Mitomycin antitumor compounds. 2. Interaction of transition metal ions with mitomycin C. Solution structure and biological activity of a Pd(2+)-MMC complex.
Interactions of Cu(2+), Zn(2+), and Pd(2+) ions with the antitumor compound mitomycin C (MMC) have been investigated by UV-vis, circular dichroism, and (13)C NMR spectroscopy. While Zn(2+) and Cu(2+) neither interacted with MMC nor catalyzed the formation of mitosenes, Pd(2+) induced strong MMC spectral modifications, suggesting the formation of a major complex, in which MMC acted as a bidentate ligand through N(1) and N(4) atoms. The coordination mode in this complex was solvent dependent: in MeOH, the NH(2) of the carbamate function was also involved as a third coordination site whereas, in H(2)O, Pd(2+) hydrolysis was more effective, leading to the replacement of the carbamoyl NH(2) function with either H(2)O or OH(-) ligands. Although coordination of the indoline nitrogen prevented methanol elimination and consequent aziridino ring opening, Pd(2+) complexation maintained MMC biological activity against cancer cells, as shown by IC(50) values. This suggests that alternative mechanisms in the biological activity of MMC should be explored.
Fiallo
Marina M L
MM
LCMB, Département de Chimie, Institut Universitaire Technologique, Université Paul Sabatier, avenue Georges Pompidou, BP 258, 81104 Castres, France. marine.fiallo@iut-tlse3.fr
Deydier
Eric
E
Bracci
Michela
M
Garnier-Suillerot
Arlette
A
Halvorsen
Karin
K
D002455:Cell Division / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol; D016685:Mitomycin / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D010165:Palladium; D012996:Solutions; D014867:Water
D008024:Ligands; D009942:Organometallic Compounds; D012996:Solutions; D014867:Water; D016685:Mitomycin; D010165:Palladium; D000432:Methanol