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PreprintCC BYChemRxiv

THIOETHERS AS POTENTIAL ANTIBACTERIAL AGENTS AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)

  • Aditya G Lavekar1,2
  • Radha Ahuja3,4
  • Deepti Gairola5,6
6 affiliations
  1. 1Medicinal and Process Chemistry Division
  2. 2CSIR-Central Drug Research Institute
  3. 3Department of Chemistry
  4. 4Punjab Agricultural University
  5. 5Chemistry Division
  6. 6Indian Institute of Technology Roorkee
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Abstract

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) have created an urgent need for new antibacterial agents capable of overcoming established resistance mechanisms. Among the diverse sulfur-containing scaffolds, thioethers have attracted increasing attention because of their structural versatility and ability to modulate antibacterial activity through incorporation into different pharmacophores. This review provides a comprehensive overview of synthetic, semisynthetic, and natural or natural-product-derived thioether compounds evaluated against MRSA, with emphasis on their structural features, structure-activity relationships (SAR), antibacterial potency, and mechanisms of action. The major classes discussed include aminoglycoside-derived thioether amphiphiles, membrane-active small-molecule thioethers, quinazolinone and quinoline thioether scaffolds, pleuromutilin thioether derivatives, SecA-targeting thioethers, chalcone and oxazolidinone derivatives, FtsZ-targeting thioethers, anti-virulence and antibiofilm agents, antimicrobial peptidomimetics, and natural-product-derived thioether compounds. The studies demonstrate that sulfur-containing motifs can contribute to anti-MRSA activity through membrane disruption, inhibition of bacterial protein synthesis and targeting of essential non-ribosomal proteins. The available SAR evidence highlights the scaffold-dependent nature of thioether activity and supports their continued exploration as versatile structural motifs for the development of new therapeutic strategies against drug-resistant MRSA.

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Cite

BibTeXRIS
BibTeX
@misc{lavekar2026thioethers,
  title = {{THIOETHERS AS POTENTIAL ANTIBACTERIAL AGENTS AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)}},
  author = {Aditya G Lavekar and Radha Ahuja and Deepti Gairola},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15008364/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008364/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - THIOETHERS AS POTENTIAL ANTIBACTERIAL AGENTS AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)
AU  - Aditya G Lavekar
AU  - Radha Ahuja
AU  - Deepti Gairola
PY  - 2026
DA  - 2026/09/06
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15008364/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008364/v1
AB  - The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) have created an urgent need for new antibacterial agents capable of overcoming established resistance mechanisms. Among the diverse sulfur-containing scaffolds, thioethers have attracted increasing attention because of their structural versatility and ability to modulate antibacterial activity through incorporation into different pharmacophores. This review provides a comprehensive overview of synthetic, semisynthetic, and natural or natural-product-derived thioether compounds evaluated against MRSA, with emphasis on their structural features, structure-activity relationships (SAR), antibacterial potency, and mechanisms of action. The major classes discussed include aminoglycoside-derived thioether amphiphiles, membrane-active small-molecule thioethers, quinazolinone and quinoline thioether scaffolds, pleuromutilin thioether derivatives, SecA-targeting thioethers, chalcone and oxazolidinone derivatives, FtsZ-targeting thioethers, anti-virulence and antibiofilm agents, antimicrobial peptidomimetics, and natural-product-derived thioether compounds. The studies demonstrate that sulfur-containing motifs can contribute to anti-MRSA activity through membrane disruption, inhibition of bacterial protein synthesis and targeting of essential non-ribosomal proteins. The available SAR evidence highlights the scaffold-dependent nature of thioether activity and supports their continued exploration as versatile structural motifs for the development of new therapeutic strategies against drug-resistant MRSA.
ER  -