Discovery of a 1,2-bis(3-indolyl)ethane that selectively inhibits the pyruvate kinase of methicillin-resistant Staphylococcus aureus over human isoforms

被引：17
作者：
Zoraghi, Roya [1 ]
Campbell, Sara [3 ]
Kim, Catrina [3 ]
Dullaghan, Edie M. [3 ]
Blair, Lachlan M. [4 ]
Gillard, Rachel M. [4 ]
Reiner, Neil E. [1 ,2 ]
Sperry, Jonathan [4 ]
机构：
[1] Univ British Columbia, Dept Med, Div Infect Dis, Vancouver, BC V5Z 3J5, Canada
[2] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 3J5, Canada
[3] Ctr Drug Res & Dev, Vancouver, BC, Canada
[4] Univ Auckland, Sch Chem Sci, Auckland 1, New Zealand
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 21期
关键词：
Pyruvate kinase; MRSA; Antibacterial; Indole; OPTIMIZATION;
D O I：
10.1016/j.bmcl.2014.09.010
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Methicillin-resistant Staphylococcus aureus pyruvate kinase (MRSA PK) has recently been identified as a target for development of novel antibacterial agents. Testing a series of 1,2-bis(3-indolyl)ethanes against MRSA PK has led to the discovery of a potent inhibitor that is selective over human isoforms. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5059 / 5062
页数：4
相关论文
共 12 条
[1]   Resistance to antibiotics: Are we in the post-antibiotic era? [J].
Alanis, AJ .
ARCHIVES OF MEDICAL RESEARCH, 2005, 36 (06) :697-705
[2]  
Blair L. M., 2013, J SYNLETT, P1931
[3]   Mapping the Protein Interaction Network in Methicillin-Resistant Staphylococcus aureus [J].
Cherkasov, Artem ;
Hsing, Michael ;
Zoraghi, Roya ;
Foster, Leonard J. ;
See, Raymond H. ;
Stoynov, Nikolay ;
Jiang, Jihong ;
Kaur, Sukhbir ;
Lian, Tian ;
Jackson, Linda ;
Gong, Huansheng ;
Swayze, Rick ;
Amandoron, Emily ;
Hormozdiari, Farhad ;
Dao, Phuong ;
Sahinalp, Cenk ;
Santos-Filho, Osvaldo ;
Axerio-Cilies, Peter ;
Byler, Kendall ;
McMaster, William R. ;
Brunham, Robert C. ;
Finlay, B. Brett ;
Reiner, Neil E. .
JOURNAL OF PROTEOME RESEARCH, 2011, 10 (03) :1139-1150
[4]   Increased mortality associated with meticillin-resistant Staphylococcus aureus (MRSA) infection in the Intensive Care Unit: results from the EPIC II study [J].
Hanberger, Hakan ;
Walther, Sten ;
Leone, Marc ;
Barie, Philip S. ;
Rello, Jordi ;
Lipman, Jeffrey ;
Marshall, John C. ;
Anzueto, Antonio ;
Sakr, Yasser ;
Pickkers, Peter ;
Felleiter, Peter ;
Engoren, Milo ;
Vincent, Jean-Louis .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2011, 38 (04) :331-335
[5]   Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections [J].
Kumar, Nag S. ;
Dullaghan, Edie M. ;
Finlay, B. Brett ;
Gong, Huansheng ;
Reiner, Neil E. ;
Selvam, J. Jon Paul ;
Thorson, Lisa M. ;
Campbell, Sara ;
Vitko, Nicholas ;
Richardson, Anthony R. ;
Zoraghi, Roya ;
Young, Robert N. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (05) :1708-1725
[6]   Optimization and structure-activity relationships of a series of potent inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as novel antimicrobial agents [J].
Kumar, Nag S. ;
Amandoron, Emily A. ;
Cherkasov, Artem ;
Finlay, B. Brett ;
Gong, Huansheng ;
Jackson, Linda ;
Kaur, Sukhbir ;
Lian, Tian ;
Moreau, Anne ;
Labriere, Christophe ;
Reiner, Neil E. ;
See, Raymond H. ;
Strynadka, Natalie C. ;
Thorson, Lisa ;
Wong, Edwin W. Y. ;
Worrall, Liam ;
Zoraghi, Roya ;
Young, Robert N. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (24) :7069-7082
[7]   Platforms for antibiotic discovery [J].
Lewis, Kim .
NATURE REVIEWS DRUG DISCOVERY, 2013, 12 (05) :371-387
[8]   Empirical antibacterial drug discovery - Foundation in natural products [J].
Singh, SB ;
Barrett, JF .
BIOCHEMICAL PHARMACOLOGY, 2006, 71 (07) :1006-1015
[9]   The allosteric regulation of pyruvate kinase - A site-directed mutagenesis study [J].
Valentin, G ;
Chiarelli, L ;
Fortin, R ;
Speranza, ML ;
Galizzi, A ;
Mattevi, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (24) :18145-18152
[10]  
Watts J. L., 2008, CLIN LAB STAND I, V28, pM31
12