Design, synthesis and biological evaluation of 3-aryl-rhodanine benzoic acids as anti-apoptotic protein Bcl-2 inhibitors

被引：23
作者：
Fu, Huansheng [1 ]
Hou, Xuben [1 ]
Wang, Lei [1 ]
Dun, Yanyan [1 ]
Yang, Xinying [1 ]
Fang, Hao [1 ]
机构：
[1] Shandong Univ, Dept Med Chem, Key Lab Chem Biol, Minist Educ,Sch Pharm, Jinan 250012, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 22期
关键词：
Apoptosis; Bcl-2; Inhibitor; Rhodanine; SMALL-MOLECULE INHIBITORS; CELL LYMPHOMA 2; OBATOCLAX MESYLATE; DERIVATIVES; FAMILY; RHODANINE; COMBINATION; NAVITOCLAX; DISCOVERY; TRIAL;
D O I：
10.1016/j.bmcl.2015.09.051
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new class of 3-aryl-rhodanine benzoic acid derivatives were designed, synthesized, and evaluated for their inhibition activities against anti-apoptotic Bcl-2 proteins. The potent compounds 33 and 41 bound to Bcl-2 with submicromolar K-i values and had selectivities to Bcl-2/Mcl-1 over Bcl-xL. In addition, they exhibited obvious antiproliferative activities in three human tumor cell lines (MDA-MB-231, K562 and PC-3). (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5265 / 5269
页数：5
相关论文
共 36 条
[1]   2H-chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents [J].
Azizmohammadi, Mohammad ;
Khoobi, Mehdi ;
Ramazani, Ali ;
Emami, Saeed ;
Zarrin, Abdolhossein ;
Firuzi, Omidreza ;
Miri, Ramin ;
Shafiee, Abbas .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 59 :15-22
[2]   Synthesis of a rhodanine-based compound library targeting Bcl-XL and Mcl-1 [J].
Bernardo, Paul H. ;
Sivaraman, Thirunavukkarasu ;
Wan, Kah-Fei ;
Xu, Jin ;
Krishnamoorthy, Janarthanan ;
Song, Chun Meng ;
Tian, Liming ;
Chin, Jasmine S. F. ;
Lim, Diane S. W. ;
Mok, Henry Y. K. ;
Yu, Victor C. ;
Tong, Joo Chuan ;
Chai, Christina L. L. .
PURE AND APPLIED CHEMISTRY, 2011, 83 (03) :723-731
[3]   Structural Insights into the Design of Small Molecule Inhibitors That Selectively Antagonize Mcl-1 [J].
Bernardo, Paul H. ;
Sivaraman, Thirunavukkarasu ;
Wan, Kah-Fei ;
Xu, Jin ;
Krishnamoorthy, Janarthanan ;
Song, Chun Meng ;
Tian, Liming ;
Chin, Jasmine S. F. ;
Lim, Diane S. W. ;
Mok, Henry Y. K. ;
Yu, Victor C. ;
Tong, Joo Chuan ;
Chai, Christina L. L. .
JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (05) :2314-2318
[4]  
Bose P., 2013, RES REP, V2, P12
[5]   SOME 3-SUBSTITUTED RHODANINES [J].
BROWN, FC ;
BRADSHER, CK ;
MORGAN, EC ;
TETENBAUM, M ;
WILDER, P .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1956, 78 (02) :384-388
[6]   Obatoclax Mesylate, a Pan-Bcl-2 Inhibitor, in Combination with Docetaxel in a Phase 1/2 Trial in Relapsed Non-Small-Cell Lung Cancer [J].
Chiappori, Alberto ;
Williams, Charles ;
Northfelt, Donald W. ;
Adams, John W. ;
Malik, Shakun ;
Edelman, Martin J. ;
Rosen, Peter ;
Van Echo, David A. ;
Berger, Mark S. ;
Haura, Eric B. .
JOURNAL OF THORACIC ONCOLOGY, 2014, 9 (01) :121-125
[7]   A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors [J].
Cleary, James M. ;
Lima, Caio Max S. Rocha ;
Hurwitz, Herbert I. ;
Montero, Alberto J. ;
Franklin, Catherine ;
Yang, Jianning ;
Graham, Alison ;
Busman, Todd ;
Mabry, Mack ;
Holen, Kyle ;
Shapiro, Geoffrey I. ;
Uronis, Hope .
INVESTIGATIONAL NEW DRUGS, 2014, 32 (05) :937-945
[8]   The BCL2 family: Regulators of the cellular life-or-death switch [J].
Cory, S ;
Adams, JM .
NATURE REVIEWS CANCER, 2002, 2 (09) :647-656
[9]   Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL [J].
Degterev, A ;
Lugovskoy, A ;
Cardone, M ;
Mulley, B ;
Wagner, G ;
Mitchison, T ;
Yuan, JY .
NATURE CELL BIOLOGY, 2001, 3 (02) :173-182
[10]   Design, synthesis and biological evaluation of saccharin-based N-hydroxybenzamides as histone deacetylases (HDACs) [J].
Fu, Huansheng ;
Han, Leiqiang ;
Hou, Xuben ;
Dun, Yanyan ;
Wang, Lei ;
Gong, Xiaowei ;
Fang, Hao .
BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (17) :5774-5781
1234