title: Synthesis of 1-naphtylpiperazine derivatives as serotoninergic ligands and their evaluation as antiproliferative agents.
abstract: 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.
authors: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors: Ferdinando
authors: F
authors: Fiorino
authors: Elisa
authors: E
authors: Magli
authors: Elisa
authors: E
authors: Perissutti
authors: Beatrice
authors: B
authors: Severino
authors: Francesco
authors: F
authors: Frecentese
authors: Antonella
authors: A
authors: Esposito
authors: Francesca
authors: F
authors: De Angelis
authors: Giuseppina Maria
authors: GM
authors: Incisivo
authors: Paola
authors: P
authors: Massarelli
authors: Cristina
authors: C
authors: Nencini
authors: Elena
authors: E
authors: Di Gennaro
authors: Alfredo
authors: A
authors: Budillon
authors: Alessandra
authors: A
authors: Di Cintio
authors: Vincenzo
authors: V
authors: Santagada
authors: Giuseppe
authors: G
authors: Caliendo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009281:Naphthalenes; D010879:Piperazines; D044282:Receptor, Serotonin, 5-HT1A