Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives

doi:10.6023/cjoc201803051

Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (10): 2657-2665.DOI: 10.6023/cjoc201803051 Previous Articles Next Articles

Articles

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

田坤^a, 孟娇^b, 甘宜远^b, 李小琴^a, 巫受群^a, 陈洁^b, 李文^b, 漆亚云^b, 胡伟男^b, 王贞超^b,c, 欧阳贵平^a,b,c

a 贵州大学精细化工研究开发中心绿色农药与农业生物工程国家重点实验室培育基地教育部绿色农药与生物工程重点实验室贵阳 550025;
b 贵州大学药学院贵阳 550025;
c 贵州省合成药物工程实验室贵阳 550025

收稿日期:2018-03-29 修回日期:2018-05-06 发布日期:2018-06-06
通讯作者: 欧阳贵平,E-mail:oygp710@163.com;王贞超,E-mail:wzc.4884@163.com E-mail:oygp710@163.com;wzc.4884@163.com
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

Tian Kun^a, Meng Jiao^b, Gan Yiyuan^b, Li Xiaoqin^a, Wu Shouqun^a, Chen Jie^b, Li Wen^b, Qi Yayun^b, Hu Weinan^b, Wang Zhenchao^b,c, Ouyang Guiping^a,b,c

a State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research of Fine Chemicals, Guizhou University, Guiyang 550025;
b College of Pharmacy, Guizhou University, Guiyang 550025;
c Drug Synthetic Engineering Laboratory of Guizhou Province, Guiyang 550025

Received:2018-03-29 Revised:2018-05-06 Published:2018-06-06
Contact: 10.6023/cjoc201803051 E-mail:oygp710@163.com;wzc.4884@163.com
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).

1. Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives.PDF(2514KB)

Abstract

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

Cite this article

Tian Kun, Meng Jiao, Gan Yiyuan, Li Xiaoqin, Wu Shouqun, Chen Jie, Li Wen, Qi Yayun, Hu Weinan, Wang Zhenchao, Ouyang Guiping. Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives[J]. Chin. J. Org. Chem., 2018, 38(10): 2657-2665.

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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

Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives

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