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Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) β-glucuronide and β-galactoside for application in selective prodrug chemotherapy

2006; Elsevier BV; Volume: 17; Issue: 4 Linguagem: Inglês

10.1016/j.bmcl.2006.11.042

1464-3405

Mickaël Thomas, Freddy Rivault, Isabelle Tranoy‐Opalinski, Joëlle Roche, Jean‐Pierre Gesson, Sébastien Papot,

Inflammatory mediators and NSAID effects

The β-O-glucuronide and β-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver β-glucuronidase. On the other hand, under enzymatic cleavage of galactoside prodrug by the corresponding enzyme, a rapid release of SAHA was observed demonstrating that the β-O-galactoside of SAHA is a promising candidate for in vivo investigations.