Synthesis and tyrosinase inhibitory activities of 4-oxobutanoate derivatives of carvacrol and thymol

Brotzman, Nicholas; Xu, Yiming; Graybill, Allison; Cocolas, Alexander H.; Ressler, Andrew; Seeram, Navindra P.; Ma, Hang; Henry, Geneive E.

doi:10.1016/j.bmcl.2018.11.013

Cited by 23 publications

(13 citation statements)

References 16 publications

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“…Rather low IC50 values have been determined also for resveratrol derivatives such as (E)-2,3-bis(4-hydroxyphenyl)acrylonitrile (IC50 = 5.06 μM) [169] and dihydrooxyresveratrol glucosides [170] (Figure 19). As to other natural phenol-inspired synthetic compounds [157][158][159][160][161], the best results have been reported for a carvacrol derivative containing a 3,5-dihydroxyphenyl moiety (IC 50 = 0.0167 µM) [159] ( Figure 19). Good inhibition properties have been exhibited also by some rhododendrol glycosides (IC 50 = 0.56-9.15 µM) [160] and eugenol derivatives (IC 50 ca.…”

Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 98%

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

2019

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One of the most common approaches for control of skin pigmentation involves the inhibition of tyrosinase, a copper-containing enzyme which catalyzes the key steps of melanogenesis. This review focuses on the tyrosinase inhibition properties of a series of natural and synthetic, bioinspired phenolic compounds that have appeared in the literature in the last five years. Both mushroom and human tyrosinase inhibitors have been considered. Among the first class, flavonoids, in particular chalcones, occupy a prominent role as natural inhibitors, followed by hydroxystilbenes (mainly resveratrol derivatives). A series of more complex phenolic compounds from a variety of sources, first of all belonging to the Moraceae family, have also been described as potent tyrosinase inhibitors. As to the synthetic compounds, hydroxycinnamic acids and chalcones again appear as the most exploited scaffolds. Several inhibition mechanisms have been reported for the described inhibitors, pointing to copper chelating and/or hydrophobic moieties as key structural requirements to achieve good inhibition properties. Emerging trends in the search for novel skin depigmenting agents, including the development of assays that could distinguish between inhibitors and potentially toxic substrates of the enzyme as well as of formulations aimed at improving the bioavailability and hence the effectiveness of well-known inhibitors, have also been addressed.

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Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 98%

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

2019

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“…Skin color is considered important in the contexts of fashion and beauty, but the overproduction of melanin due to, for example, excessive UV exposure results in hyperpigmentation, spots, freckles, and melasma [16] , [17] , [18] , [19] , [20] . Melanin is biosynthesized in the melanosomes of melanocytes by complicated enzymatically driven processes.…”

Section: Introductionmentioning

confidence: 99%

In silico and in vitro insights into tyrosinase inhibitors with a 2-thioxooxazoline-4-one template

Choi

Park

Ryu

et al. 2021

Computational and Structural Biotechnology Journal

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“…Evidence abound that generally attribute the overall biological activity of monoterpene phenols such as thymol to the hydroxyl (-OH) substituent on carbon number one (C1) on the monoterpene nucleus [22,23,24]. Others studies have also demonstrated that the overall bioactivity of monoterpene phenols is not altered by the presence or absence or changing the position of the hydroxyl moiety (-OH) on the monoterpene nucleus [24,25,26].…”

Section: Introductionmentioning

confidence: 99%

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

Boye¹,

Addo²,

Acheampong³

et al. 2020

Heliyon

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Background: Thymol, a natural monoterpene phenol is not only relevant clinically as an anti-microbial, antioxidant and anti-inflammatory agent but also holds the prospect as a natural template for pharmaceutical semisynthesis 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 antibiotics 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.

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Synthesis and tyrosinase inhibitory activities of 4-oxobutanoate derivatives of carvacrol and thymol

Cited by 23 publications

References 16 publications

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

In silico and in vitro insights into tyrosinase inhibitors with a 2-thioxooxazoline-4-one template

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

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