Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, 34755 Kayisdagi, Istanbul, Turkey.
Chem Biol Drug Des. 2011 Nov;78(5):869-75. doi: 10.1111/j.1747-0285.2011.01215.x. Epub 2011 Sep 26.
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-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.
为了研究与 sigma (σ) 受体结合相关的分子特征，我们合成了一系列基于吲哚骨架的化合物，并通过 (1) H-NMR、IR 和元素分析确认了它们的化学结构。评估了它们对 σ(1)和 σ(2)受体亚型的亲和力。1-[4-(2-苯乙基)哌嗪-1-基]甲基-3-甲基-1H-吲哚 3b 对 σ(1)受体具有高亲和力，而三种化合物，1-[3-[4-(取代苯基)哌嗪-1-基]丙基]-1H-吲哚衍生物 4a-c 对 σ(2)受体具有高亲和力和选择性。对来自肝癌 (HUH7)、乳腺癌 (MCF7) 和结肠癌 (HCT-116) 癌细胞系的化合物进行了细胞毒性测试。化合物 1c (3-[4-(3,4-二氯苄基)哌嗪-1-基]甲基-1H-吲哚)对选定的癌细胞系表现出显著的细胞生长抑制活性。
