含1,3,4-噻二唑、硫醚、酰胺的1,3-二取代吲哚酮衍生物的设计、合成及抗肿瘤活性研究
收稿日期: 2018-03-29
修回日期: 2018-05-06
网络出版日期: 2018-06-06
基金资助
贵州省科技计划（No.20161055）、贵州省教育厅青年科技人才成长（No.KY[2017]115）和药用植物功效与利用国家重点实验室（No.FAMP201707K）资助项目.
Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives
Received date: 2018-03-29
Revised date: 2018-05-06
Online published: 2018-06-06
Supported by
Project supported by the Guizhou Science Technology Program (No. 20161055), the Young Talents Scientific Research Foundation of Guizhou Education Department (No. KY[2017]115), and the State Key Laboratory of Functions and Applications of Medicinal Plants (No. FAMP201707K).
以吲哚酮为先导化合物，设计合成了20个含1，3，4-噻二唑、硫醚、酰胺的1，3-二取代吲哚酮衍生物.采用噻唑蓝（MTT）试验法测试目标化合物的体外抑制肿瘤细胞生长活性，测试结果表明：部分目标化合物对人肝癌细胞HepG2、人转移胰腺癌细胞AsPc-1和人宫颈癌细胞Hela表现出良好的抑制活性；其中N-（5-（（2-氟苄基）硫基）-1，3，4-噻二唑-2-基）-3-（2-氧代-3-（（对-甲苯基）亚氨基）二氢吲哚-1-基）丙酰胺（6l）和N-（5-（（2-甲基苄基）硫基）-1，3，4-噻二唑-2-基）-3-（2-氧代-3-（（对甲苯基）亚氨基）二氢吲哚-1-基）丙酰胺（6p）对HePG2、AsPc-1和Hela细胞的IC50分别为（11.47±0.01）、（2.43±0.05）和（1.91±0.06）μmol/L；（14.32±0.01）、（1.61±0.04）和（2.77±0.05）μmol/L，其抑制活性均优于阳性对照吉非替尼[（16.41±0.05）、（5.19±0.02）和（7.89±0.05）μmol/L].
田坤 , 孟娇 , 甘宜远 , 李小琴 , 巫受群 , 陈洁 , 李文 , 漆亚云 , 胡伟男 , 王贞超 , 欧阳贵平 . 含1,3,4-噻二唑、硫醚、酰胺的1,3-二取代吲哚酮衍生物的设计、合成及抗肿瘤活性研究[J]. 有机化学, 2018 , 38(10) : 2657 -2665 . DOI: 10.6023/cjoc201803051
A series of novel 1,3-disubstituted-indol-2-one derivatives containing 1,3,4-thiadiazole, thioether and amide moiety were designed and synthesized based on 2,3-dioxindole (isatin). The inhibition activities of all the target compounds against several cancer cell lines were evaluated via thiazolyl blue tetrazolium bromide (MTT) assay method. The preliminary bioassay results indicated that all of the title compounds exhibited a certain antitumor activity in vitro against human liver cancer cell line (HepG2), human transfer of pancreatic cancer cell line (AsPc-1) and human cervical cancer cell line (Hela). The IC50s values of N-(5-((2-fluorobenzyl)thio)-1,3,4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)propanamide (6l) [(11.47±0.01), (2.43±0.05), (1.91±0.06) μmol/L, respectively] and N-(5-((2-methylbenzyl)thio)-1,3,4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)-propanamide (6p) [(14.32±0.01), (1.61±0.04), (2.77±0.05) μmol/L, respectively] against HepG2, AsPc-1 and Hela cell lines were lower than that of control gefitinib [(16.41±0.05), (5.19±0.02), (7.89±0.05) μmol/L, respecti-vely].
Key words： indol-2-one derivatives; thiadiazole; thioether; amide; antitumor activity
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