ISSN print edition: 0366-6352
ISSN electronic edition: 1336-9075
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S-containing conjugates of caryophyllene oxide with metronidazole and chloramphenicol: synthesis and antibacterial activity

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

Institute of Chemistry, FRC Komi Scientific Center, Ural Branch of the RAS, Syktyvkar, Russian Federation

Received: 17 December 2024 Accepted: 11 August 2025

Abstract:

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.

Keywords: Metronidazole; Chloramphenicol; Caryophyllene oxide; Sesquiterpene thiol; Antibacterial activity

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04309-9

Chemical Papers 79 (11) 8105–8116 (2025)

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