Synthesis of 1,2,3-triazole-thymol derivatives as potential antimicrobial agents

Justice Kwaku Addo; Ernest Owusu-Ansah; Nicholas T K D Dayie; Xavier Cheseto; Baldwyn Torto

doi:10.1016/j.heliyon.2022.e10836

Synthesis of 1,2,3-triazole-thymol derivatives as potential antimicrobial agents

Heliyon. 2022 Oct 1;8(10):e10836. doi: 10.1016/j.heliyon.2022.e10836. eCollection 2022 Oct.

Authors

Justice Kwaku Addo^{1

2}, Ernest Owusu-Ansah¹, Nicholas T K D Dayie³, Xavier Cheseto², Baldwyn Torto²

Affiliations

¹ Department of Chemistry, School of Physical Sciences, University of Cape Coast, Ghana.
² International Centre of Insect Physiology and Ecology (icipe), P.O. Box 30772-00100, Nairobi, Kenya.
³ Department of Medical Microbiology, University of Ghana Medical School, P.O. Box 4236, Korle-Bu, Accra, Ghana.

Abstract

Background: Thymol as a natural biological template can be modified chemically since the hydroxyl group makes it a candidate for structural modification. Thus, this study incorporated the triazole moiety on thymol and the chlorination of thymol moiety to help improve its biological potency.

Materials and methods: A series of ten 1,2,3-triazole-thymol derivatives 1-10 were synthesized from thymol, by a click reaction between O-propargyl terminal alkyne of thymol and its chlorothymol with benzyl azide and substituted benzyl azides. Their structures were confirmed by spectroscopic methods (¹H-NMR, ¹³C-NMR, IR, GC-MS-EI/CI and LC-ESI-QTOF-MS). The Well diffusion method using Müeller-Hinton agar plates was used to demonstrate the antimicrobial activities of the synthesized triazole-thymol derivatives on selected bacterial strains; Escherichia coli ATCC 25922, Staphylococcus aureus ATCC25923, Methicillin resistant S. aureus (MRSA), Pseudomonas aeruginosa ATCC 29853, E. coli ESBL, K l ebsiella pneumoniae NCTC 13438 and Meropenem Resistant E. coli.

Results: All the synthesized triazole-thymol derivatives showed significant but variable antibacterial activity against the seven medically important bacterial strains tested. The compound 4-((4-chloro-2-isopropyl-5-methylphenoxy)methyl)-1-(2-nitrobenzyl)-1H-1,2,3triazole (9) demonstrated a higher antibacterial activity with a mean zone of inhibition (38.7 mm) compared with ampicillin as the positive control which gave a zone size of 30.0 mm. In addition, the compound showed a three-fold potency than the parent compound, thymol (11.0 mm) against MRSA at a concentration of 100 μg/ml.

Conclusion: These results provide additional evidence of the exploitation of natural products like thymol as leads for drug development against medically important bacterial pathogens.

Keywords: Ampicillin; Antibacterial activity; Essential oil; Monoterpenoid; Thymol; Triazole.