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.
| Original language | English |
|---|---|
| Pages (from-to) | 2206-2216 |
| Number of pages | 11 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 46 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2011 |
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Keywords
- 5-HT ligands
- Antiproliferative agents
- Naphtylpiperazine
- PC3 cells
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Pharmacology
Cite this
Synthesis of 1-naphtylpiperazine derivatives as serotoninergic ligands and their evaluation as antiproliferative agents. / Fiorino, Ferdinando; Magli, Elisa; Perissutti, Elisa; Severino, Beatrice; Frecentese, Francesco; Esposito, Antonella; De Angelis, Francesca; Incisivo, Giuseppina Maria; Massarelli, Paola; Nencini, Cristina; Di Gennaro, Elena; Budillon, Alfredo; Di Cintio, Alessandra; Santagada, Vincenzo; Caliendo, Giuseppe.
In: European Journal of Medicinal Chemistry, Vol. 46, No. 6, 06.2011, p. 2206-2216.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis of 1-naphtylpiperazine derivatives as serotoninergic ligands and their evaluation as antiproliferative agents
AU - Fiorino, Ferdinando
AU - Magli, Elisa
AU - Perissutti, Elisa
AU - Severino, Beatrice
AU - Frecentese, Francesco
AU - Esposito, Antonella
AU - De Angelis, Francesca
AU - Incisivo, Giuseppina Maria
AU - Massarelli, Paola
AU - Nencini, Cristina
AU - Di Gennaro, Elena
AU - Budillon, Alfredo
AU - Di Cintio, Alessandra
AU - Santagada, Vincenzo
AU - Caliendo, Giuseppe
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - 5-HT ligands
KW - Antiproliferative agents
KW - Naphtylpiperazine
KW - PC3 cells
UR - http://www.scopus.com/inward/record.url?scp=79955577254&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955577254&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2011.03.001
DO - 10.1016/j.ejmech.2011.03.001
M3 - Article
VL - 46
SP - 2206
EP - 2216
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 6
ER -