Introduction. The essential oil of Thymus vulgaris has antimicrobial, carminative and expectorant activities, which are attributed the presence of thymol and carvacrol, with thymol being the most effective. Thymol is a phenolic compound with low molecular weight and naturally produced by plants and microorganisms during normal development or due to stress conditions such as injury, infection or exposure to UV radiation. Recent interest in this compound is based on the potential benefits such as for antifungal, pesticide, antibacterial and other activities.
Aim. Thus considering the several biological properties described for thymol and its derivatives and the importance and necessity of the discovery of new drugs effective for antitumor therapy, this work aims to carry out the preparation of novel compounds derived from thymol through Williamson synthesis, as well as evaluation of antitumor activity.
Methods. Thymol (0,05g, 0.33mmol), potassium carbonate (0,045g, 0,33mol), in 4 ml of DMF (dimethylformamide) were kept under stirring on an ice bath for 20 minutes. Then commercial bromide (0,05mmol) was added. Subsequently, the reaction mixture was stirred at room temperature for 4 h. Finally, a chromatographic column was performed using hexane/ethyl acetate or diethyl ether (7:3 or 10:1) as eluent. Results. The use of natural product thymol as scaffold allowed the generation of derivatives 1-isopropyl-4-methyl-2-((4-nitrobenzyl)oxy)benzene (2a), 1-isopropyl-4-methyl-2-(prop-2-yn-1-yloxy)benzene (2b) and 1-isopropyl-4-methyl-2-((2-((phenylsulfonyl)methyl)benzyl)oxy)benzene (2c). All compounds were elucidated by HPLC and 1H NMR spectroscopic analysis.
Conclusion. Further reactions in order to prepare novel thymol derivatives are ongoing as well as antitumor activity evaluation.