Pyrazoles: A Master Key to Tackle Multidrug-Resistant Acinetobacter baumannii and Its Structure Activity Relationship Studies

Chem Biol Drug Des. 2025 Mar;105(3):e70092. doi: 10.1111/cbdd.70092.

Abstract

Infections caused by Gram-negative bacteria within the ESKAPE group pose significant treatment challenges. These bacteria feature effective efflux pumps and possess lipopolysaccharides in their outer membranes, as well as a thin peptidoglycan layer measuring 5-10 nm in thickness. Acinetobacter baumannii (A. baumannii), a Gram-negative bacterium, is a significant contributor to serious infections acquired in hospitals and communities, representing a substantial risk to human health. This bacterium has developed resistance to nearly all existing antibiotics, and in the past 50 years, no new antibacterial class has been introduced for treating A. baumannii infections, highlighting an urgent necessity for the development of new antibacterials. The unique structural framework and adaptable features of the pyrazole ring attract researchers to develop new antibiotics. The present study outlines the advancements made over the last decade in pyrazole-containing derivatives that exhibit a wide range of antibacterial activity against various bacterial strains. Specifically, we discuss the effectiveness of diverse pyrazole derivatives against multidrug-resistant A. baumannii strains and explore various aspects of the structure-activity relationship (SAR). This compilation of data could serve as an excellent platform for designing and developing new pyrazole-based small molecules to target the growth of A. baumannii.

Keywords: Acinetobacter baumannii; Gram‐negative; Pyrazole; SAR; drug discovery.

Publication types

  • Review

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii* / drug effects
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Drug Resistance, Multiple, Bacterial* / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacology
  • Structure-Activity Relationship

Substances

  • Pyrazoles
  • Anti-Bacterial Agents