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

• Published in: Journal of agricultural and food chemistry Vol. 56; no. 11; pp. 3989 - 3996
• Main Authors: MASTELIC, Josip, JERKOVIC, Igor, MÜLLER, Norbert, BLAZEVIC, Ivica, POLJAK-BLAZI, Marija, BOROVIC, Suzana, IVANCIC-BAZE, Ivana, SMRECKI, Vilko, ZARKOVIC, Neven, BRCIC-KOSTIC, Krunoslav, VIKIC-TOPIC, Drazen
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.06.2008; Amer Chemical Soc
• Subjects: Agriculture; Agriculture, Multidisciplinary; Anti-Infective Agents - pharmacology; Antifungal Agents - pharmacology; antimicrobial activity; antioxidant activity; Antioxidants - pharmacology; antiproliferative activity; antiyeast activity; Aroma and flavouring agent industries; Bioactive Constituents; bioactive properties; Biological and medical sciences; Carvacrol; Cell Division - drug effects; chemical concentration; chemical structure; Chemistry; Chemistry, Applied; cultured cells; cytotoxicity; diarylmethane derivative; dose response; Escherichia coli; Escherichia coli K12 - drug effects; eugenol; Eugenol - pharmacology; Food industries; Food microbiology; Food Science & Technology; Fundamental and applied biological sciences. Psychology; HeLa Cells; human cell lines; Humans; hydroxymethyl derivatives; leukemia; Life Sciences & Biomedicine; metabolites; Monoterpenes - pharmacology; phenolic compounds; Physical Sciences; Saccharomyces cerevisiae; Science & Technology; thymol; Thymol - pharmacology; viability; thymol; antiyeast activity; hydroxymethyl derivatives; Carvacrol; eugenol; antimicrobial activity; diarylmethane derivative; antioxidant activity; antiproliferative activity; ACID; LIPID OXIDATION; ESSENTIAL OILS; HYDROGEN-ATOM; FOODS; PHENOLS; anti proliferative activity; PLANT-EXTRACTS; carvacrol; Antineoplastic agent; Antioxidant; Eugenol; Biological activity; Antimicrobial agent; Essential oil
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf073272v

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 µg/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.