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

Author(s)
Mathea Sophia Galanski, Susanna Slaby, Michael Jakupec, Bernhard Keppler
Abstract

A series of osteotropic (bone-seeking) [(bis(phosphonomethyl)amino-? N)acetato-?O(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, 13C, and 31P 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-? N)-acetato-?O(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 > NH3 = cis-R,S-chxn > en.

Organisation(s)
Department of Inorganic Chemistry
External organisation(s)
University of Vienna
Journal
Journal of Medicinal Chemistry
Volume
46
Pages
4946-4951
No. of pages
6
ISSN
0022-2623
DOI
https://doi.org/10.1021/jm0308040
Publication date
2003
Peer reviewed
Yes
Austrian Fields of Science 2012
104003 Inorganic chemistry
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/a28f3c71-4a36-446b-939f-2d87a25b2524