Synthesis, antitumor activity and acute toxicity of diammine/diamino-cyclohexane platinum(II) complexes with oxygen-ligating leaving group.

ABSTRACT

In order to clarify the relation between the reactivity of the leaving groups in cisplatin-like complexes and their activity / toxicity, six new complexes of the formula Pt(NH3)2X and Pt(dach)X (where X is selenato, anion of squaric acid, or demethylcantharic acid) have been synthesized and compared. These complexes have been characterized by elemental analysis, infrared spectroscopy, and conductivity measurements. Six human neoplastic cell lines (HCT, KB, BGC, HL-60, K-563 and Bel-7402) were used to screen these compounds. The results demonstrated that four of them have comparable IC50 and even lower IC50 in a few kinds of tumor cell lines compared to cisplatin. Their LD50 values showed that the toxicity of these platinum complexes is related to the reactivity of the leaving groups. All of these complexes have lower acute toxicity than cisplatin, but the anticancer activity is not affected.