Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates

Jimin Xu; María Eugenia Pachón-Ibáñez; Tania Cebrero-Cangueiro; Haiying Chen; Javier Sánchez-Céspedes; Jia Zhou

doi:10.1016/j.bmcl.2019.03.032

Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates

Jimin Xu, María Eugenia Pachón-Ibáñez, Tania Cebrero-Cangueiro, Haiying Chen, Javier Sánchez-Céspedes, Jia Zhou

Pharmacology & Toxicology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1399-1402
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2019.03.032
State	Published - Jun 1 2019

Keywords

Antibacterial agents
Carbapenemase-producing Enterobacteriaceae
Colistin resistance
Niclosamide derivatives
Synergistic effects

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Xu, J., Pachón-Ibáñez, M. E., Cebrero-Cangueiro, T., Chen, H., Sánchez-Céspedes, J., & Zhou, J. (2019). Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Bioorganic and Medicinal Chemistry Letters, 29(11), 1399-1402. https://doi.org/10.1016/j.bmcl.2019.03.032

Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. / Xu, Jimin; Pachón-Ibáñez, María Eugenia; Cebrero-Cangueiro, Tania; Chen, Haiying; Sánchez-Céspedes, Javier; Zhou, Jia.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 29, No. 11, 01.06.2019, p. 1399-1402.

Research output: Contribution to journal › Article › peer-review

Xu, J, Pachón-Ibáñez, ME, Cebrero-Cangueiro, T, Chen, H, Sánchez-Céspedes, J & Zhou, J 2019, 'Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates', Bioorganic and Medicinal Chemistry Letters, vol. 29, no. 11, pp. 1399-1402. https://doi.org/10.1016/j.bmcl.2019.03.032

Xu J, Pachón-Ibáñez ME, Cebrero-Cangueiro T, Chen H, Sánchez-Céspedes J, Zhou J. Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Bioorganic and Medicinal Chemistry Letters. 2019 Jun 1;29(11):1399-1402. https://doi.org/10.1016/j.bmcl.2019.03.032

Xu, Jimin ; Pachón-Ibáñez, María Eugenia ; Cebrero-Cangueiro, Tania ; Chen, Haiying ; Sánchez-Céspedes, Javier ; Zhou, Jia. / Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. In: Bioorganic and Medicinal Chemistry Letters. 2019 ; Vol. 29, No. 11. pp. 1399-1402.

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abstract = "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.",

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AU - Sánchez-Céspedes, Javier

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