Design, synthesis and preliminary evaluation of a series of histone deacetylase inhibitors carrying a benzodiazepine ring

L. Guandalini, M. Balliu, C. Cellai, M. V. Martino, A. Nebbioso, C. Mercurio, V. Carafa, G. Bartolucci, S. Dei, D. Manetti, E. Teodori, S. Scapecchi, L. Altucci, F. Paoletti, M. N. Romanelli

Research output: Contribution to journalArticlepeer-review

Abstract

A series of new histone deacetylase inhibitors were designed and synthesized based on hybridization between SAHA or oxamflatin and 5-phenyl-1,4-benzodiazepines. The compounds were tested for their enzyme inhibitory activity on HeLa nuclear extracts, and on human recombinant HDAC1 and HDAC6. Antiproliferative activity was tested on different cancer cells types, while proapoptotic activity was primarily tested on NB4 cells. The compounds showed IC50 values similar to those of SAHA. Compound (S)-8 displayed interesting activity against hematological and solid malignancies.

Original languageEnglish
Pages (from-to)56-68
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume66
DOIs
Publication statusPublished - 2013

Keywords

  • 1,4-Benzodiazepine
  • Antiproliferative activity
  • Apoptosis
  • Enantioselectivity
  • HDAC inhibitors

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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