Cytotoxic activity of two polyaspartamide-based monoamineplatinum(II) conjugates against the HeLa cancer cell line

In this screening study in vitro, two polymer-conjugated, square-planar pla tinum(II) complexes bound to the carrier via a single primary amine ligand were tested for antineoplastic activity against the HeLa human cervical epi thelioid carcinoma cell line. In the first of these conjugates, 1-Pt, the s pacer connecting the metal complex with the carrier backbone is a short oli go(ethylene oxide) segment, whereas a long poly(ethylene oxide) chain repre sents the spacer unit in the second conjugate, 2-Pt. IC50 data, expressed a s conjugate concentration at 50% cell growth inhibition, are 48 mu g Pt ml( -1) for 1-Pt and 120 mu g Pt ml(-1) (estimated) for 2-Pt, the long tether i n the latter conjugate presumably causing retarded enzymic release and lyso somal membrane crossing of the monomeric complex, The IC50 value of 1-Pt is close to that (44 mu g Pt ml(-1)) of a similar conjugate of an earlier inv estigation, 3-Pt, in which the metal is chelated by two carrier-attached, c is-oriented amino groups in conformance with the ligand arrangement in cisp latin, It thus appears that, in the carrier-bound state, both monoamine- an d cis-diamine-coordinated platinum(II) complexes of suitable structures may well show similar biological performance patterns. Copyright (C) 1999 John Wiley & Sons, Ltd.