6-Bromoindirubin-3'-oxime derivatives are highly active colistin adjuvants against <i>Klebsiella pneumoniae</i>.
Li H, Mattingly AE, Smith RD, Melander RJ, Ernst RK, Melander C.
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 <i>Klebsiella pneumoniae</i>. 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.