Synthesis, Antimicrobial Activity and in silico Studies on Thymol Esters

Abstract

Derivatisation of parent structure in terpenoids often results in enhancement of biological activity of newly obtained compounds. Thymol, a naturally occurring phenol biosynthesized through the terpene pathway, is a well known biocide with strong antimicrobial attributes and diverse therapeutic activities. We have aimed our study on a single modification of phenolic functionality in thymol in order to obtain a small focused library of twenty thymyl esters, ten of which were new compounds. All compounds were involved in in vitro antimicrobial testing. Another important aspect of current study was implementation of in silico calculation of physico-chemical, pharmacokinetic and toxicological properties, which could be helpful by giving an additional guidance in further research.

Synthesis, Antimicrobial Activity and in silico Studies on Eugenol Eters

“…The results have indicated microorganisms' selective susceptibility, with B. subtilis (3d, 3l, 3n-r), S. aureus (3e and 3f), C. albicans (3d, 3f, 3n, 3r-s) and A. niger (3f, 3s) as the most susceptible ones, with minimal inhibitory or cidal concentrations (MIC/MBC/MFC) never exceeding the range of activity of eugenol as the parent compound. Based on current results and on our previously published ones, 43 having in best case comparable but never greater MIC values than for parent phenolic compound we could not confirm results obtained by previous groups. [29][30][31] Our results have shown the importance of free phenolic hydroxyl group in terms of activity against microbials, however more detailed research should be conducted involving also a more complex viewpoint, as for instance, the disclosure of mechanism of action of eugenyl esters on bacteria and fungi.…”

“…For the preparation of acyl chlorides 2b-p, 2r and of eugenyl esters (Table 1, entries 3a-s) methods from the literature [39][40][41][42] were utilized and general procedures for the synthesis as reported in our previously published paper was followed. 43 Scheme 1 represents the synthesis of eugenyl esters.…”

Synthesis, Larvicidal and Acetylcholinesterase Inhibitory Activities of Carvacrol/Thymol and Derivatives

“…25 The hydrophobic nature of carvacrol and thymol interact with the lipid bilayer of cytoplasmic membranes cause loss of integrity and leakage of cellular material such as ions, ATP and nucleic acid. 26 Generally, the derivatization of hydroxylated monoterpenes results in enhancement of larvicidal activity against Aedes aegypti of newly obtained compounds, because the presence of hydroxyl groups on their parent structures results in decreased potency, preventing substance penetration in the larva cuticle, [27][28][29][30][31] although this may also result in a decreased activity. 32 Thus, the synthesis of derivatives of carvacrol/thymol by simple synthetic procedures, such as acylation, consists of a method of obtaining these compounds.…”

Thymol as an Interesting Building Block for Promising Fungicides against Fusarium solani

“…Terpenoids reveal a broad and potent class of natural products with a remarkable role in the enzyme systems of plants and highlight an important biological activity against several pests . Furthermore, semisynthesis using these natural products as scaffolds has been reported to improve biological activities. − Thymol is a naturally occurring phenolic monoterpenoid, well-known biocide, and major compound of the oils of thyme ( Thymus vulgaris L.) and oregano ( Origanum vulgare L.). Derivatives of this natural product are easily observed in Asteraceae plants, particularly in Senecioneae, Eupatorieae, Inuleae and Helenieae tribes. − Several works have highlighted its biological activities like antimutagenic, , anthelmintic, − antiseptic; gastro protective activity against several strains of Helicobacter pylori . , In addition, thymol has interesting antitumor properties and is an effective fungicide, particularly against fluconazole-resistant strains, and it has inhibitory activity against plants’ pathogenic fungi. , The mode of thymol action against fungi is due to its ability to modify the hyphal structure and hyphal agglomeration, promoting reduction in hyphal diameters and lysis of hyphal wall.…”