苯并咪唑和苯并噻唑类衍生物的合成及其sirtuins抑制活性评价

Synthesis of benzimidazole and benzothiazole derivatives as a sirtuins 2 inhibitor

摘要: 设计合成新型结构sirtuins抑制剂并评价其对SIRT1~SIRT3的抑制活性。基于已报道的sirtuins抑制剂结构和药效团特征，设计了一系列苯并咪唑和苯并噻唑类化合物。以乙基黄原酸钾为起始原料，经3步反应合成了16个未见文献报道的目标化合物，目标化合物的结构经¹H NMR、HR-MS确证。对目标化合物进行SIRT1~SIRT3的抑制活性评价，其中苯并咪唑类化合物对SIRT2具有选择性的抑制活性。

Abstract: A series of novel benzimidazole and benzothiazole derivatives were designed and synthesized as inhibitors of SIRT1-SIRT3. The target compounds were synthesized from potassium O-ethyldithiocarbonate through a three-step route. The structures of the obtained compounds were elucidated by ¹H NMR and HR-MS. Of all compounds, six showed potent SIRT2-inhibitory activities with IC₅₀ values ranging from 2.8 to 21.2 μmol·L^-1. Among them, compound 10c displayed the most potent SIRT2-inhibitory activities (IC₅₀ = 2.8 μmol·L^-1), with more than 35-fold selectivity over SIRT1 and SIRT3 (IC₅₀>100 μmol·L^-1).