α,α'-双(对二甲氨亚苄基)环烷酮的合成及其体外光动力抗肿瘤活性  

Synthesis of α,α'-bis(p-methylaminobenzyl) cycloalkanone and its phototoxicity in vitro

作　　者：屈小芳 曹亚萍 吴庆 胡庆红 袁泽利 Qu Xiaofang, Cao Yaping, Wu Qing, Hu Qinghong, Yuan Zeli(Department of Inorganic Chemistry, School of Pharmacy, Zunyi Medical University, Guizhou Zunyi 563099, Chin)

机构地区：[1]遵义医学院药学院无机化学教研室,贵州遵义563099

出　　处：《遵义医学院学报》2018年第1期15-19,25,共6页Journal of Zunyi Medical University

基　　金：国家自然科学基金项目(NO:81360471;81660975);贵州省国际合作项目(NO:[2012]7036)

摘　　要：目的开发具有光动力治疗作用的先导化合物,并探寻其体外光动力抗肿瘤活性。方法将对二甲氨基苯甲醛与环烷酮通过Cross-Aldol缩合生成α,α'-双(对二甲氨亚苄基)环烷酮1a^1c,利用~1H NMR、^(13)C NMR、高分辨质谱及FTIR谱对其进行结构表征,并用X射线单晶衍射对1a进行结构表征。利用紫外-可见分光光度计及荧光分光光度计考察其光谱性能。采用噻唑蓝(MTT)法考察所得先导化合物1a^1c对A549(人源肺腺癌细胞)和HepG2(人源肝癌细胞)的暗毒性和光毒性。结果成功制备得到了化合物1a^1c。化合物1a的晶体结构属于单斜晶系(Monoclinic),P2_1/c空间群,晶胞参数为α=7.489(2)A,b=19.945(6)A,c=12.403(3)A,α=90°,β=96.965(10)°,γ=90°。V=1 839.0(9)~3,Dc=1.201Mg/m^3,μ=0.074 mm^(-1),Z=4,F(000)=712.0,R1=0.065 5,wR_2=0.224 0,S=0.902。化合物1a-1c对A549和HepG2暗毒性和光毒性的结果表明:化合物1a对两株受试细胞株表现出了较强的光毒性,光毒性IC_(50)值分别为5.48μmol/L和10.50μmol/L。结论1a的体外光毒活性优于1b、1c,可作为光动力治疗先导物进一步研究。Objective To develop lead compounds with photodynamic therapy and explore their phototoxicity in vitro. Methods α,α＇bis（p-methylaminobenzyl） cycloalkanone 1 a^1 c were obtained by the Cross-Aldol condensation reaction of p-dimethylaminobenzaldehyde with cycloalkanones, then their structures were characterized by modern analytical techniques such as ~1 H NMR,^（13）C NMR,FT-IR. Meanwhile,the crystal structure ofα,α＇-bis（p-methylaminobenzyl） cyclobutanone compound la was measured by X-ray single crystal diffraction. The photochemical properties of these compounds were studied by UV-vis and fluorescence spectroscopy.The phototoxicity of compounds 1 a^1 c were investigated by thiazolyl blue tetrazolium bromide（MTT）method in human lung adenocarcinoma cells（ A549） and human hepatoma cells（ HepG2）. Results The compounds 1a^1c were prepared successfully. The crystal structure of compound la belongs to monoclinic, space group P2_1/c with the following crystallographic parameters： a=7.489（ 2）,b=19. 945（ 6）, c=12. 403（ 3）,α=90°,β =96.965（ 10）°,γ=90°.V=1 839.0（9）~3,Dc=1.201 g/cm^3,μ=0.074 mm^（-1）,Z=4,F（ 000）=712.0,R_1=0.065 5,wR_2=0.224 0,S=0.902. The results of dark toxicity and phototoxicity of compounds 1a-1c to A549 and HepG2 showed that the compound la had strong phototoxicity to two cell lines,and the IC_（50） values were 5.48 and 10.50 μmol/L,respectively. Conclusion The antitumor activity of the new compound la is better than that of lb and lc,and it＇s worthy of further study as a potential photodynamic therapy drug.

关 键 词：α α'-双(对二甲氨亚苄基)环烷酮 晶体结构 光毒性 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] O622[医药卫生—药学]