Synthesis, in vitro and in vivo characterization of new benzoxazole and benzothiazole-based sigma receptor ligands

Giuseppe Romeo, Orazio Prezzavento, Sebastiano Intagliata, Valeria Pittalà, Maria N. Modica, Agostino Marrazzo, Rita Turnaturi, Carmela Parenti, Santina Chiechio, Emanuela Arena, Agata Campisi, Giovanni Sposito, Loredana Salerno

Research output: Contribution to journalArticlepeer-review


A new set of 5-chlorobenzoxazole- and 5-chlorobenzothiazole-based derivatives containing the azepane ring as a basic moiety was designed, synthesized and evaluated through binding assays to measure their affinity and selectivity towards σ 1 and σ 2 receptors. Compounds 19, 22 and 24, with a four units spacer between the bicyclic scaffold and the azepane ring, showed nanomolar affinity towards both receptor subtype and the best K i values (K i σ 1 = 1.27, 2.30, and 0.78 and K i σ 2 = 7.9, 3.8, and 7.61 nM, respectively). Evaluation of cytotoxic and apoptotic effects in MCF-7 human cancer cells was useful to assess σ 2 receptor activity, while an in vivo mice model of inflammatory pain allowed to analyze σ 1 receptor pharmacological properties. In vitro and in vivo results suggested that compound 19 is a σ 12 agonist, compound 24 a σ 1 antagonist/σ 2 agonist, whereas compound 22 might act as σ 1 antagonist/σ 2 partial agonist. Due to their pharmacological profile, a potential therapeutic application in cancer of aforesaid novel σ 12 receptor ligands, especially 22 and 24, is proposed.

Original languageEnglish
Pages (from-to)226-235
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Jul 15 2019


  • Apoptosis
  • Benzothiazole
  • Benzoxazole
  • Cancer
  • Pain
  • Sigma-1 receptors
  • Sigma-2 receptors

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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