Design, synthesis and preliminary bioactivity studies of indomethacin derivatives as Bcl-2/Mcl-1 dual inhibitors

被引：18

作者：

Chen, Chen ^{[1
]}

Nie, Yiming ^{[1
]}

Xu, Guangsen ^{[1
]}

Yang, Xinying ^{[1
]}

Fang, Hao ^{[1
]}

Hou, Xuben ^{[1
]}

机构：

[1] Shandong Univ, Dept Med Chem, Key Lab Chem Biol, Minist Educ,Sch Pharmaceut Sci, 44 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2019年 / 27卷 / 13期

基金：

中国国家自然科学基金;

关键词：

Apoptosis; Anticancer; Bcl-2/Mcl-1 dual inhibitor; Indomethacin derivatives; MCL-1; INHIBITORS; BCL-2; PROTEINS; RESISTANCE; ABT-199; CELL;

D O I：

10.1016/j.bmc.2019.05.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bcl-2 family proteins, which divides into pro-apoptosis proteins and anti-apoptosis proteins, are involved in cell apoptosis progression. As numerous studies illustrated, targeting Bcl-2 family proteins is more and more attractive and practicable to cancer treatment. In this work, we designed and synthesized a series of indomethacin derivatives as new inhibitors for Bcl-2 family proteins. Our results of binding assay to Bcl-2 proteins, MTT assay and apoptotic assay indicated that some compounds had potent binding affinity to Bcl-2/Mcl-1 but not Bcl-X-L. Furthermore, compound 8j showed improved anti-proliferative activity than known Bcl-2 inhibitor WL-276.

引用

页码：2771 / 2783

页数：13

共 24 条

[1] A New View of the Lethal Apoptotic Pore [J].

Basanez, Gorka ;

Soane, Lucian ;

Hardwick, J. Marie .

PLOS BIOLOGY, 2012, 10 (09)

[2] ABT-199: Taking Dead Aim at BCL-2 [J].

Davids, Matthew S. ;

Letai, Anthony .

CANCER CELL, 2013, 23 (02) :139-141

[3] Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3β activity and associates with poor prognosis in human breast cancer [J].

Ding, Qingqing ;

He, Xianghuo ;

Xia, Weiya ;

Hsu, Jung-Mao ;

Chen, Chun-Te ;

Li, Long-Yuan ;

Lee, Dung-Fang ;

Yang, Jer-Yen ;

Xie, Xiaoming ;

Liu, Jaw-Ching ;

Hung, Mien-Chie .

CANCER RESEARCH, 2007, 67 (10) :4564-4571

[4] Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy [J].

Fulda, S. ;

Debatin, K. -M .

ONCOGENE, 2006, 25 (34) :4798-4811

[5] Targeting MCL-1/BCL-XL Forestalls the Acquisition of Resistance to ABT-199 in Acute Myeloid Leukemia [J].

Lin, Kevin H. ;

Winter, Peter S. ;

Xie, Abigail ;

Roth, Cullen ;

Martz, Colin A. ;

Stein, Elizabeth M. ;

Anderson, Grace R. ;

Tingley, Jennifer P. ;

Wood, Kris C. .

SCIENTIFIC REPORTS, 2016, 6

[6] Maximizing cellulosic ethanol potentials by minimizing wastewater generation and energy consumption: Competing with corn ethanol [J].

Liu, Gang ;

Bao, Jie .

BIORESOURCE TECHNOLOGY, 2017, 245 :18-26

[7] ANALYTICAL SOLUTIONS FOR WATER-GAS FLOW THROUGH 3D ROCK FRACTURE NETWORKS SUBJECTED TO TRIAXIAL STRESSES [J].

Liu, Richeng ;

Li, Bo ;

Jing, Hongwen ;

Wei, Wei .

FRACTALS-COMPLEX GEOMETRY PATTERNS AND SCALING IN NATURE AND SOCIETY, 2018, 26 (03)

[8] Design, synthesis and preliminary biological evaluation of indole-3-carboxylic acid-based skeleton of Bcl-2/Mcl-1 dual inhibitors [J].

Liu, Tingting ;

Wan, Yichao ;

Liu, Renshuai ;

Ma, Lin ;

Li, Minyong ;

Fang, Hao .

BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (06) :1939-1948

[9] Programmed anuclear cell death delimits platelet life span [J].

Mason, Kylie D. ;

Carpinelli, Marina R. ;

Fletcher, Jamie I. ;

Collinge, Janelle E. ;

Hilton, Adrienne A. ;

Ellis, Sarah ;

Kelly, Priscilla N. ;

Ekert, Paul G. ;

Metcalf, Donald ;

Roberts, Andrew W. ;

Huang, David C. S. ;

Kile, Benjamin T. .

CELL, 2007, 128 (06) :1173-1186

[10] Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization [J].

Nikolovska-Coleska, Z ;

Wang, RX ;

Fang, XL ;

Pan, HG ;

Tomita, Y ;

Li, P ;

Roller, PP ;

Krajewski, K ;

Saito, NG ;

Stuckey, JA ;

Wang, SM .

ANALYTICAL BIOCHEMISTRY, 2004, 332 (02) :261-273

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