新型二苯甲酮哌嗪类化合物的合成及对H_2O_2损伤的EA.hy 926细胞的保护作用  

Synthesis of novel benzophenone piperazine compounds and their protective activities against H_2O_2 induced injury in EA.hy 926 cells

作　　者：孔德朋 冯秀娥[1] 班树荣[1] 李青山[1] 

机构地区：[1]山西医科大学药学院,山西太原030001

出　　处：《中国药物化学杂志》2017年第3期194-199,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家高技术研究发展计划项目("863"计划;2013AA092903);国家自然科学基金项目(81473100);山西医科大学博士启动基金项目(B03201213);2014年度山西省煤基重点科技攻关项目(MJH2014-14);山西省自然科学基金项目(20150111047)

摘　　要：目的合成系列新型氟代/溴代甲氧基二苯甲酮哌嗪类化合物,测定其对H_2O_2损伤的EA.hy 926细胞的保护作用,并初步探讨其构效关系。方法以2-甲基-5-氟苯甲酰氯或2-甲基-5-溴苯甲酸为起始原料,经过傅克酰化、自由基取代以及亲核取代等关键反应合成目标化合物。采用MTT法考察了目标化合物对H_2O_2损伤的EA.hy 926细胞的保护活性。结果与结论合成了12个未见文献报道的新化合物;目标化合物的结构经MS、~1H-NMR谱确证。体外活性筛选结果表明,溴原子取代的目标化合物11a、11b、11d^11f均具有较高的细胞保护活性,且优于阳性对照药槲皮素,其EC50值为4.0~7.4μmol·L^(-1)。Twelve new halogenated （bromo- and fuloro-） methoxyl benzophenone piperazine compounds were prepared via following key reactions：Friedel-Crafts acylation, radical-substitution and nucleophilic substitution starting from 5-fluoro-2-methyl benzoylchloride or 5-bromo-2-methylbenzoic acid. The structures of the target compounds were confirmed by MS, 1H-NMR and other analytical methods. Additionally, the pro- tective effects of the target compounds against H202 induced injury in EA. hy 926 cells were evaluated by MTT assay. Preliminary in vitro results showed that bromo-substituted target compounds lla, llb ,lid -llf exhibited protective potency at micromolar level, and were superior to the positive control quercetin, and their EC50 values was between 4. 0 μmol-L-1 and 7.4 μmol. L-1.

关 键 词：卤代甲氧基二苯甲酮 哌嗪 EA.hy 926细胞 保护作用 MTT法 

分 类 号：R914[医药卫生—药物化学]