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Leng, M ; Locker, D ; Giraud-Panis, MJ ; Schwartz, A ; Intini, FP ; Natile, G ; Pisano, C ; Boccarelli, A ; Giordano, D ; Coluccia, M

Replacement of an NH3 by an iminoether in transplatin makes an antitumor drug from an inactive compound

Molecular Pharmacology 58 (6) 1525-1535

par Administrateur - publié le

Abstract :

To investigate the modifications of antitumor activity and DNA binding mode of transplatin after replacement of one nonleaving group NH3 by an iminoether group, trans-[PtCl2Z-HN=C(OMe)Me( NH3)] and trans-[PtCl2E-HN=C(OMe)Me(NH3)] complexes (differing in the Z or E configuration of iminoether, and abbreviated mixed Z and mixed E, respectively), have been synthesized. In a panel of human tumor cell lines, both mixed Z and mixed E show a cytotoxic potency higher than that of transplatin, the mean IC50 values being 103, 37, and 215 muM, respectively. In vivo mixed Z is more active and less toxic than mixed E in murine P388 leukemia and retains its efficacy against SK-OV-3 human cancer cell xenograft in nude mice.