2. Academic Validation
  3. Pyrrole-thiazolidinone hybrids as a new structural class of broad-spectrum anti-infectives

Pyrrole-thiazolidinone hybrids as a new structural class of broad-spectrum anti-infectives

  • Eur J Med Chem. 2023 Nov 15:260:115757. doi: 10.1016/j.ejmech.2023.115757.
Shujauddin Ahmed 1,  Alka Mital 1,  Abdul Akhir 2,  Deepanshi Saxena 2,  Mohammad Naiyaz Ahmad 2,  Arunava Dasgupta 3,  Sidharth Chopra 4,  Rahul Jain 5
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab, 160 062, India.
  • 2 Division of Molecular Microbiology and Immunology, Central Drug Research Institute (CSIR-CDRI), Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh, 226 031, India.
  • 3 Division of Molecular Microbiology and Immunology, Central Drug Research Institute (CSIR-CDRI), Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh, 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India.
  • 4 Division of Molecular Microbiology and Immunology, Central Drug Research Institute (CSIR-CDRI), Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh, 226 031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India. Electronic address: [email protected].
  • 5 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab, 160 062, India. Electronic address: [email protected].
PMID: 37659197 DOI: 10.1016/j.ejmech.2023.115757
Abstract

A series of pyrrole-thiazolidinone hybrids was designed, synthesized and evaluated for activities against ESKAP bacteria panel and mycobacterial pathogens. From the series, compound 9d showed prominent activity against S. aureus (MIC = 0.5 μg/mL) and compound 9k showed the most promising activity against M. tuberculosis H37Rv (MIC = 0.5 μg/mL). Potent derivatives were found to be non-toxic when tested against Vero cells. Compound 9d upon evaluation in vitro against several MRSA and VRSA strains produced activity comparable or better than standard drugs. In the anti-biofilm assay, 9d reduced S. aureus biofilm by >11% at 10x MIC. The dual inhibitory effect exhibited by pyrrole-thiazolidinone hybrids confirms their potential as new class of promising anti-infective agents.

Keywords

Anti-TB; Antimicrobial; ESKAP bacteria; Pyrrole; Thiazolidinone.

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