Citation: 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]. Chinese Journal of Organic Chemistry, ;2018, 38(10): 2657-2665. doi: 10.6023/cjoc201803051 shu

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

Corresponding author: Wang Zhenchao, wzc.4884@163.com Ouyang Guiping, oygp710@163.com
Received Date: 29 March 2018
Revised Date: 6 May 2018
Available Online: 5 October 2018
Fund Project: the State Key Laboratory of Functions and Applications of Medicinal Plants FAMP201707Kthe Young Talents Scientific Research Foundation of Guizhou Education Department No. KY[2017]115Project 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)the Guizhou Science Technology Program 20161055

Figures(2)

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].
- indol-2-one derivatives,
- thiadiazole,
- thioether,
- amide,
- antitumor activity
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