Synthesis, biological characterization and molecular modeling insights of spirochromanes as potent HDAC inhibitors

Florian Thaler, Loris Moretti, Raffaella Amici, Agnese Abate, Andrea Colombo, Giacomo Carenzi, Maria Carmela Fulco, Roberto Boggio, Giulio Dondio, Stefania Gagliardi, Saverio Minucci, Luca Sartori, Mario Varasi, Ciro Mercurio

Research output: Contribution to journalArticlepeer-review

Abstract

In the last decades, inhibitors of histone deacetylases (HDAC) have become an important class of anti-cancer agents. In a previous study we described the synthesis of spiro[chromane-2,4′-piperidine]hydroxamic acid derivatives able to inhibit histone deacetylase enzymes. Herein, we present our exploration for new derivatives by replacing the piperidine moiety with various cycloamines. The goal was to obtain highly potent compounds with a good in vitro ADME profile. In addition, molecular modeling studies unravelled the binding mode of these inhibitors.

Original languageEnglish
Pages (from-to)53-67
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Volume108
DOIs
Publication statusPublished - Jan 27 2016

Keywords

  • Antiproliferation
  • Epigenetics
  • Histone deacetylases
  • Molecular modeling
  • Privileged structures

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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