2. Academic Validation
  3. Synthesis and biological evaluation of glucuronide prodrugs of the histone deacetylase inhibitor CI-994 for application in selective cancer chemotherapy

Synthesis and biological evaluation of glucuronide prodrugs of the histone deacetylase inhibitor CI-994 for application in selective cancer chemotherapy

  • Bioorg Med Chem. 2008 Sep 1;16(17):8109-16. doi: 10.1016/j.bmc.2008.07.048.
Mickaël Thomas 1,  Jonathan Clarhaut,  Isabelle Tranoy-Opalinski,  Jean-Pierre Gesson,  Joëlle Roche,  Sébastien Papot
Affiliations

Affiliation

  • 1 UMR-CNRS 6514, Synthèse et Réactivité des Substances Naturelles, Université de Poitiers, 40 Av. du Recteur Pineau, 86022 Poitiers Cedex, France.
PMID: 18692397 DOI: 10.1016/j.bmc.2008.07.048
Abstract

Two glucuronide prodrugs of the histone deacetylase inhibitor CI-994 were synthesized. These compounds were found to be soluble in aqueous media and stable under physiological conditions. The carbamoyl derivatisation of CI-994 significantly decreased its toxicity towards NCI-H661 lung Cancer cells. Prodrug incubation with beta-glucuronidase in the culture media led efficiently to the release of the parent drug and thereby restoring its ability to decrease cell proliferation, to inhibit HDAC and to induce E-Cadherin expression.

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