TY - JOUR
T1 - Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates
AU - Xu, Jimin
AU - Pachón-Ibáñez, María Eugenia
AU - Cebrero-Cangueiro, Tania
AU - Chen, Haiying
AU - Sánchez-Céspedes, Javier
AU - Zhou, Jia
N1 - Funding Information:
This work was supported by UTMB Technology Commercialization Program, and Sanofi Innovation Awards (iAwards), John Sealy Memorial Endowment Fund, and Institute for Translational Sciences (ITS) at UTMB, Plan Nacional de I + D + i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe” Operative program Intelligent Growth 20142020, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI15/00489) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018) Servicio Andaluz de Salud, Junta de Andalucía.
Funding Information:
This work was supported by UTMB Technology Commercialization Program, and Sanofi Innovation Awards (iAwards), John Sealy Memorial Endowment Fund, and Institute for Translational Sciences (ITS) at UTMB, Plan Nacional de I?+?D?+?i 2013-2016 and Instituto de Salud Carlos III, Subdirecci?n General de Redes y Centros de Investigaci?n Cooperativa, Ministerio de Econom?a, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund ?A way to achieve Europe?, Operative program Intelligent Growth 20142020, the Instituto de Salud Carlos III, Proyectos de Investigaci?n en Salud (PI15/00489) and Proyectos de Desarrollo Tecnol?gico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program ?Nicol?s Monardes? (C-0059-2018) Servicio Andaluz de Salud, Junta de Andaluc?a.
Funding Information:
This work was supported by UTMB Technology Commercialization Program , and Sanofi Innovation Awards (iAwards), John Sealy Memorial Endowment Fund , and Institute for Translational Sciences (ITS) at UTMB, Plan Nacional de I + D + i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 20142020, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud ( PI15/00489 ) and Proyectos de Desarrollo Tecnológico en Salud ( DTS17/00130 ), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT ), and the program “ Nicolás Monardes ” ( C-0059-2018 ) Servicio Andaluz de Salud, Junta de Andalucía.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Carbapenemase-producing Enterobacteriaceae (CPE) represents the most worrisome evolution of the antibiotic resistance crisis, which is almost resistant to most of available antibiotics. This situation is getting even worse particularly due to the recent emergence of colistin resistance. Herein, niclosamide, an FDA-approved traditional drug, and its novel O-alkylamino-tethered derivatives were discovered as new and potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Among these molecules, compound 10 (HJC0431) with 4-aminobutyl moiety showed the broad antibacterial activities, effective against 6 strains. In vitro checkerboard and time-kill course studies demonstrated the synergistic effects of the screened compounds with colistin against the corresponding strains with various degrees.
AB - Carbapenemase-producing Enterobacteriaceae (CPE) represents the most worrisome evolution of the antibiotic resistance crisis, which is almost resistant to most of available antibiotics. This situation is getting even worse particularly due to the recent emergence of colistin resistance. Herein, niclosamide, an FDA-approved traditional drug, and its novel O-alkylamino-tethered derivatives were discovered as new and potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Among these molecules, compound 10 (HJC0431) with 4-aminobutyl moiety showed the broad antibacterial activities, effective against 6 strains. In vitro checkerboard and time-kill course studies demonstrated the synergistic effects of the screened compounds with colistin against the corresponding strains with various degrees.
KW - Antibacterial agents
KW - Carbapenemase-producing Enterobacteriaceae
KW - Colistin resistance
KW - Niclosamide derivatives
KW - Synergistic effects
UR - http://www.scopus.com/inward/record.url?scp=85063877679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063877679&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2019.03.032
DO - 10.1016/j.bmcl.2019.03.032
M3 - Article
C2 - 30954430
AN - SCOPUS:85063877679
VL - 29
SP - 1399
EP - 1402
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 11
ER -