新型强效和选择性 σ 配体：评估其激动剂和拮抗剂特性。
Novel potent and selective σ ligands: evaluation of their agonist and antagonist properties.
机构信息
Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
出版信息
J Med Chem. 2011 May 26;54(10):3669-73. doi: 10.1021/jm200144j. Epub 2011 Apr 21.
Novel enantiomers and diastereoisomers structurally related to σ ligand (+)-MR200 were synthesized to improve σ(1)/σ(2) subtype selectivity. The selective σ(1) ligand (-)-8 showed an antagonist profile determined by phenytoin differential modulation of binding affinity in vitro, confirmed in vivo by an increase of κ opioid analgesia. The σ(2) ligand (-)-9 displayed agonist properties in an in vitro isolated organ bath assay and antiproliferative effects on LNCaP and PC3 prostate cancer cell lines.
为了提高 σ(1)/σ(2)亚型选择性，合成了与 σ 配体 (+)-MR200 在结构上相关的新型对映异构体和非对映异构体。选择性 σ(1)配体 (-)-8 通过苯妥英体外调节结合亲和力的差异表现出拮抗剂特征，在体内通过增加 κ 阿片样物质镇痛作用得到证实。 σ(2)配体 (-)-9 在离体器官浴实验中表现出激动剂特性，并对 LNCaP 和 PC3 前列腺癌细胞系具有抗增殖作用。
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