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
  • 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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