Synthesis, Characterization, and in Vitro Antitumor Activity of Osteotropic Diam(m)ineplatinum(II) Complexes Bearing a N,N-Bis(phosphonomethyl)glycine Ligand

摘要

A series of osteotropic (bone-seeking) [(bis(phosphonomethyl)amino-κN)acetato-κO(2-)]platinum(II) complexes attached to diammine, ethane-1,2-diamine, cis-R,S-cyclohexane-1,2,-diamine, trans-S,S-cyclohexane-1,2-diamine, or trans-R,R-cyclohexane-1,2-diamine has been synthesized in accord with the concept of drug targeting and characterized by elemental analysis, ~1H, ~(13)C, and ~(31)P NMR spectroscopy. Then in vitro antitumor activity in ovarian cancer cells (CH1) has been determined by means of the MTT assay. In this cisplatin-sensitive cell line the complexes containing cyclohexane-1,2-diamine (chxn) displayed a high activity in comparison to the diammine and ethane-1,2-diamine counterparts. In agreement with structure-activity relationships of other chxn-containing platinum(II) complexes both [(bis(phosphonomethyl)amino-κN)-acetato-κO(2-)](trans-cyclohexane-1,2-diamine)platinum(II) complexes show superior potency than the corresponding cis-congener whereas the trans-R,R isomer displays the highest activity. Within the series of complexes under investigation, potency decreases depending on the coordinated amine ligand in the following order: trans-R,R-chxn > trans-S,S-chxn > NH_3 ≥ cis-R,S-chxn > en.