title: 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.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry and Technology, University of Split, Split, Croatia. josip.mastelic@ktf-split.hr
authors.forename: Josip
authors.initials: J
authors.lastname: Mastelić
authors.forename: Igor
authors.initials: I
authors.lastname: Jerković
authors.forename: Ivica
authors.initials: I
authors.lastname: Blazević
authors.forename: Marija
authors.initials: M
authors.lastname: Poljak-Blazi
authors.forename: Suzana
authors.initials: S
authors.lastname: Borović
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivancić-Baće
authors.forename: Vilko
authors.initials: V
authors.lastname: Smrecki
authors.forename: Neven
authors.initials: N
authors.lastname: Zarković
authors.forename: Krunoslav
authors.initials: K
authors.lastname: Brcić-Kostic
authors.forename: Drazen
authors.initials: D
authors.lastname: Vikić-Topić
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D000081007:Cymenes; D048168:Escherichia coli K12 / Q000187:drug effects; D005054:Eugenol / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D039821:Monoterpenes / Q000494:pharmacology*; D013943:Thymol / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000975:Antioxidants; D000081007:Cymenes; D039821:Monoterpenes; D013943:Thymol; D005054:Eugenol; C073316:carvacrol