Synthesis of new β-lactam analogs and evaluation of their histone deacetylase (HDAC) activity

Abstract

A simple synthesis of the β-lactams 11-13 and 16-17 as novel histone deacetylase (HDAC) inhibitors is described. The key synthetic strategies involved the O-alkylation of 6-APA and the coupling reactions of freshly prepared N-carbobenzyloxy-L-prolines 5 and 6 and 6-aminopenicillanates 8-10 and 15 in high yields. It was found that all compounds show potent growth inhibitory activity on human tumor cell lines, the most potent compound 16 exhibiting an IC50 = 2.1 μM in vitro. © 2007 Verlag der Zeitschrift für Naturforschung.