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6-Bromoindirubin-3'-oxime derivatives are highly active colistin adjuvants against Klebsiella pneumoniae.


ABSTRACT: Multidrug resistant (MDR) bacterial infections have become increasingly common, leading clinicians to rely on last-resort antibiotics such as colistin. However, the utility of colistin is becoming increasingly compromised as a result of increasing polymyxin resistance. Recently we discovered that derivatives of the eukaryotic kinase inhibitor meridianin D abrogate colistin resistance in several Gram-negative species. A subsequent screen of three commercial kinase inhibitor libraries led to the identification of several scaffolds that potentiate colistin activity, including 6-bromoindirubin-3'-oxime, which potently suppresses colistin resistance in Klebsiella pneumoniae. Herein we report the activity of a library of 6-bromoindirubin-3'-oxime analogs and identify four derivatives that show equal or increased colistin potentiation activity compared to the parent compound.

SUBMITTER: Li H 

PROVIDER: S-EPMC9945867 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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6-Bromoindirubin-3'-oxime derivatives are highly active colistin adjuvants against <i>Klebsiella pneumoniae</i>.

Li Haoting H   Mattingly Anne E AE   Smith Richard D RD   Melander Roberta J RJ   Ernst Robert K RK   Melander Christian C  

RSC medicinal chemistry 20221201 2


Multidrug resistant (MDR) bacterial infections have become increasingly common, leading clinicians to rely on last-resort antibiotics such as colistin. However, the utility of colistin is becoming increasingly compromised as a result of increasing polymyxin resistance. Recently we discovered that derivatives of the eukaryotic kinase inhibitor meridianin D abrogate colistin resistance in several Gram-negative species. A subsequent screen of three commercial kinase inhibitor libraries led to the i  ...[more]

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