2. Academic Validation
  3. Novel coumarin aminophosphonates as potential multitargeting antibacterial agents against Staphylococcus aureus

Novel coumarin aminophosphonates as potential multitargeting antibacterial agents against Staphylococcus aureus

  • Eur J Med Chem. 2023 Jan 5;245(Pt 1):114891. doi: 10.1016/j.ejmech.2022.114891.
Xun-Cai Yang 1,  Chun-Mei Zeng 1,  Srinivasa Rao Avula 1,  Xin-Mei Peng 2,  Rong-Xia Geng 3,  Cheng-He Zhou 4
Affiliations

Affiliations

  • 1 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China.
  • 2 School of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun, 558000, China. Electronic address: [email protected].
  • 3 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China. Electronic address: [email protected].
  • 4 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China. Electronic address: [email protected].
PMID: 36343412 DOI: 10.1016/j.ejmech.2022.114891
Abstract

Unique coumarin aminophosphonates as new Antibacterial agents were designed and synthesized to combat severely Bacterial resistance. Bioactivity assessment identified that 3-hydroxylphenyl aminophosphonate 6f with low hemolytic activity not only exhibited excellent inhibition potency against Staphylococcus aureus at low concentration (0.5 μg/mL) in vitro but also showed considerable Antibacterial potency in vivo. Meanwhile, the active compound 6f was capable of eradicating the S. aureus biofilm, thus alleviating the development of S. aureus resistance. Furthermore, the drug combination of compound 6f with norfloxacin could enhance the Antibacterial efficacy. Mechanistic explorations manifested that molecule 6f was able to destroy the integrity of cell membrane, which resulted in the leakage of protein and metabolism inhibition. The cellular redox homeostasis was interfered through inducing the generation of Reactive Oxygen Species (ROS) and reactive nitrogen species (RNS), leading to the reduction of glutathione (GSH) activity and lipid peroxidation. Furthermore, compound 6f could intercalate into DNA base pair to hinder normal biological function. The above results provided powerful information for the further development of coumarin aminophosphonates as Antibacterial agents.

Keywords

Aminophosphonate; Coumarin; Resistance; Staphylococcus aureus.

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