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<p>The emergence of resistance to traditional antibiotics in bacteria poses a serious problem for the healthcare. Therefore, the development of approaches to overcome microbial drug resistance is a challenge worldwide. While the design and construction of drugs with new targets is a labor-intensive procedure requiring the preparation of large libraries of compounds, the modification of conventional molecules with known antimicrobial activities to overcome the developed resistance is a relatively fast alternative approach. Here, metronidazole and chloramphenicol as model drugs were modified by incorporating a sesquiterpene fragment into their structures. It is known that 4,5-epoxycaryophyllan-8-ylmethanethiol has a wide spectrum of biological activity and, importantly, low cytotoxicity. This fact allowed the use of this sesquiterpenoid for drug modification. In the work, hybrid conjugates were obtained with a yield of 51–75%. Chloramphenicol in an alkaline medium was transformed into substituted dihydrooxazole. The synthesized thioterpene conjugates demonstrated MICs ​​against <i>S. aureus</i> and <i>P. aeruginosa</i> that exceeded those of conventional antibiotics. The low cytotoxicity of synthesized compounds allows considering them as promising start-compounds for further development of antimicrobial drugs.</p>

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S-containing conjugates of caryophyllene oxide with metronidazole and chloramphenicol: synthesis and antibacterial activity

  • 期刊论文

  • 发表日期：

    2025年8月22日

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  • Yulia V. Gyrdymova,
  • Airat R. Kayumov,
  • Svetlana V. Rubtsova

摘要

The emergence of resistance to traditional antibiotics in bacteria poses a serious problem for the healthcare. Therefore, the development of approaches to overcome microbial drug resistance is a challenge worldwide. While the design and construction of drugs with new targets is a labor-intensive procedure requiring the preparation of large libraries of compounds, the modification of conventional molecules with known antimicrobial activities to overcome the developed resistance is a relatively fast alternative approach. Here, metronidazole and chloramphenicol as model drugs were modified by incorporating a sesquiterpene fragment into their structures. It is known that 4,5-epoxycaryophyllan-8-ylmethanethiol has a wide spectrum of biological activity and, importantly, low cytotoxicity. This fact allowed the use of this sesquiterpenoid for drug modification. In the work, hybrid conjugates were obtained with a yield of 51–75%. Chloramphenicol in an alkaline medium was transformed into substituted dihydrooxazole. The synthesized thioterpene conjugates demonstrated MICs ​​against S. aureus and P. aeruginosa that exceeded those of conventional antibiotics. The low cytotoxicity of synthesized compounds allows considering them as promising start-compounds for further development of antimicrobial drugs.