Comparative Study on the Antioxidant and Biological Activities of Carvacrol, Thymol, and Eugenol Derivatives

Abstract

Four derivatives of thymol, carvacrol, and eugenol were synthesized: 4-(hydroxymethyl)-5-isopropyl-2-methylphenol, 4,4'-methylenebis(5-isopropyl-2-methyl)phenol, 4-allyl-6-(hydroxymethyl)-2-methoxyphenol, and 4-(hydroxymethyl)-2-isopropyl-5-methylphenol. The obtained derivatives showed remarkably better antioxidative properties according to 1,1-diphenyl-2-picrylhydrazyl assay (50% inhibitory concentrations = 4-156 microg/mL) and Rancimat assay (protection factors = 1.55-5.84) when compared with parent compounds and values similar to or better than those of butylated hydroxytoluene and vitamin C. At concentrations of 10 mM carvacrol derivatives had no toxic effect on viability of Escherichia coli K-12 (determined by minimum inhibitory concentrations). Other phenol derivatives showed reduced cytotoxic effect on E. coli K-12 at concentrations of 2-5 mM on the basis of 50% lethal dose measurements. In comparison with the parent compounds, phenol derivatives showed reduced cytotoxic effect for Saccharomyces cerevisiae cells (determined by yeast colony reduction). On the other hand, the majority of synthesized compounds had dose-dependent antiproliferative effects on human uterine carcinoma cells (HeLa), which makes them potentially interesting for the adjuvant experimental cancer treatments. The 4,4'-methylenebis(5-isopropyl-2-methyl)phenol derivative of carvacrol showed lower inhibiting capacity also for the HeLa cells, which makes this particular derivative attractive as an efficient antioxidant with negligible cytotoxic effects.

A carvacrol–thymol blend decreased intestinal oxidative stress and influenced selected microbes without changing the messenger RNA levels of tight junction proteins in jejunal mucosa of weaning piglets

“…A diet supplemented with 100 mg/kg carvacrol-thymol (1 : 1) blend reduced weaning-induced oxidative stress. Both carvacrol and thymol have free radical scavenging activity (Mastelic et al, 2008;Archana et al, 2009;Safaei-Ghomi et al, 2009). In the current study, increased activity of antioxidants in the jejunum was observed in the weaned-CB group compared with the weaned group.…”

“…Both carvacrol and thymol possess in vitro ROSscavenging activity (Mastelic et al, 2008). In addition, it has been demonstrated that either carvacrol or thymol alone, or in combination, has antibacterial properties to inhibit growth of E. faecalis and E. coli (Michiels et al, 2009;Guarda et al, 2011;Gutiérrez-Fernández et al, 2013).…”

Synthesis of 2-Methoxy-4,6-Di(prop-1-Enyl)phenol From Eugenol and Its Activity as an Antioxidant

“…1 H and 13 C-NMR spectra were obtained on JEOL JN ECA -500 (500 MHz). Mass spectra were recorded on Shimadzu GCS QP-2010S.…”

“…Oxidative stress, caused by an imbalance between antioxidant systems and the production of oxidants, seems to be associated with many diseases, especially cancers, cardiovascular diseases and inflammatory disorders [1]. The mechanisms by which these pathologies grow generally involve oxidative alteration of physiologically critical molecules, including proteins, lipids, carbohydrates, and nucleic acids, along with the modulation of gene expression and inflammatory response [2].…”

“…Some eugenol derivatives have been synthesized to increase their antioxidant properties. Nur'aini et al [7] prepared Mannich derivatives, Hidalgo et al [8] synthesized acetic ester derivatives, glycoside derivatives have been produced by Tominaga et al [9], while Mastelic [1] prepared the hydroxyl methyl derivatives of eugenol. However those results have not revealed significant improvement.…”