Exploring the Antimicrobial Properties of 99 Natural Flavour and Fragrance Raw Materials against Pathogenic Bacteria: A Comparative Study with Antibiotics.

Currently, one of the most serious global problems is the increasing incidence of infectious diseases. This is closely related to the increase in antibiotic use, which has resulted in the development of multidrug resistance in microorganisms. Another problem is the numerous microbiological contaminations of cosmetic products, which can lead to dangerous bacterial infections in humans. Natural fragrance raw materials exhibit a wide spectrum of biological properties, including antimicrobial properties. Despite their prevalence and availability on the commercial market, there is little research into their effects on multidrug-resistant microorganisms. This study examines the inhibitory effect of natural substances on Gram-positive and Gram-negative bacteria. For this purpose, screening and appropriate assays were carried out to determine the minimum inhibitory concentration (MIC) value of individual substances, using the alamarBlueTM reagent. The lowest MIC values were observed for Staphylococcus aureus (black seed (Nigella sativa) expressed oil, MIC = 25 µg/mL), Kocuria rhizophila (fir balsam absolute, MIC = 12.5 µg/mL), and Pseudomonas putida (cubeb oil and fir balsam absolute, MIC = 12.5 µg/mL). The most resistant Gram-negative species was Enterobacter gergoviae, while Staphylococcus epidermidis was the most resistant Gram-positive species.

Evaluation of the anti-SARS-CoV-2 properties of essential oils and aromatic extracts.

Essential oils and aromatic extracts (oleoresins, absolutes, concretes, resinoids) are often used as food flavorings and constituents of fragrance compositions. The flavor and fragrance industry observed significant growth in the sales of some natural materials during the COVID-19 outbreak. Some companies worldwide are making false claims regarding the effectiveness of their essential oils or blends (or indirectly point toward this conclusion) against coronaviruses, even though the available data on the activity of plant materials against highly pathogenic human coronaviruses are very scarce. Our exploratory study aimed to develop pioneering knowledge and provide the first experimental results on the inhibitory properties of hundreds of flavor and fragrance materials against SARS-CoV-2 main and papain-like proteases and the antiviral potential of the most active protease inhibitors. As essential oils are volatile products, they could provide an interesting therapeutic strategy for subsidiary inhalation in the long term.

Cytotoxicity, early safety screening, and antimicrobial potential of minor oxime constituents of essential oils and aromatic extracts.

Due to market and legislative expectations, there is a constant need to explore new potential antimicrobial agents for functional perfumery. In this study, we evaluated the antimicrobial activity of 53 low molecular oximes and the corresponding carbonyl compounds against Escherichia coli, Enterococcus hirae, Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus, Aspergillus brasiliensis, Legionella pneumophila and Candida albicans. The most potent compound was α-isomethylionone oxime, which exhibited a minimum inhibitory concentration (MIC) of 18.75 µg/mL against E. hirae. The evaluation of the MICs for bacterial and fungal strains was performed for selected compounds, for example, the MIC of 2-phenylpropionaldehyde, cis-jasmone oxime, and trans-cinnamaldehyde measured against A. brasiliensis was 37.50 µg/mL. ADME-Tox (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assays were performed to assess the cytotoxicity of tested compounds. ADME-Tox indicated the safety and promising properties of selected compounds, which enables their usage as nontoxic supporting antibacterial agents. The results of the in vitro MTS assay were consistent with the ADME-Tox results. None of the compounds tested was toxic to Human Embryonic Kidney 293T (HEK293T) cells, with all cell viabilities exceeding 85%.

Minor constituents of essential oils and aromatic extracts. Oximes derived from natural flavor and fragrance raw materials - Sensory evaluation, spectral and gas chromatographic characteristics.

A small library of 57 low molecular weight oximes was prepared from fragrant aldehydes and ketones, and their olfactory profiles were determined. The most substantive and interesting in terms of the sensory impressions were (+)-isomenthone oxime (fresh, musty, green) and cyclocitral oxime (earthy with patchouli, moss and leather notes). The linear retention indices (LRI) were determined for DB-1, DB-5 and DB-WAX columns, and E/Z isomers of 22 out of 57 compounds were resolved on the DB-5 column. Attempts were made to resolve enantiomers of the chosen oximes on chiral GC columns. The best results were obtained by using a Cyclosil B column, on which the enantiomers of camphor, menthone, piperitone and carvone oximes were fully resolved. NMR and MS spectra were acquired to characterize the synthesized library. Gas chromatography-olfactometry was used to assess odoriferous properties of both isomers of oximes. In most cases both isomers possessed similar profile and intensity.

Novel Benzene-Based Carbamates for AChE/BChE Inhibition: Synthesis and Ligand/Structure-Oriented SAR Study.

A series of new benzene-based derivatives was designed, synthesized and comprehensively characterized. All of the tested compounds were evaluated for their in vitro ability to potentially inhibit the acetyl- and butyrylcholinesterase enzymes. The selectivity index of individual molecules to cholinesterases was also determined. Generally, the inhibitory potency was stronger against butyryl- compared to acetylcholinesterase; however, some of the compounds showed a promising inhibition of both enzymes. In fact, two compounds (23, benzyl ethyl(1-oxo-1-phenylpropan-2-yl)carbamate and 28, benzyl (1-(3-chlorophenyl)-1-oxopropan-2-yl) (methyl)carbamate) had a very high selectivity index, while the second one (28) reached the lowest inhibitory concentration IC50 value, which corresponds quite well with galanthamine. Moreover, comparative receptor-independent and receptor-dependent structure⁻activity studies were conducted to explain the observed variations in inhibiting the potential of the investigated carbamate series. The principal objective of the ligand-based study was to comparatively analyze the molecular surface to gain insight into the electronic and/or steric factors that govern the ability to inhibit enzyme activities. The spatial distribution of potentially important steric and electrostatic factors was determined using the probability-guided pharmacophore mapping procedure, which is based on the iterative variable elimination method. Additionally, planar and spatial maps of the host⁻target interactions were created for all of the active compounds and compared with the drug molecules using the docking methodology.

Burkholderia cepacia lipase immobilization for hydrolytic reactions and the kinetic resolution of the non-equimolar mixtures of isomeric alcohols.

The major drawbacks of native lipase applications in processes occurring in water or in organic solvents include: difficulties in catalyst recycling, low activity and operational instability. The immobilization of Burkholderia cepacia lipase by adsorption or covalent binding onto 5 differently functionalized carriers (silica, acrylic, cellulose-based) was performed to overcome this problem. The optimization of the reaction preparation in water-rich media was based on the hydrolytic reactivity of the preparations, as well as the thermal, operational and storage stabilities. Aminated silica carrier, activated with glutaraldehyde, was determined to be the carrier of choice. Regarding processes in water-restricted media, carrier selection was based on reactivity after drying and five preparations were chosen for the resolution of a non-equimolar isomer mixture (85:15 ratio of R to S isomers), treating the kinetic resolution of ((+)-(S/R)-1-[(1S,5R)-6,6-dimethylbicyclo[3.1.0]hex-2-en-2-yl)]ethanol as a model. The resulting acetate of R configuration exhibits interesting sensory properties. The operational stability of the chosen catalysts was tested over 15 consecutive batch processes; the most beneficial results were obtained with lipase adsorbed on an acrylic carrier. Conversion increased gradually from 10 to 84% over the first five processes, which could be explained by the product sorption onto the carrier. Full kinetic resolution with maximal substrate conversion (approximately 84%) was achieved and remained stable during the next 10 runs, an excellent result, and thus, the proposed system might be regarded as an exceptionally attractive solution for the perfume and cosmetic industries.

The anxiolytic-like activity of a novel N-cycloalkyl-N-benzoylpiperazine derivative.

BACKGROUND: Anxiety-related disorders are among the most common mental illnesses in the world for which benzodiazepines, buspirone and antidepressant drugs remain the first-line treatment. These drugs have good efficacy but they have numerous disadvantages, such as drug abuse potential, delayed onset of action or tolerance. A literature review reveals that a variety of piperazine derivatives may exhibit interesting pharmacological properties, including anxiolytic-like, antidepressant, nootropic and antinociceptive activities demonstrated in animal models, as well as an antioxidant capacity shown in some in vitro tests. Hence, the aim of this study was the synthesis and preliminary pharmacological in vivo evaluation of a novel N-cycloalkyl-N-benzoylpiperazine derivative, compound 9. METHODS: The test compound 9 was synthesized from a cyclic ketone 6,6-dimethylbicyclo[3.1.0]hexan-3-one (compound 7) and N-benzoylpiperazine. The final product was evaluated in vivo for its anxiolytic-like and antinociceptive activity after intraperitoneal (ip) administration. Its impact on animals' locomotor activity and motor performance was also evaluated. RESULTS: At the dose of 50mg/kg the test compound 9 showed statistically significant (p<0.01) anxiolytic-like activity in the four plate test. This effect was completely abolished by pretreatment with naloxone hydrochloride (1mg/kg; ip). Compound 9 did not influence animals' locomotor activity or motor coordination. No antinociceptive effect was demonstrated in the hot plate test. CONCLUSIONS: The anxiolytic-like properties of N-bicyclo-[3.1.0]hexyl derivative (9) in the four plate test are mediated by the opioid system. The results obtained make this compound a promising lead structure for further development of anxiolytic drugs.