Design, synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents

被引：57

作者：

Han, Kailin ^{[1
,2
]}

Zhou, Yao ^{[1
,2
]}

Liu, Fengxi ^{[1
,2
]}

Guo, Qiannan ^{[1
,2
]}

Wang, Pengfei ^{[1
,2
]}

Yang, Yao ^{[1
,2
]}

Song, Binbin ^{[1
,2
]}

Liu, Wei ^{[3
]}

Yao, Qingwei ^{[4
]}

Teng, Yuou ^{[1
,2
]}

Yu, Peng ^{[1
,2
]}

机构：

[1] Tianjin Univ Sci & Technol, Coll Biotechnol, Key Lab Ind Microbiol, Minist Educ, Tianjin 300457, Peoples R China

[2] Tianjin Univ Sci & Technol, Coll Biotechnol, Tianjin Key Lab Ind Microbiol, Tianjin 300457, Peoples R China

[3] Tianjin Univ Sci & Technol, Coll Sci, Tianjin 300457, Peoples R China

[4] Chemo Dynam Inc, Sayreville, NJ 08872 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 02期

基金：

中国国家自然科学基金; 对外科技合作项目（国际科技项目）;

关键词：

Isatin derivatives; In vitro cytotoxicity; Antitumor activity; ISATIN SULFONAMIDE ANALOGS; INHIBITOR; CASPASE-3; CONDENSATION; SU11248; POTENT; SERIES;

D O I：

10.1016/j.bmcl.2013.12.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Forty four di-or trisubstituted novel isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by H-1 NMR and C-13 NMR as well as LC-MS. The anticancer activity of these new isatin derivatives against three human tumor cell lines, K562, HepG2 and HT-29, were evaluated by MTT assay in vitro. SAR studies suggested that the combination of 1-benzyl and 5-[trans-2-(methoxycarbonyl)ethen-1-yl] substitution greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 as present in the parent ring is required to such a potency. This study leads to the identification of two highly active molecules, compounds 2h (IC50 = 3 nM) and 2k (IC50 = 6 nM), against human leukemia K562 cells. (C) 2014 Published by Elsevier Ltd.

引用

页码：591 / 594

页数：4

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