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Boccarelli, A ; Coluccia, M ; Intini, FP ; Natile, G ; Locker, D ; Leng, M

Cytotoxicity and DNA binding mode of new platinum-iminoether derivatives with different configuration at the iminoether ligands

Anti-Cancer Drug Design 14 (3) 253-264

par Administrateur - publié le

Abstract :

The platinum-iminoether complexes trans-[PtCl2E-HN=-C(OEt)Me(2)] (1) and trans-[PtCl2Z-HN=C(OEt)Me(2)] (2), differing in the configuration of the iminoether ligands, were investigated for cytotoxicity towards human tumor cell lines, the involvement of DNA as a cytotoxic target, and their DNA binding mode. The cytotoxicity of isomer 1 was comparable to that of cisplatin, whereas isomer 2 was slightly less active. Excision-repair-deficient xeroderma pigmentosum group A cells were four times more sensitive to both isomers than normal cells, thus implicating cellular DNA as the cytotoxic target. Replication mapping experiments showed that both isomers interact preferentially with guanine residues at py-G-py sites.