Cytotoxic activity of two polyaspartamidebased monoamineplatinum(II) conjugates against the HeLa cancer cell line

Abstract

In this screening study in vitro, two polymerconjugated, square-planar platinum(II) complexes bound to the carrier via a single primary amine ligand were tested for antineoplastic activity against the HeLa human cervical epithelioid carcinoma cell line. In the first of these conjugates, 1-Pt, the spacer connecting the metal complex with the carrier backbone is a short oligo(ethylene oxide) segment, whereas a long polyethylene oxide) chain represents the spacer unit in the second conjugate, 2-Pt. IC50 data, expressed as conjugate concentration at 50% cell growth inhibition, are 48 μg Pt ml-1 for 1-Pt and 120 μg Pt ml-1 (estimated) for 2-Pt, the long tether in the latter conjugate presumably causing retarded enzymic release and lysosomal membrane crossing of the monomeric complex. The IC50 value of 1-Pt is close to that (44 μg Pt ml-1) of a similar conjugate of an earlier investigation, 3-Pt, in which the metal is chelated by two carrier-attached, cis-oriented amino groups in conformance with the ligand arrangement in cisplatin. It thus appears that, in the carrier-bound state, both monoamine- and cis-diamine-coordinated platinum(II) complexes of suitable structures may well show similar biological performance patterns. Copyright © 1999 John Wiley & Sons, Ltd.