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Platinum(II) Complexes with Diglycine: X-ray Crystal Structure, 15 N NMR Spectra, and Growth-Inhibitory Activity against Mouse Meth A Solid Tumor in Vivo

1997; American Chemical Society; Volume: 36; Issue: 19 Linguagem: Inglês

10.1021/ic9615180

1520-510X

Noriharu Nagao, Takao Kobayashi, Toshio Takayama, Yoshio Koike, Yukie Ono, Toshihiko Watanabe, Takeshi Mikami, Masuko Suzuki, Tatuji Matumoto, Masatoshi Watabe,

DNA and Nucleic Acid Chemistry

Two new dipeptide complexes of the form H[Pt(digly)Cl] (2) (H2digly = glycylglycine) and H[Pt(Hdigly)Cl2] (4) were newly prepared, and K[Pt(Hdigly)Cl2] (3) was isolated. Complex 1, K[Pt(digly)Cl], crystallizes in the monoclinic space group C2/c with unit cell dimensions a = 25.77(1) Å, b = 4.09(2) Å, c = 16.432(9) Å, β = 103.74(4)°, and Z = 8. Complex 3 crystallizes in the monoclinic space group P21/c with unit cell dimensions a = 8.892(5) Å, b = 11.387(4) Å, c = 9.974(4) Å, β = 105.45(4)°, Z = 4. Complex 4 crystallizes in the monoclinic space group P21/c with unit cell dimensions a = 9.311(6) Å, b = 7.737(8), c = 15.627(4) Å, β = 105.92(3)°, Z = 4. Complex 4 has the rare iminol type H2digly coordinating to Pt. The 15N chemical shifts and the coupling constants of the deprotonated coordinated amide N were obtained for the first time for these complexes. These amide peaks showed almost no coordination shift compared with the large coordination shift of the amine nitrogen. The coupling constants between Pt and deprotonated nitrogen for K[Pt(Hdipep)Cl2] were larger than those for K[Pt(dipep)Cl]. The growth inhibition assays of K[Pt(digly)Cl], K[Pt(Hdigly)Cl2], and cis-diamminedichloroplatinum(II) (cisplatin) against methylcholanthrene-induced Meth A fibrosarcoma (Meth A) solid tumor transplanted in BALB/c mice were measured. In mice, 35.9% of slight growth inhibition was observed in the group administered with K[Pt(digly)Cl] (dose of 26 mg/kg/day), and 40.6% in the group administered with K[Pt(Hdigly)Cl2] (dose of 52 mg/kg/day), and 45.3% cisplatin (dose of 10 mg/kg/day). The side effects related to the decrease in body weight are milder than that of cisplatin. Their toxicity against normal mouse bone marrow cells was measured. All of them exhibited toxicity against bone marrow cells, but K[Pt(digly)Cl] and K[Pt(Hdigly)Cl2] had only 1/10 the toxicity of cisplatin.