Synthesis and biological evaluation of new aryl-alkyl(alkenyl)-4-benzylpiperidines, novel Sigma Receptor (SR) modulators, as potential anticancer-agents

Marta Rui, Daniela Rossi, Annamaria Marra, Mayra Paolillo, Sergio Schinelli, Daniela Curti, Anna Tesei, Michela Cortesi, Alice Zamagni, Erik Laurini, Sabrina Pricl, Dirk Schepmann, Bernhard Wűnsch, Ernst Urban, Vittorio Pace, Simona Collina

Research output: Contribution to journalArticle

Abstract

In the early 2000s, the Sigma Receptor (SR) family was identified as potential “druggable” target in cancer treatment. Indeed, high density of SRs was found in breast, lung, and prostate cancer cells, supporting the idea that SRs could play a role in tumor growth and progression. Moreover, a link between the degree of SR expression and tumor aggressiveness has been postulated, justified by the presence of SRs in high metastatic-potential cancer cells. As a consequence, considerable efforts have been devoted to the development of small molecules endowed with good affinity towards the two SR subtypes (S1R and S2R) with potential anticancer activity. Herein, we report the synthesis and biological profile of aryl-alkyl(alkenyl)-4-benzylpiperidine derivatives - as novel potential anticancer drugs targeting SR. Among them, 3 (RC-106) exhibited a preclinical profile of antitumor efficacy on a panel of cell lines representative of different cancer types (i.e. Paca3, MDA-MB 231) expressing both SRs, and emerged as a hit compound of a new class of SR modulators potentially useful for the treatment of cancer disease.

Original languageEnglish
Pages (from-to)649-665
Number of pages17
JournalEuropean Journal of Medicinal Chemistry
Volume124
DOIs
Publication statusPublished - Nov 29 2016

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sigma Receptors
Antineoplastic Agents
Modulators
Cells
Neoplasms
Tumors
Oncology
Drug Delivery Systems
Lung Neoplasms
Prostatic Neoplasms
Derivatives
Molecules
Breast Neoplasms
Cell Line
Therapeutics
Growth

Keywords

  • Apoptotic pathway
  • Compound 3 (RC-106)
  • Pan-SR modulators
  • Potential anticancer property
  • S1R agonist/antagonist profile
  • Sigma Receptor (SR)

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis and biological evaluation of new aryl-alkyl(alkenyl)-4-benzylpiperidines, novel Sigma Receptor (SR) modulators, as potential anticancer-agents. / Rui, Marta; Rossi, Daniela; Marra, Annamaria; Paolillo, Mayra; Schinelli, Sergio; Curti, Daniela; Tesei, Anna; Cortesi, Michela; Zamagni, Alice; Laurini, Erik; Pricl, Sabrina; Schepmann, Dirk; Wűnsch, Bernhard; Urban, Ernst; Pace, Vittorio; Collina, Simona.

In: European Journal of Medicinal Chemistry, Vol. 124, 29.11.2016, p. 649-665.

Research output: Contribution to journalArticle

Rui, M, Rossi, D, Marra, A, Paolillo, M, Schinelli, S, Curti, D, Tesei, A, Cortesi, M, Zamagni, A, Laurini, E, Pricl, S, Schepmann, D, Wűnsch, B, Urban, E, Pace, V & Collina, S 2016, 'Synthesis and biological evaluation of new aryl-alkyl(alkenyl)-4-benzylpiperidines, novel Sigma Receptor (SR) modulators, as potential anticancer-agents', European Journal of Medicinal Chemistry, vol. 124, pp. 649-665. https://doi.org/10.1016/j.ejmech.2016.08.067
Rui, Marta ; Rossi, Daniela ; Marra, Annamaria ; Paolillo, Mayra ; Schinelli, Sergio ; Curti, Daniela ; Tesei, Anna ; Cortesi, Michela ; Zamagni, Alice ; Laurini, Erik ; Pricl, Sabrina ; Schepmann, Dirk ; Wűnsch, Bernhard ; Urban, Ernst ; Pace, Vittorio ; Collina, Simona. / Synthesis and biological evaluation of new aryl-alkyl(alkenyl)-4-benzylpiperidines, novel Sigma Receptor (SR) modulators, as potential anticancer-agents. In: European Journal of Medicinal Chemistry. 2016 ; Vol. 124. pp. 649-665.
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