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The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol
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 ma...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078539/ https://www.ncbi.nlm.nih.gov/pubmed/32195386 http://dx.doi.org/10.1016/j.heliyon.2020.e03492 |
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author | Boye, Alex Addo, Justice Kwaku Acheampong, Desmond Omane Thomford, Ama Kyeraa Asante, Emmanuel Amoaning, Regina Elorm Kuma, Dominic Nkwantabisa |
author_facet | Boye, Alex Addo, Justice Kwaku Acheampong, Desmond Omane Thomford, Ama Kyeraa Asante, Emmanuel Amoaning, Regina Elorm Kuma, Dominic Nkwantabisa |
author_sort | Boye, Alex |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7078539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-70785392020-03-19 The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol Boye, Alex Addo, Justice Kwaku Acheampong, Desmond Omane Thomford, Ama Kyeraa Asante, Emmanuel Amoaning, Regina Elorm Kuma, Dominic Nkwantabisa Heliyon Article 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. Elsevier 2020-03-17 /pmc/articles/PMC7078539/ /pubmed/32195386 http://dx.doi.org/10.1016/j.heliyon.2020.e03492 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Boye, Alex Addo, Justice Kwaku Acheampong, Desmond Omane Thomford, Ama Kyeraa Asante, Emmanuel Amoaning, Regina Elorm Kuma, Dominic Nkwantabisa The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol |
title | The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol |
title_full | The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol |
title_fullStr | The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol |
title_full_unstemmed | The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol |
title_short | The hydroxyl moiety on carbon one (C1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol |
title_sort | hydroxyl moiety on carbon one (c1) in the monoterpene nucleus of thymol is indispensable for anti-bacterial effect of thymol |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078539/ https://www.ncbi.nlm.nih.gov/pubmed/32195386 http://dx.doi.org/10.1016/j.heliyon.2020.e03492 |
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