The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol

Alex Boye; Justice Kwaku Addo; Desmond Omane Acheampong; Ama Kyeraa Thomford; Emmanuel Asante; Regina Elorm Amoaning; Dominic Nkwantabisa Kuma

doi:10.1016/j.heliyon.2020.e03492

The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol

Heliyon. 2020 Mar 17;6(3):e03492. doi: 10.1016/j.heliyon.2020.e03492. eCollection 2020 Mar.

Authors

Alex Boye¹, Justice Kwaku Addo², Desmond Omane Acheampong³, Ama Kyeraa Thomford³, Emmanuel Asante¹, Regina Elorm Amoaning¹, Dominic Nkwantabisa Kuma³

Affiliations

¹ Department of Medical Laboratory Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.
² Department of Chemistry, School of Physical Sciences, University of Cape Coast, Cape Coast, Ghana.
³ Department of Biomedical Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.

Abstract

Background: Thymol, a natural monoterpene phenol is not only relevant clinically as an anti-microbial, anti-oxidant and anti-inflammatory agent but also holds the prospect as a natural template for pharmaceutical semi-synthesis of therapeutic agents. It is a major component of essential oils from many plants. Evidence abound linking overall bioactivity of thymol to its monoterpene nucleus, specifically, the hydroxyl (-OH) substituent on carbon number one (C1) on the monoterpene nucleus. Other studies have posited that the overall bioactivity of thymol is not substantially altered by chemical modification of - OH on the C1 of the monoterpene nucleus. In view of this, it is still unclear as to whether removal or modification of the -OH on C1 of the monoterpene nucleus relates generally or context-dependently to bioactivity of thymol.

Objective: The present study investigated anti-bacterial effects of ester-and-ether substituted derivatives of thymol on S. aureus, P. aeruginosa and E. coli.

Materials and methods: twelve ester-and-ether substituted derivatives of thymol (6TM1s and 6TM2s) were synthesized and characterized by using HPLC, Mass spectrometry, and IR techniques. Anti-bacterial activity of the 12 thymol derivatives was evaluated using broth macrodilution and turbidimetric methods against pure clinical isolates (S. aureus, P. aeruginosa and E. coli). Standard anti-biotics used were Thymol Streptomycin and flucloxacillin, while DMSO was used as vehicle for thymol derivatives. MIC and MBC were determined.

Results: Thymol produced broad-spectrum growth inhibition on all isolates. At equimolar concentrations, thymol and reference drugs produced concentration-dependent growth inhibition against the isolates (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli) compared to DMSO. Although the growth inhibitory effects of the ester-and-ether derivatives of thymol was significant (P ≤ 0.05) compared to DMSO, it was however insignificant (P ≥ 0.05) compared to thymol and reference antibiotics. Comparatively, at equimolar concentrations, ester-substituted derivatives of thymol, particularly the branched chain derivative (TM1C) produced more effective growth inhibition on the isolates than the ether-substituted derivatives of thymol. Thymol was twice as potent (MIC and MBC, 500 μg/ml) than both ester-and-ether substituted derivatives of thymol (MIC and MBC, > 1000 μg/ml) on all the three clinical isolates. Increase in side chain bulkiness of -OH moiety on the monoterpene nucleus of thymol decreased growth inhibition on isolates.

Conclusion: Thymol has demonstrated broad-spectrum anti-bacterial effects attributable to the hydroxyl moiety on C1 of the monoterpene nucleus. Structural modification of the hydroxyl moiety on C1 of the monoterpene nucleus of thymol with either ether-or-ester substitutions yielded no significant anti-bacterial effects.

Keywords: Biological sciences; E. coli; Essential oils; Ester-substitution; Ether-substitution; Ethnopharmacology; Food toxicology; Health sciences; Monoterpenes; P. aeruginosa; Pharmacology; S. aureus; Structure activity relation; Thymol; Toxicology.