Synthesis, characterization, and in vitro antitumor activity of osteotropic diam(m)ineplatinum(II) complexes bearing a N,N-bis(phosphonomethyl)glycine ligand.
A series of osteotropic (bone-seeking) [(bis(phosphonomethyl)amino-kappaN)acetato-kappaO(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, (1)H, (13)C, and (31)P NMR spectroscopy. The 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-kappaN)acetato-kappaO(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) > or = cis-R,S-chxn > en.
Galanski
Mathea Sophia
MS
Institute of Inorganic Chemistry, University of Vienna, Vienna, Austria. markus.galanski@univie.ac.at
Slaby
Susanna
S
Jakupec
Michael A
MA
Keppler
Bernhard K
BK
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003514:Cyclohexylamines / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D008024:Ligands; D009943:Organophosphorus Compounds; D009944:Organoplatinum Compounds; C040598:glyphosphine; C030435:1,2-cyclohexanediamine; D005998:Glycine