Li Haoting, Mattingly Anne E, Smith Richard D, Melander Roberta J, Ernst Robert K, Melander Christian
Department of Chemistry and Biochemistry, University of Notre Dame Notre Dame Indiana 46556 USA
Department of Microbial Pathogenesis, University of Maryland Baltimore Maryland USA.
RSC Med Chem. 2022 Dec 1;14(2):247-252. doi: 10.1039/d2md00370h. eCollection 2023 Feb 22.
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 . 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.
多重耐药（MDR）细菌感染已变得越来越普遍，这使得临床医生依赖于诸如黏菌素等最后手段的抗生素。然而，由于多粘菌素耐药性的增加，黏菌素的效用正日益受到损害。最近我们发现，真核激酶抑制剂海葵环肽D的衍生物可消除几种革兰氏阴性菌中的黏菌素耐药性。随后对三个商业激酶抑制剂文库的筛选导致鉴定出了几种增强黏菌素活性的支架，包括6-溴靛玉红-3'-肟，其可有效抑制……中的黏菌素耐药性。在此我们报告了一个6-溴靛玉红-3'-肟类似物文库的活性，并鉴定出四种与母体化合物相比显示出同等或增强的黏菌素增强活性的衍生物。
