Carvacrol Derivatives as Antifungal Agents: Synthesis, Antimicrobial Activity and in Silico Studies on Carvacryl Esters.

Chemical modifications of natural monoterpenoids to various derivatives have been reported to result in enhancement of biological activities when compared to parent compounds. In this context a well-known biocide and food additive, carvacrol, served as a basic scaffold onto which a phenolic functionality transformation by introducing acyl groups was performed. By using this simple methodology, we obtained a small series of 25 esters. For each of the obtained compounds we have performed structural characterization, in vitro antimicrobial testing and in silico calculation of physico-chemical, pharmacokinetic and toxicological properties. Despite numerous data on the synthesis and bioactivity of carvacryl ester lower homologues, there are scarce data on esters with acid components higher than C9, so that among 25 compounds, 10 were reported for the first time (spectral characterization for 12 are herein the first reported). Our research is also the first comprehensive study of carvacryl esters antifungal and of medium/long chain fatty acid esters antibacterial activities. Interesting result is that all the synthesized esters, regardless the nature of the R residue, have shown activity on fungal strain Aspergilus niger and on yeast Candida albicans comparable to carvacrol. Besides presented experimental data, implementation of in silico calculation of physico-chemical, pharmacokinetic and toxicological properties on the prepared compounds, may be valuable information in further research.