Synthesis and biological activity of novel platinum(II) complexes of glutamate tethered to hydrophilic hematoporphyrin derivatives

Abstract

A new series of hematoporphyrin-platinum(II) conjugates was prepared by platination of the glutamate ligand tethered to hydrophilic hematoporphyrin derivatives, in which different numbers of ethylene oxide unit were introduced to modulate the hydrophobic/hydrophilic balance of the conjugates. The antitumor activity of the hematoporphyrin-platinum(II) conjugates was assayed in vitro and in vivo against the leukemia L1210 cell line. Among the complexes, compound 11 exhibited not only higher in vivo activity (T/C%=192) than cisplatin (T/C%=184) and carboplatin (T/C%=168), but also elevated tumor-localizing effect (tumor/muscle ratio >3). © 2004 Elsevier Ltd. All rights reserved.