Synthesis and antitumor efficacy of a β-glucuronidase-responsive albumin-binding prodrug of doxorubicin

  • J Med Chem. 2012 May 10;55(9):4516-20. doi: 10.1021/jm300348r.
Thibaut Legigan  1 ,  Jonathan Clarhaut ,  Brigitte Renoux ,  Isabelle Tranoy-Opalinski ,  Arnaud Monvoisin ,  Jean-Marc Berjeaud ,  François Guilhot ,  Sébastien Papot
Affiliations
  • 1. Institut de Chimie des Milieux et des Matériaux de Poitiers, IC2MP, Université de Poitiers, UMR-CNRS 7285, 4 Rue Michel Brunet, 86022 Poitiers, France.
PMID: 22515366 DOI: 10.1021/jm300348r
Abstract

In this paper we describe the synthesis and biological evaluation of the first β-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug.