溴代甲氧基二苯甲酮咪唑类化合物的合成及对过氧化氢致EA. hy 926细胞损伤的保护作用

本文旨在引入咪唑环,对溴代甲氧基二苯甲酮类化合物进行结构衍生,以发现对血管内皮细胞具有更高保护活性的化合物。通过以2-甲基-5-溴-苯甲酸为起始原料,经过酰氯化、傅克酰化、溴代、与N-溴代丁二酰亚胺(NBS)自由基取代及与取代咪唑的亲核取代等多步反应,合成了8个新型溴代甲氧基二苯甲酮咪唑类化合物。目标化合物的结构均经质谱(MS)、核磁共振波谱仪(NMR)和高分辨质谱(HRMS)进行确证。并采用噻唑蓝(MTT)法考察了目标化合物对过氧化氢损伤的EA.hy 926细胞的保护活性,结果表明,目标化合物6a、6g、6h具有显著的细胞保护活性,其半抑制浓度(EC50)分别为1.9、4.0和3.2μmol/L,优于阳性对照槲皮素(EC_(50)为18μmol/L),表明该类化合物在心血管疾病的治疗方面有潜在的应用前景。

Synthesis of Bromo-Methoxyl Benzophenone Imidazole Compounds and Their Protective Activities Against Hydrogen Peroxide Induced Injury in EA.hy 926 Cells

To introduce the imidazole ring to the bromo-methoxyl benzophenone structures and find the target compounds with high protective activity on vacular endothelium cells, eight novel bromo-methoxyl benzophenone imidazole compounds were synthesized using 5-bromo-2-methylbenzoic acid as starting material via following reactions:acylating chlorination, Friedel acylation, bromination, radical substitution with N-bromosuccinimide(NBS) and nucleophilic substitution with substituted imidazoles. The structures of the target compounds were confirmed by proton and carbon nuclear magnetic resonance spectroscopy(¹H and ¹³C NMR) and high resolution mass spectrometry(HRMS). Additionally, the protective effects of the target compounds against H₂O₂-induced EA.hy 926 cells injury were evaluated by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay and their structure-activity relationships were also preliminarily discussed. The in vitro results show that target compounds 6a, 6g and 6h exhibit significant cytoprotective activities and their half maximal inhibitory concentration(EC₅₀) values are 1.9, 4.0 and 3.2 μmol/L, respectively, superior to the positive control Quercetin(EC₅₀≈18 μmol/L). These results also suggest the potential application prospect of target compounds in the treatment of cardiovascular diseases.