In vitro cytotoxicity of novel platinum(II) coordination complexes containing diaminocyclohexane and diphenylphosphines

ABSTRACT

We have synthesized new platinum(H) 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))cntdot2NO3 (KHPC-001) and (Pt(trans-l-dach)(DPPE)) cntdot 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-PK1I 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.