Synthesis of 1-naphtylpiperazine derivatives as serotoninergic ligands and their evaluation as antiproliferative agents

Ferdinando Fiorino, Elisa Magli, Elisa Perissutti, Beatrice Severino, Francesco Frecentese, Antonella Esposito, Francesca De Angelis, Giuseppina Maria Incisivo, Paola Massarelli, Cristina Nencini, Elena Di Gennaro, Alfredo Budillon, Alessandra Di Cintio, Vincenzo Santagada, Giuseppe Caliendo

Research output: Contribution to journalArticlepeer-review


Serotonin (5-hydroxytryptamine, 5-HT) is one of the most important neuromediator involved in numerous physiological and pathophysiological processes. In addition it is well established that 5-HT acts as a growth factor on several types of non-tumoral and tumoral cells, and recently it was also related to oncogenes. 5-HT1A receptor expression was identified in prostatic tumor cell lines (PC3 cells) and in human hormone refractory prostate cancer tissue. Based on these observations, development of 5-HT1A antagonists could be useful in inhibiting the growth of cancer cells. In order to investigate on potential use of 5-HT1A ligands as antiproliferative agents, we have analyzed a new set of 1-naphtylpiperazine derivatives. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT1A and moderate to no affinity for other relevant receptors (5-HT2A, 5-HT2C, D1, D2, α1 and α2). All compounds were then evaluated in order to assess their antiproliferative activity using PC3 cells and the most active compounds (1 and 2) were fully characterized to define the mechanism responsible for the observed antiproliferative effect.

Original languageEnglish
Pages (from-to)2206-2216
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Issue number6
Publication statusPublished - Jun 2011


  • 5-HT ligands
  • Antiproliferative agents
  • Naphtylpiperazine
  • PC3 cells

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology


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