Platinum(II) Complexes with Diglycine: X-ray Crystal Structure, 15N NMR Spectra, and Growth-Inhibitory Activity against Mouse Meth A Solid Tumor in Vivo
详细信息 查看全文
- 作者：Noriharu Nagao ; Takao Kobayashi ; Toshio Takayama ; Yoshio Koike ; Yukie Ono ; Toshihiko Watanabe ; Takeshi Mikami ; Masuko Suzuki ; Tatuji Matumoto ; and Masatoshi Watabe
- 刊名：Inorganic Chemistry
- 出版年：1997
- 出版时间：September 10, 1997
- 年：1997
- 卷：36
- 期：19
- 页码：4195 - 4201
- 全文大小：145K
- 年卷期：v.36,no.19(September 10, 1997)
- ISSN：1520-510X
文摘
Two new dipeptide complexes of the formH[Pt(digly)Cl] (2)(H2digly = glycylglycine) andH[Pt(Hdigly)Cl2](4) were newly prepared, andK[Pt(Hdigly)Cl2] (3) wasisolated. Complex 1, K[Pt(digly)Cl],crystallizes in themonoclinic space group C2/c with unit celldimensions a = 25.77(1) Å, b =4.09(2) Å, c = 16.432(9) Å, 
=103.74(4)
, and Z = 8. Complex 3crystallizes in the monoclinic space groupP21/c with unit cell dimensionsa= 8.892(5) Å, b = 11.387(4) Å, c= 9.974(4) Å, = 105.45(4), Z = 4.Complex 4 crystallizes in the monoclinicspace group P21/c with unit celldimensions a = 9.311(6) Å, b =7.737(8), c = 15.627(4) Å, =105.92(3), Z= 4. Complex 4 has the rare iminol typeH2digly coordinating to Pt. The 15Nchemical shifts and the couplingconstants of the deprotonated coordinated amide N were obtained for thefirst time for these complexes. Theseamide peaks showed almost no coordination shift compared with the largecoordination shift of the amine nitrogen.The coupling constants between Pt and deprotonated nitrogen forK[Pt(Hdipep)Cl2] were larger than thoseforK[Pt(dipep)Cl]. The growth inhibition assays ofK[Pt(digly)Cl], K[Pt(Hdigly)Cl2],and cis-diamminedichloroplatinum(II) (cisplatin) against methylcholanthrene-induced Meth Afibrosarcoma (Meth A) solid tumor transplantedin BALB/c mice were measured. In mice, 35.9% of slight growthinhibition was observed in the group administeredwith K[Pt(digly)Cl] (dose of 26 mg/kg/day), and 40.6% inthe group administered with K[Pt(Hdigly)Cl2](doseof 52 mg/kg/day), and 45.3% cisplatin (dose of 10 mg/kg/day). Theside effects related to the decrease in bodyweight are milder than that of cisplatin. Their toxicity againstnormal mouse bone marrow cells was measured.All of them exhibited toxicity against bone marrow cells, butK[Pt(digly)Cl] and K[Pt(Hdigly)Cl2]had only 1/10the toxicity of cisplatin.
=103.74(4), and Z = 8. Complex 3crystallizes in the monoclinic space groupP21/c with unit cell dimensionsa= 8.892(5) Å, b = 11.387(4) Å, c= 9.974(4) Å, = 105.45(4), Z = 4.Complex 4 crystallizes in the monoclinicspace group P21/c with unit celldimensions a = 9.311(6) Å, b =7.737(8), c = 15.627(4) Å, =105.92(3), Z= 4. Complex 4 has the rare iminol typeH2digly coordinating to Pt. The 15Nchemical shifts and the couplingconstants of the deprotonated coordinated amide N were obtained for thefirst time for these complexes. Theseamide peaks showed almost no coordination shift compared with the largecoordination shift of the amine nitrogen.The coupling constants between Pt and deprotonated nitrogen forK[Pt(Hdipep)Cl2] were larger than thoseforK[Pt(dipep)Cl]. The growth inhibition assays ofK[Pt(digly)Cl], K[Pt(Hdigly)Cl2],and cis-diamminedichloroplatinum(II) (cisplatin) against methylcholanthrene-induced Meth Afibrosarcoma (Meth A) solid tumor transplantedin BALB/c mice were measured. In mice, 35.9% of slight growthinhibition was observed in the group administeredwith K[Pt(digly)Cl] (dose of 26 mg/kg/day), and 40.6% inthe group administered with K[Pt(Hdigly)Cl2](doseof 52 mg/kg/day), and 45.3% cisplatin (dose of 10 mg/kg/day). Theside effects related to the decrease in bodyweight are milder than that of cisplatin. Their toxicity againstnormal mouse bone marrow cells was measured.All of them exhibited toxicity against bone marrow cells, butK[Pt(digly)Cl] and K[Pt(Hdigly)Cl2]had only 1/10the toxicity of cisplatin.