/Seung-Joon Park/Joo-Ho Chung/Sung-Goo Chang/Kyung-Tae Lee/Min-Son Baek
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Abstract
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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)]ㆍ
2NO3 (KHPC-001) and [Pt(tracts-l-dach)(DPPE)]·2NO3
(KHPC-002) was evaluated and compared on various P-388 cancer cell lines and porcine
kidney cell line (LLC-PK1). 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 IC50 of the three complexes on
LLC-PK1 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-PK1. These results indicate that KHPC-001 and
KHPC-002 are a third-generation platinum complexes with potent antitumor activity and
low nephrotoxicity.
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KEYWORD
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Nephrotoxicity, Platinum coordination complex, Antitumor activity,
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