Synthesis of Hydrazone Derivatives of 4-[4-Formyl-3-(2-oxochromen-3-yl)pyrazol-1-yl]benzoic acid as Potent Growth Inhibitors of Antibiotic-resistant Staphylococcus aureus and Acinetobacter baumannii

Molecules. 2019 May 29;24(11):2051. doi: 10.3390/molecules24112051.

Abstract

Microbial resistance to drugs is an unresolved global concern, which is present in every country. Developing new antibiotics is one of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat bacterial resistance to drugs. Based on our lead molecules, we report the synthesis and antimicrobial studies of 27 new pyrazole derivatives. These new coumarin-pyrazole-hydrazone hybrids are readily synthesized from commercially available starting materials and reagents using benign reaction conditions. All the synthesized molecules were tested against 14 Gram-positive and Gram-negative bacterial strains. Several of these molecules have been found to be potent growth inhibitors of several strains of these tested bacteria with minimum inhibitory concentrations as low as 1.56 μg/mL. Furthermore, active molecules are non-toxic in in vitro and in vivo toxicity studies.

Keywords: Acinetobacter baumannii; Coumarin; ESKAPE pathogen; MRSA; Staphylococcus aureus; antimicrobials; drug-resistant; hydrazone; pyrazole.

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / metabolism
  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Drug Resistance, Bacterial / drug effects*
  • Humans
  • Hydrazones / chemical synthesis*
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism

Substances

  • Anti-Bacterial Agents
  • Hydrazones