Design, synthesis and evaluation of a series of 5-methoxy-2,3-naphthalimide derivatives as AcrB inhibitors for the reversal of bacterial resistance

Chaobin Jin, Rawaf Alenazy, Yinhu Wang, Rumana Mowla, Yinhui Qin, Jin Quan Eugene Tan, Natansh Deepak Modi, Xinjie Gu, Steven W. Polyak, Henrietta Venter, Shutao Ma

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

A series of novel 5-methoxy-2,3-naphthalimide derivatives were designed, synthesized and evaluated for their biological activities. In particular, the ability of the compounds to synergize with antimicrobials, to inhibit Nile Red efflux, and to target AcrB was assayed. The results showed that the most of the tested compounds more sensitized the Escherichia coli BW25113 to the antibiotics than the parent compounds 7c and 15, which were able to inhibit Nile Red efflux. Significantly, compound A5 possessed the most potent antibacterial synergizing activity in combination with levofloxacin by 4 times and 16 times at the concentration of 8 and 16 µg/mL, respectively, whilst A5 could effectively abolish Nile Red efflux at 100 μM. Additionally, target effect of A5 was confirmed in the outer- or inner membrane permeabilization assays. Therefore, A5 is an excellent lead compound for further structural optimization.

Original languageEnglish
Pages (from-to)882-889
Number of pages8
JournalBioorganic & Medicinal Chemistry Letters
Volume29
Issue number7
DOIs
Publication statusPublished - 1 Apr 2019
Externally publishedYes

Keywords

  • 5-Methoxy-2,3-naphthalimide
  • AcrB
  • Antimicrobial resistance
  • Efflux pump inhibitor
  • Inhibition of efflux
  • Synergism

Fingerprint

Dive into the research topics of 'Design, synthesis and evaluation of a series of 5-methoxy-2,3-naphthalimide derivatives as AcrB inhibitors for the reversal of bacterial resistance'. Together they form a unique fingerprint.

Cite this