5-取代-2-羟甲基苯酚衍生物的合成及体外抗肿瘤活性研究  

Synthesis and in Vitro Antitumor activities of 5-Substituted-2-(Hydroxymethyl) phenol Derivatives

作　　者：朱周静 仝红娟 张彦民 刘斌[1] Zhu Zhoujing;Tong Hongjuan;Zhang Yanmin;Liu Bin(School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xianyang,712046;Collaborative Innovation Center of Green Manufacturing Technology for Traditional Chinese Medicine in Shaanxi Province,Xianyang,712046)

机构地区：[1]陕西国际商贸学院医药学院,咸阳712046 [2]陕西省中药绿色制造技术协同创新中心,咸阳712046

出　　处：《化学通报》2021年第9期942-946,共5页Chemistry

基　　金：陕西省自然科学基金项目(2021JM-540);陕西省自然科学基金项目(2021JQ-885);陕西国际商贸学院“中药药效物质研究”创新团队项目(SSY18TD01);陕西国际商贸学院一流专业建设项目资助。

摘　　要：以2-羟基-4-甲基苯甲酸为原料,经过丙酮叉保护、NBS溴代制得中间体7-(溴甲基)-2,2-二甲基-4H-苯并[d][1,3]二氧六环-4-酮(4),再分别与两种杂环仲胺发生N-烷基化反应制得化合物5a、5b,最后经过四氢铝锂还原得到目标化合物1a、1b,其结构经^(1)H NMR、^(13)C NMR和ESI-MS进行确证。此外,采用MTT法测试了1a、1b对HepG2、HeLa、MCF-7、A5494四种肿瘤细胞以及正常宫颈上皮细胞HUCEC的体外抑制活性。结果表明,目标化合物1a、1b对HeLa细胞展现出明显的抑制作用,IC50分别为18.4和10.6μmol/L,而对正常的HUCEC细胞没有抑制活性。这些结果有望为进一步开发具有抗肿瘤活性的2-羟甲基苯酚衍生物提供参考。7-(Bromomethyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one(4) was synthesized via acetonide protection and bromination reaction by NBS using 2-hydroxy-4-methylbenzoic acid as raw material, which was reacted with heterocyclic secondary amine to produce compounds 5 a, 5 b. Subsequently, 5 a, 5 b were reduced by LiAlH4 to obtain target compounds 1 a, 1 b. The structures of 1 a, 1 b were characterized by ^(1)H NMR, ^(13)C NMR and ESI-MS. The target compounds 1 a, 1 b were tested for their in vitro antitumor activity against HepG2,HeLa, MCF-7,A549 by MTT assay. They exhibite significant inhibitory effects on HeLa cells with IC50 of 18.4 and 10.6 μmol·L-1, respectively. Moreover, they showed no significant toxicity to normal HUCEC cells. These results may provide reference for the further development of 2-hydroxymethyl phenol derivatives as antitumor agents.

关 键 词：5-取代-2-羟甲基苯酚 N-烷基化反应 抗肿瘤活性 

分 类 号：TQ463[化学工程—制药化工]