Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents

Aldo Bianchi, Marcello Ugazzi, Luca Ferrante, Daniele Lecis, Cinzia Scavullo, Eloise Mastrangelo, Pierfausto Seneci

Research output: Contribution to journalArticlepeer-review

Abstract

A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF 3 substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency.

Original languageEnglish
Pages (from-to)2204-2208
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number6
DOIs
Publication statusPublished - Mar 15 2012

Keywords

  • Apoptosis
  • IAP inhibitors
  • Oncology
  • Peptidomimetics
  • Smac mimetics

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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