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Synthesis and in vitro Evaluation of Novel Indole‐Based Sigma Receptors Ligands
Author(s) -
Yarim Mine,
Koksal Meric,
Schepmann Dirk,
Wünsch Bernard
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01215.x
Subject(s) - indole test , receptor , chemistry , stereochemistry , in vitro , cytotoxicity , proton nmr , cell culture , biochemistry , biology , genetics
To investigate the molecular features involved in sigma (σ) receptors binding, a series of compounds based on indole scaffolds were synthesized and their chemical structures were confirmed by 1 H‐NMR, IR, and elemental analysis. Their affinity toward σ 1 and σ 2 receptor subtypes was evaluated. 1‐{[4‐(2‐phenylethyl)piperazin‐1‐yl]methyl}‐3‐methyl‐1 H ‐indole 3b had a high affinity to σ 1 receptors, while three compounds, 1‐{3‐[4‐(substitutedphenyl)piperazin‐1‐yl]propyl}‐1 H ‐indole derivatives 4a– c had shown high affinity and selectivity for σ 2 receptors. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7), breast (MCF7), and colon (HCT‐116) cancer cell lines. Compound 1c (3‐{[4‐(3,4‐dichlorobenzyl)piperazin‐1‐yl]methyl}‐1 H ‐indole) showed significant cell growth inhibitory activity on the selected cancer cell lines.