2. Academic Validation
  3. Discovery of unique thiazolidinone-conjugated coumarins as novel broad spectrum antibacterial agents

Discovery of unique thiazolidinone-conjugated coumarins as novel broad spectrum antibacterial agents

  • Eur J Med Chem. 2022 Mar 15;232:114192. doi: 10.1016/j.ejmech.2022.114192.
Xun-Cai Yang 1,  Peng-Li Zhang 1,  Kannekanti Vijaya Kumar 1,  Shuo Li 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 Chemical Engineering, Chongqing University of Technology, Chongqing, 400054, PR 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: 35168149 DOI: 10.1016/j.ejmech.2022.114192
Abstract

Unique coumarin conjugates with thiazolidinone as novel structural Antibacterial modulators were exploited to combat the lethal multidrug-resistant Bacterial infections. Bioactivity evaluation identified that indole-incorporated coumarin thiazolidinone conjugate 14a with low cytotoxicity to mammalian cells showed a broad Antibacterial spectrum and exerted potent inhibition efficiencies to the tested germs at low concentrations (0.25-2 μg/mL). Moreover, the favorable performance of 14a in eradicating Bacterial biofilm was beneficial to avert developing drug resistance. Mechanistic explorations revealed that molecule 14a was able to destroy cell membrane, leading to the leakage of intracellular Materials and metabolism inhibition. The accumulation of excess Reactive Oxygen Species (ROS) mediated by compound 14a could impede glutathione (GSH) activity and induce lipid peroxidation to suppress bacteria growth. Furthermore, compound 14a could not only intercalate into DNA base pair but also take part in non-covalent interaction with DNA gyrase B to hinder their biological function. Quantum chemical study indicated that molecule 14a had low HOMO-LUMO energy gap, which resulted in more stabilizing interactions and was conducive to displaying better Antibacterial activity. ADMET analysis manifested that 14a possessed promising pharmacokinetic properties.

Keywords

Antibacterial; Coumarin; Resistance; Thiazolidinone.

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