Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin.

Thibaut Legigan (1) , Jonathan Clarhaut (1) , Brigitte Renoux (1) , Isabelle Tranoy-Opalinski (1) , Arnaud Monvoisin (1) , Jean-Marc Berjeaud (2) , François Guilhot (1) , Sébastien Papot (1)

1 OrgaSynth - Synthèse organique [E5 – IC2MP équipe 5]
2 MDE - Microbiologie de l'Eau [Équipe du laboratoire EBI Poitiers]

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.

Domaines: Chimie organique; Autre; Chimie

Thibaut Legigan, Jonathan Clarhaut, Brigitte Renoux, Isabelle Tranoy-Opalinski, Arnaud Monvoisin, et al.. Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin.. Journal of Medicinal Chemistry, 2012, 55 (9), pp.4516-20. ⟨10.1021/jm300348r⟩. ⟨hal-00710692⟩