异海松酰基噻吩类磺酰胺的制备及其抗肿瘤活性研究  

Synthesis and Antitumor Activity of Isopimaric Thiophene Sulfonamides Derivatives

作　　者：卢言菊[1,2] 赵振东[1,2] 毕良武[1,2] 陈玉湘[1,2] 王婧[1,2] 古研[1,2] LU Yanju;ZHAO Zhendong;BI Liangwu;CHEN Yuxiang;WANG Jing;GU Yan(Institute of Chemical Industry of Forest Products,CAF,National Engineering Lab.for Biomass Chemical Utilization,Key Lab.of Chemical Engineering of Forest Products,National Forestry and Grassland Administration,Key Lab.of Biomass Energy and Material,Jiangsu Province,Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources,Nanjing 210042,China;Research Institute of Forestry New Technology,CAF,Beijing 100091,China)

机构地区：[1]中国林业科学研究院林产化学工业研究所,生物质化学利用国家工程实验室,国家林业和草原局林产化学工程重点实验室,江苏省生物质能源与材料重点实验室,江苏省林业资源高效加工利用协同创新中心,江苏南京210042 [2]中国林业科学研究院林业新技术研究所,北京100091

出　　处：《林产化学与工业》2020年第5期57-62,共6页Chemistry and Industry of Forest Products

基　　金：国家自然科学基金资助项目(31700504);江苏省生物质能源与材料重点实验室基本科研业务费(JSBEM-201808)。

摘　　要：以异海松酸为原料,酰氯化制得异海松酸酰氯,然后异海松酸酰氯再与对苯二胺连接的噻吩类磺酰胺发生胺解反应,合成得到4个未见报道的异海松酰基噻吩类磺酰胺:异海松酰基-4-溴-2,5-二氯噻吩-3-磺酰胺(5a)、异海松酰基-5-溴噻吩-2-磺酰胺(5b)、异海松酰基-5-氯-4-硝基噻吩-2-磺酰胺(5c)、异海松酰基-噻吩-2-磺酰胺(5d)。对合成的化合物的结构用FT-IR、1 H NMR、13 C NMR和ESI-MS进行确证,并采用噻唑蓝(MTT)法测定了目标化合物对4种肿瘤细胞的抑制活性。研究结果表明:浓度100μmol/L时,化合物5b对Hela、MDA-MB-231及Hep G2的肿瘤细胞增殖抑制率均超过90%,其抑制率分别为91.36%、94.06%和92.26%,而对PC-3的肿瘤细胞抑制率为86.93%,也接近90%,说明化合物5b具有良好的抗肿瘤活性。通过IC 50值的测定进一步得出化合物5b的抑制效果优于阳性对照物临床上应用较广的抗癌剂5-氟尿嘧啶(5-FU)。Isopimaric chloride(compound 2)was synthesized by using isopimaric acid as raw material.Then four new isopimaric thiophene sulfonamides derivatives:isopimaric acid acyl-4-bromo-2,5-dichlorothiophene-3-sulfonamide(5a),isopimaric acid acyl-5-bromothiophene-2-sulfonamide(5b),isopimaric acid acyl-5-chloro-4-nitro-sulfonamide(5c),and isopimaric acid acyl-thiophene-2-sulfonamide(5d)were prepared by aminolysis reaction from compound 2 and thiophere sulfonamides which were connected with p-phenylenediamine.The structures of the compound were confirmed by FT-IR,1 H NMR,13 C NMR,and ESI-MS.In addition,the cell proliferation inhibition assay(MTT method)was used to study the in vitro inhibitory activity of 5a-5d on four human tumor cells.The results showed that compound 5b had inhibition rates of 91.36%,94.06%and 92.26%against Hela,MDA-MB-231 and Hep G-2 at the concentration of 100μmol/L,besides,the inhibition rate against PC-3 was 86.93%,which was close to 90%,indicating that compound 5b had good antitumor activity.Through the determination of IC 50 value,it was further concluded that the inhibition effect of compound 5b was better than that of 5-fluorouracil(5-FU),a widely used anticancer agent in clinic.

关 键 词：异海松酸 噻吩 磺酰胺 合成 表征 生物活性 

分 类 号：TQ351[化学工程]