Synthesis and in vitro evaluation of novel indole-based sigma receptors ligands

Yarim M., Koksal M., Schepmann D., Wünsch B.

Chemical Biology and Drug Design, cilt.78, sa.5, ss.869-875, 2011 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 78 Sayı: 5
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1111/j.1747-0285.2011.01215.x
  • Dergi Adı: Chemical Biology and Drug Design
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.869-875
  • Anahtar Kelimeler: cytotoxicity assay, drug design, indole, piperazine, radio ligand binding assay, radioligands, sigma ligands
  • İstanbul Medipol Üniversitesi Adresli: Hayır

Özet

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 1H-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-1H-indole 3b had a high affinity to σ 1 receptors, while three compounds, 1-{3-[4-(substitutedphenyl)piperazin-1-yl]propyl}-1H-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}-1H-indole) showed significant cell growth inhibitory activity on the selected cancer cell lines. © 2011 John Wiley & Sons A/S.