Structural characterization, kinetic studies, and in vitro biological activity of new cis-diamminebis-cholylglycinate(O,O') Pt(II) and cis-diamminebis-ursodeoxycholate(O,O') Pt(II) complexes.
The complexes cis-diamminebis-cholylglycinate (O,O') [Pt(II) C(52)H(90)N(4)O(12)Pt, for convenience referred to as Bamet-R1] and cis-diamminebis-ursodeoxycholate (O,O') Pt(II) (C(48)H(84)N(2)O(8)Pt, Bamet-UD2) were prepared. The structural integrity of the compounds was confirmed by elemental analysis, FT-IR, NMR, FAB-MS, and UV spectroscopies. The kinetic study of both compounds was accomplished by combining the conductivity measurement and those of the analysis of the electronic spectra in aqueous solution for NaCl concentrations of 4 mM (similar to cytoplasmatic concentration), 150 mM (similar to plasmatic concentration), and 500 mM. In water, the compound Bamet-R1 showed a half-life, t(1/2), of 3.0 h. This compound forms the chelate species through loss of a ligand, and the other one acts as a bidentate ligand. Ring opening in the presence of chloride ion was produced with a k(Cl)()-of 0.25 M(-)(1) h(-)(1). The half-life of Bamet-UD2 in aqueous solution was 3.2 h. However, since this species is not able to chelate and has a lower degree of solubility in the presence of chloride ion, its kinetic behavior was very different from that of the other compound. We consider this to be of great interest with regards to its cytostatic activity. All kinetic measurements were performed under pseudo-first-order conditions, and a pseudo-first-order behavior was found. The antitumoral effect of Bamet-UD2 on several cell lines derived from rat hepatoma, human hepatoma, mouse leukemia, and human colon carcinoma was found to be, in general, similar to that of cisplatin, but higher than that observed for Bamet-R1.
Criado
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JJ
Departamento de Química Inorgánica, Departamento de Fisiología y Farmacología, and Departamento de Química Orgánica, Campus Miguel de Unamuno, Universidad de Salamanca, 37007-Salamanca, Spain. jjct@gugu.usal.es
Domínguez
M F
MF
Medarde
M
M
Fernández
E R
ER
Macías
R I
RI
Marín
J J
JJ
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives*; D006000:Glycocholic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry*; D051381:Rats; D013055:Spectrophotometry, Infrared; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000737:chemistry
D009944:Organoplatinum Compounds; C408381:diamminebis(cholylglycinate(O,O'))platinum(II); C408382:diamminebis(ursodeoxycholate(O,O'))platinum(II); D014580:Ursodeoxycholic Acid; D006000:Glycocholic Acid; D002945:Cisplatin