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Antibacterial, antifungal activities and toxicity of new synthetic fatty acid salicylate esters

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Abstract

Microbial threats and their resistance to the available drugs are public health concerns that scientists worldwide are trying to solve. Before the discovery of conventional drugs, natural products like fatty acids and salicylic acid derivatives had shown their effectiveness in fighting against pathogens and nowadays, they are considered as the next generation of antimicrobials. This study aiming to prepare new antibacterial and antifungal drugs, 24 new salicylate-fatty acids were designed and synthesized from fatty acids and salicylate derivatives and tested in vitro on several bacteria and fungi strains. It was found that salicylates covalently linked to palmitic acid had the best results with good (MIC = 31.25 μg/ml) and moderate (MIC = 62.5 and 125 μg/ml) antibacterial and antifungal activity against streptococcus pneumoniae, Staphylococcus aureus, Salomonella typhi, klebsiella pneumoniae, Escherichia coli, Trichophyton mentagrophytes, Microsporum audouinii, Epidermophyton floccosum and Microsporum gypseum. It was observed that saturated medium-chain (lauric, myristic) and unsaturated long-chain (oleic, linoleic, eleostearic) fatty acid units quenched the antimicrobial activity. Also, esterifying the phenolic OH and increasing the number of benzene ring reduced, on one hand the antibacterial activity of the compounds bearing the palmitic acid and, on the other, increased their antifungal activity. Acute toxicity experiments revealed that mono salicyl-palmitate is a relatively non-toxic substance since neither mortality nor changes in general behaviors of animals were recorded for 14 days after its oral administrations to mice with the median lethal dose (LD50) greater than 5000 mg/kg. Therefore, palmitic acid-salicylate esters are potential active ingredients for antimicrobial drugs.

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Acknowledgements

This work was carried out with the aid of a grant from UNESCO-TWAS and the Swedish International Development Cooperation Agency (Sida) (Grant number: 21-327 RG/CHE/AF/AC_G-FR32403). The views expressed herein do not necessarily represent those of UNESCO-TWAS, Sida or its Board of Governors.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Sciences, University of Douala, P.O. Box 2701, Douala, Cameroon

    Monique B. Ewonkem, Pascaline M. Deussom, Eunice N. Tiakouang, Alfred F. A. Toze & Duplex J. Wansi

  2. Department of Biochemistry, Laboratory of Biochemistry, Faculty of Science, University of Douala, P.O. Box 24 157, Douala, Cameroon

    Michel A. Mbock

  3. Department of Microbiology, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaoundé, Cameroon

    Michel A. Mbock

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  1. Monique B. Ewonkem
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Correspondence to Monique B. Ewonkem.

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Ewonkem, M.B., Deussom, P.M., Mbock, M.A. et al. Antibacterial, antifungal activities and toxicity of new synthetic fatty acid salicylate esters. Med Chem Res 32, 736–748 (2023). https://doi.org/10.1007/s00044-023-03034-w

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