Cell growth-inhibiting properties of selected carrier-bound, monoamine-coordinated platinum(II) compounds

In contradistinction to the ligand arrangement in coordination compounds of the square-planar cis-diamminedichloroplatinum(II) type as represented by the prototype anticancer drug cisplatin, scant attention has been paid in cancer research to those platinum complexes in which only a single amino group ( in addition to different ligands) is coordinated to the metal. In continuation of earlier research in this laboratory focused on macromolecular compounds containing monoamine-coordinated platinum, we have now synthesized a series of such polymeric platinum conjugates and assessed their antiproliferative activity in cell culture tests conducted against several human cancer cell lines. Conjugates containing hydroxylated side groups as hydrosolubilizing entities are found to exhibit poor, or no, activity up to the highest drug concentration tested ( 50 mug Pt/mL). In contrast, those conjugates in which the solubilizing units are characterized by the presence of potentially cationic tert-amine side chain terminals show remarkably high cell-killing activity, with IC50 in the range of 1 - 6 mug Pt/mL against the HeLa cervical epitheloid carcinoma line. Two selected samples tested against the A-2780 human ovarian cancer line and its cisplatin-resistant A-2780-cis counterpart shows lack of cross-resistance with cisplatin ( resistance factor less than or equal to1). These findings augur well for the development of polymer-conjugated monoamine-coordinated platinum compounds with carcinostatic properties.