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Issue 6, 2015
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Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity

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Abstract

We report the synthesis and biological evaluation of a series of indole-based σ2 receptor ligands derived from siramesine. In vitro competition binding assays showed that these analogues possessed high to moderate affinity and selectivity for σ2 receptors. Structure–affinity relationship analyses of these indole-based σ2 receptor ligands were performed. In the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 1a and 1b displayed significant and comparable antiproliferative activity in DU145, MCF7 and C6 cells to siramesine. In cell cycle analyses, compounds 1a, 1b and siramesine were found to induce a G1 phase cell cycle arrest in DU145 cells using flow cytometry. The combination of 5,6-dimethoxyisoindoline scaffold and N-(4-fluorophenyl)indole moiety was identified as a new σ2 receptor ligand deserving further investigation as an antitumor agent.

Graphical abstract: Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity

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Supplementary files

Article information


Submitted
23 Feb 2015
Accepted
14 Apr 2015
First published
20 Apr 2015

This article is Open Access

Med. Chem. Commun., 2015,6, 1093-1103
Article type
Concise Article

Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity

F. Xie, T. Kniess, C. Neuber, W. Deuther-Conrad, C. Mamat, B. P. Lieberman, B. Liu, R. H. Mach, P. Brust, J. Steinbach, J. Pietzsch and H. Jia, Med. Chem. Commun., 2015, 6, 1093
DOI: 10.1039/C5MD00079C

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