6-Bromoindirubin-3′-oxime derivatives are highly active colistin adjuvants against Klebsiella pneumoniae. Issue 2 (14th December 2022)

• Record Type: Journal Article
• Authors: Li, Haoting; Mattingly, Anne E.; Smith, Richard D.; Melander, Roberta J.; Ernst, Robert K.; Melander, Christian
• Is Part Of: RSC medicinal chemistry. Volume 14:Issue 2(2023)
• Page Start: 247
• Page End: 252
• Publication Date: 2022-12-14
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1039/d2md00370h
• Languages: English
• ISSNs: 2632-8682

Abstract

Abstract : Multidrug resistant (MDR) bacterial infections have become increasingly common, leading clinicians to rely on last-resort antibiotics such as colistin. 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.