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.

Synthesis, Antimicrobial Activity and in silico Studies on Eugenol Eters.

The results presented herein represent our continued study based on the modification of phenolic functionality in molecules originated from natural sources by acylation. A small focused library of nineteen eugenyl esters, with four of which are new compounds, is reported. All compounds were subjected to in vitro antimicrobial testing. In silico studies were carried out calculating physico-chemical, pharmacokinetic and toxicological properties, providing more data as additional guidance for further research.

Determination of the serine palmitoyl transferase inhibitor myriocin by electrospray and Q-trap mass spectrometry.

Myriocin is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure myriocin in minute specimens of animal tissue. The chemical analog 14-OH-myriocin was used as the internal standard. The two molecules were extracted from the tissue homogenate by solid-phase extraction, separated by gradient reversed-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole. Detection was accomplished by multiple reaction monitoring, employing the most representative transitions, 400@104 and 402@104 for myriocin and 14-OH-myriocin, respectively. The typical limit of detection and lower limit of quantitation of the optimized method were 0.9 pmol/mL (~0.016 pmol injected) and 2.3 pmol/mL, respectively, and the method was linear up to 250 pmol/mL range (r2 = 0.9996). The intra- and between-day repeatability afforded a coefficient of variation ≤7.0%. Applications included quantification of myriocin in mouse lungs after 24 h from administration of ~4 nmol by intra-tracheal delivery. Measured levels ranged from 4.11 (median; 2.3-7.4 IQR, n = 4) to 11.7 (median; 7.6-22.7 interquartile range (IQR), n = 6) pmol/lung depending on the different formulations used. Myriocin was also measured in retinas of mice treated by intravitreal injection and ranged from 0.045 (less than the limit of detection) to 0.35 pmol/retina.

Chemical and biological evaluation of Hypericum maculatum Crantz essential oil.

The chemical composition and the antimicrobial activity of the essential oil isolated from the aerial parts of Hypericum maculatum Crantz were determined. In total, 109 compounds were identified, with germacrene D (21.5%), nonane (6.5%), (E)-ß-farnesene (5.3%), δ-cadinene (4.5%), and ledol (4.4%) as the main constituents. The chemical compositions of this oil and of four previously studied H. maculatum oils were compared using multivariate statistical analyses, viz., agglomerative hierarchical cluster and principal component analyses. Based on the results, the interrelationship among the hitherto studied H. maculatum oil samples, including the oil characterized here, was discussed. The study of the antimicrobial potential of the oil against five bacterial and two fungal strains showed that the oil had mainly moderate antimicrobial effects.

Chemical composition and antimicrobial activity of the essential oil of Stachys officinalis (L.) Trevis. (Lamiaceae).

Characterization by GC-FID and GC/MS analyses of the Stachys officinalis (L.) Trevis. essential oil obtained by hydrodistillation of the aerial parts allowed the identification of 190 components that represented 97.9% of the total oil content. The main constituents identified were germacrene D (19.9%), ß-caryophyllene (14.1%), and α-humulene (7.5%). Terpenoids were by far predominant (89.4%), with sesquiterpene hydrocarbons (69.1%) and oxygenated sesquiterpenes (14.8%) being the most abundant compounds detected in the oil. Based on the present and previously published results, multivariate statistical comparison of the chemical composition of the essential oils was performed within the species. Principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) of the data on the volatile profiles of S. officinalis taxa revealed no pronounced differences among the samples originated from the Balkan Peninsula. Additionally, the oil was screened for in vitro antibacterial and antifungal activity using the broth microdilution assay. The oil's best antimicrobial activities were obtained against the mold Aspergillus niger (minimal inhibitory (MIC) and minimal fungicidal (MFC) concentrations of 2.5 and 5.0 mg/ml, resp.) and the yeast Candida albicans (MIC and MFC of 5.0 mg/ml).

Chemical composition and antioxidant and antimicrobial activities of essential oil of Allium sphaerocephalon L. subsp. sphaerocephalon (Liliaceae) inflorescences.

BACKGROUND: Allium sphaerocephalon is a wild-growing plant commonly used as an onion substitute. In this study the essential oil obtained from A. sphaerocephalon subsp. sphaerocephalon inflorescences was analysed by gas chromatography and gas chromatography/mass spectrometry and also evaluated for in vitro antioxidant and antimicrobial activities. The obtained results are reported for the first time and discussed with respect to the sulfur compounds detected in the essential oil. RESULTS: Ninty-one compounds were identified, representing 91.6% (w/w) of the total oil. Major constituents of the analysed sample were shyobunol (15.3%), ß-caryophyllene (8.1%), α-cadinol (7.8%), 3,5-diethyl-1,2,4-trithiolane (isomer II, 5.9%) and δ-cadinene (5.2%). The diluted oil had an antioxidant capacity of 160 000 ± 111 micromol α-tocopherol acetate equivalents g(-1). Its antimicrobial activity was evaluated against five bacterial and two fungal strains using the broth microdilution assay. Among the micro-organisms tested, the most susceptible strains were Pseudomonas aeruginosa (minimal inhibitory/bactericidal concentration = 0.08/2.5 mg mL(-1)) and Aspergillus niger (minimal inhibitory/fungicidal concentration = 0.31/0.63 mg mL(-1)). CONCLUSION: The results showed that the examined species had strong antioxidant and antimicrobial properties and are in accordance with the popular use of plants belonging to the genus Allium in traditional medicine, emphasising the necessity of further detailed study of the active principles in Allium species.