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C18H21NO4, orthorhombic, C2221 (no. 20), a = 10.6891(2) Å, b = 11.8375(2) Å, c = 25.4410(4) Å, V = 3219.11(10) Å3, Z = 8, R gt(F) = 0.0483, wR ref(F 2) = 0.1449, T = 295 K.

Herein, comprehensive data of NMR, MS, IR, and gas chromatography (RI) obtained by GC-MS on commonly used capillary columns of different polarity (non-polar DB-5MS and polar HP-Innowax) of a series of esters of all constitutional isomers of hexanoic acid with a homologous series of ω-phenylalkan-1-ols (phenylmethanol, 2-phenylethanol, 3-phenylpropan-1-ol, 4-phenylbutan-1-ol, and 5-phenylpentan-1-ol) and phenol, in total 48 chemical entities, were collected. The created synthetic library allowed the identification of a new constituent of the P. austriacum essential oil (3-phenylpropyl 2-methylpentanoate). The accumulated spectral and chromatographical data, as well as the established correlation between RI values and structures of regioisomeric hexanoates, provide (phyto)chemists with a tool that will make future identification of related natural compounds a straightforward task.

C17H14N2O3S, monoclinic, P21/c (no. 14), a = 9.8966(5) Å, b = 9.4360(4) Å, c = 16.7115(7) Å, β = 92.245(4)°, V = 1559.39(12) Å3, Z = 4, R gt(F) = 0.0358, wR ref(F 2) = 0.1013, T = 170 K.

BACKGROUND Clinopodium thymifolium is an aromatic plant species that is widespread in the Mediterranean region. It has been considered as a condiment and is used in cooking. As a promising spice plant, some efforts are being made to introduce this plant as a new crop species and it has been successfully cultivated in northern Italy. RESULTS Essential oils isolated from the aerial parts of a flavoring species C. thymifolium were analyzed by gas chromatography and gas chromatography/mass spectrometry. The results of a detailed analysis of the chemical composition of the oils showed the domination of pulegone, piperitone, piperitenone and isomenthone, as well as a significant alteration of the pulegone/isomenthone ratio with the developmental stage of the plant. Additionally, a comprehensive chemical analysis of the oils in combination with detailed spectral analyses and chemical synthesis of selected compounds has led to the identification of two new natural products: isomenthyl formate and neomenthyl 2-methylbutanoate. CONCLUSION The observed chemical variability at the intrapopulation level appeared to be a phenological variation. In an evolutionary sense, the alteration of the pulegone/isomenthone ratio suggests their possible role in the ecological adaptation of the species to pollinators. Significant quantitative changes in the chemical composition of the oil at different phenological stages may be relevant in the case of plant material intended for edible purposes. © 2021 Society of Chemical Industry.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy affecting residents of rural farming areas in many Balkan countries. Although it is generally believed that BEN is an environmental disease caused by multiple geochemical factors with much attention on aristolochic acids (AAs), its etiology remains controversial. In this study, we tested the hypothesis that environmental contamination and subsequent food contamination by polycyclic aromatic hydrocarbons (PAHs) and phthalate esters are AA toxicity factors and important to BEN development. We identified significantly higher concentrations of phenanthrene, anthracene, diethyl phthalate (DEP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBP) in both maize and wheat grain samples collected from endemic villages than from nonendemic villages. Other PAHs and phthalate esters were also detected at higher concentrations in the soil samples from endemic villages. Subsequent genotoxicity testing of cultured human kidney cells showed an alarming phenomenon that phenanthrene, DEP, BBP, and DBP can interact synergistically with AAs to form elevated levels of AA-DNA adducts, which are associated with both the nephrotoxicity and carcinogenicity of AAs, further increasing their disease risks. This study provides direct evidence that prolonged coexposure to these environmental contaminants via dietary intake may lead to greater toxicity and accelerated development of BEN.

L-Glutamic acid decarboxylase (GAD) is an enzyme that ensures the balance between the levels of two neurotransmitters, γ-aminobutyric acid (GABA) and L-glutamic acid (L-Glu), necessary for proper brain functioning. A reduction in the concentrations of GABA and/or GAD activity has been implicated in the symptoms associated with epilepsy, which could be plausibly alleviated by the application of GAD activators. As any unnecessary interference in GAD catalytic activity could be detrimental, it is important to study whether CNS (or other) drug candidates act on GAD or not. The ability to identify and reduce this risk early could significantly improve the process of drug development. Although many methods for measuring GAD activity in various biological samples have been described, only few (such as manometric and radiometric) were adopted as in vitro assays for the screening of potential GAD inhibitors/activators. However, these methods require specialized equipment and/or an expensive radiolabeled substrate, and may have sensitivity and/or reliability issues. Therefore, this study aimed to develop an HPLC-DAD-based assay that would allow a simple and more accurate measurement of GAD inhibition or activation using unpurified mice or rat brain homogenates. This assay is based on the quantification of GABA, formed during the enzymatic reaction, after its derivatization with dansyl chloride. Various parameters were evaluated to optimize the assay procedure (e.g. homogenate volume, incubation time, DMSO content, GAD, GABA, and dansyl-GABA stabilities). This assay was validated for pharmacological screenings using 3-mercaptopropionic acid and gallic acid and GAD obtained from different experimental animals.

2,6-Cyclocuparan-3-ols are chemical markers and major volatiles of several liverwort species. Conflicting reports on the structures of these cyclocuparanols can be found in the literature-different research groups assigned the same spectral data to different structures, yet these inconsistencies were never addressed, let alone satisfactorily explained. Following the isolation of all four diastereoisomeric cyclocuparanols from Marchantia polymorpha, their relative and absolute configurations were extensively studied by chemical and spectroscopic methods and definite stereostructures were proposed.

Both oxidative and psychological (mental) stress are the likely culprits for several acute and chronic health disturbances, and adequate tests mimicking that are needed. Herein, in controlled laboratory surroundings, a PEBL (Psychology Experiment Building Language) test battery was used to evoke stress-related biological responses followed by tracking changes in saliva parameters. The study objectives were to determine the impact of psychological stress on selected salivatory parameters and to assess the correlation between the determined oxidative and stress parameters. The study was conducted on 36 healthy young subjects, mainly females ( n = 24 ). Before and following the completion of a battery of four PEBL tests, subjects’ saliva samples were collected. Stress-evoking changes in total antioxidant capacity and nitrite/nitrate levels, as oxidative stress parameters, and cortisol and immunoglobulin A (IgA), as parameters of psychological stress, were established and mutually correlated by comparing the values of the evaluated parameters pre- and post-PEBL test. The results showed that there is no change in the total salivary antioxidant capacity ( p > 0.05 ); however, there was a significant increase in nitrites/nitrates levels after the PEBL test ( p = 0.007 ). On the other hand, the determined cortisol levels after the test battery were found to be statistically significantly increased ( p = 0.025 ) when compared to the values obtained before the test, while the levels of IgA were found to be statistically significantly decreased ( p < 0.001 ). The only statistically significant correlation between the changes in the studied parameters was found to be the one between cortisol and IgA levels (Spearman’s Rö = -0.4). These results suggest that the short-term stress induced by the PEBL test does evoke changes in the salivary mental stress-related parameters (an increase in cortisol and nitrite/nitrate levels, and a decrease in IgA), but not in the total antioxidant capacity. They also indicate that the constructed PEBL four-test battery might represent an adequate laboratory stress-inducing paradigm.

In this investigation, chromatographic separations of the diethyl ether extracts of two European annual Bupleurum taxa, B. praealtum and B. veronense, yielded nine new natural products, namely, a series of esters of stereoisomeric tetradeca-5,7,9,11-tetraen-1-ols (1-4 and 8), a tetra-unsaturated γ-tetradecalactone (5), a dibenzylbutyrolactone lignan (7-oxoarcitin, 6), a falcarinol-related 17-membered macrolide (7) possessing a conjugated diyne-system, and an acylphloroglucinol derivative (9). All these new compounds were fully characterized by NMR, IR, UV, MS, and optical rotation measurement, including 1H NMR full spin spectral simulation, whereas the absolute configurations of 1, 5, and 9 were determined via chemical correlations and NMR analysis of Mosher esters. The in vitro potential immunomodulatory activities of 1, 4, 5, and (+)-arcitin were assessed by determining their effects on the functional properties of isolated rat splenocytes and peritoneal macrophages. The results obtained support the known immunomodulatory ethnomedicinal usage of Bupleurum species.

Background: Besides numerous advantages and commodities offered by smartphones, there are obvious unhealthy effects. The global trend of an increase in the frequency of usage of smartphones, that is, prolonged screen time, is closely related to problematic smartphone use. The aim of our study was to measure the level of problematic smartphone use in a student population through the assessment of the smartphone screen time and the determination of the student chronotype, as well as through the correlation between these variables. Methods: The participants were students of medicine of both sexes. Problematic smartphone use was measured by the short version of the Smartphone Addiction Scale. Smartphone screen time was assessed by the free Android application Quality Time. Chronotype was established by the Morningness-Eveningness Questionnaire. Results: Almost one quarter (22.7%) of students involved in our study could be classified as being “smartphone-addicted”. The students with problematic smartphone use more frequently (statistical significance) belonged to the evening chronotype. Those students spent significantly more time on their phones compared to the non-addicted ones. There was no statistically significant difference between the number of male and female students with problematic smartphone use. The best predictors of problematic smartphone use were longer daily smartphone screen time and evening chronotype personality. Conclusions: The results of our study showed that a significant number of students of medicine showed problematic smartphone use. There was a strong correlation between extensive screen time and the level of problematic smartphone use in the studied population.

Introduction Minor plant constituents are difficult to identify due to the challenging isolation and acquiring of reliable spectral data. Essential oils abound in such minor constituents that might be of high importance for their (e.g. olfactory) properties. The presence of new minor constituents is usually inferred from gas chromatography mass spectrometry (GC-MS) analyses that provide only a mass spectrum and retention data, which are insufficient to allow a positive identification. Objective To identify a minor unknown constituent of the essential oil of Achillea abrotanoides (Vis.) Vis. (Asteraceae). Methodology The application of chemical transformations (oxidation and reduction) performed directly on crude essential-oil samples, followed by preparative chromatography and detailed spectral analysis, to identify a new longipinane ketone from the mentioned sample. Results GC-MS analyses of the essential oil revealed, among other constituents, the presence of a known rare longipinane alcohol (α-longipinen-7β-ol) representing 2.5% of the total GC-peak areas, and a related unidentified oxygenated sesquiterpene (3.8%). Interpretation of their mass spectra led to an assumption that the unidentified one could represent α-longipinen-7-one. Oxidation of the entire essential-oil sample by pyridinium chlorochromate confirmed the assumed relationship among the compounds and gave a simplified enriched mixture containing the ketone (ca. 16%). A straightforward chromatographic separation of the ketone was followed by corroboration of its structure by nuclear magnetic resonance (NMR) (one- and two-dimensional), infrared (IR) and MS. Conclusions The complementing use of chemical transformations of crude essential oils, chromatographic separations, and detailed spectral analysis could have a more general application in the identification of new natural products.

Anxiety is an inborn emotional and cognitive reaction that enables humans to cope with everyday situations, however, it can be pathological as well. Although Spielberger's State-Trait Anxiety Inventory (STAI) scales are most frequently used to study the presence/absence of anxiety, there is a lack of empirical studies in Serbian healthy and/or diseased population that would indicate its reliability and validity. The aim of the present study was to determine some normative values for STAI scales (state and trait) and to determine its reliability and validity in the studied population of university students and psychiatric patients. Score values obtained from the two analyzed samples, which did not show a normal distribution, showed to be statistically significantly different. Receiver operating characteristic curve analysis revealed that values of area under the curve for the two scales were > 0.85 (p < 0.001) and cut-off values suggested that the presence of anxiety was determined to be 38.5 for the S-scale and 45.5 for the T-scale. Data analysis revealed, according to the intraclass correlation coefficient, that S-scale had a moderate reliability (Cronbach Alpha = 0.713) and that T-scale had a good reliability (Cronbach Alpha = 0.858). Also, STAI scales given to patients suffering from anxiety disorders were determined to measure the presence of anxiety with coefficient Alpha higher than 0.9. The calculated validity, internal consistency, and reliability for the translated STAI version are satisfactory, meaning that the usage of the translated STAI can clearly measure the changes in the level of anxiety in patients suffering from neurotic, stress-related, and somatoform disorders.

Glucosinolates are abundant in plants of the order Brassicales, and they are degraded by myrosinases into various organic breakdown products: isothiocyanates, thiocyanates, nitriles, etc., depending on their structure, conditions of hydrolysis, the presence of certain protein cofactors. Their most common hydrolysis products are isothiocyanates, while simple nitriles, epithionitriles, and thiocyanates are produced occasionally. Organic thiocyanates are described from a very limited number of Brassicales taxa. Up to now benzyl, (4-hydroxyphenyl)methyl, (4-methoxyphenyl)methyl, 4- methylthiobutyl, and allyl thiocyanates were reported as products of glucosinolates autolysis. The present review summarizes the knowledge on the mechanism of organic thiocyanate formation from the corresponding thioglucosides. The enzymatic formation of organic thiocyanates is believed to be enabled by thiocyanate-forming protein (TFP), but they could be formed via metabolic routes that do not involve TFP. All of the reported thiocyanates are produced from stable (carbo)cationic species that allow an isomerization of an isothiocyanate to thiocyanate, and vice versa. Although the possibility that thiocyanates can be biosynthesized in plats under certain conditions cannot be dismissed, allyl thiocyanate can be a thermal isomerization artefact of the original isothiocyanate that is formed in the heated zones of the gas chromatograph, while other thiocyanates could form in an aqueous medium via heterolytic dissociation to ambident nucleophilic SCN- and its recapture. One should always be aware of this analytical shortcoming when concluding on the presence and quantity of these specific (iso)thiocyanantes in the analyzed sample.

To complement the knowledge on the anti-inflammatory activity of methyl and isopropyl N -methylanthranilates, two natural products with panacea-like properties, we investigated their effects on thioglycolate-elicited macrophages by evaluating macrophage ability to metabolize MTT, macrophage membrane function, and macrophage myeloperoxidase and phagocytic activities. Moreover, two additional aspects of the inflammatory response of these compounds, their inhibitory activity on xanthine oxidase and catalase, were studied. It was found that these two compounds regulate elicited macrophage functions, most probably by interfering with the function of cell membranes and changing the reducing cellular capacity or enzyme activity of macrophages. Nonetheless, no significant inhibitory action either towards xanthine oxidase or catalase was found, suggesting that the inhibition of these enzymes is not involved in the anti-inflammatory mode of action of these two esters.

Epileptic seizures are a consequence of uncontrolled neuronal discharge and demand urgent and prolonged treatment. Due to a lack of potent and low-risk drugs that could prevent seizures, efforts are underway to discover new drugs, and plant metabolites are often considered valuable candidates in this search. Lemon balm ( Melissa officinalis L., Lamiaceae) is a world-renowned medicinal plant affecting central nervous system function. In this study, we aimed to examine whether the results from in silico modeling of the interactions of major lemon balm essential oil constituents with GABAA and glycine receptors correspond to in vivo results of the convulsions in mice induced by the application of either pentylenetetrazol (GABAA antagonistic) or strychnine (glycine receptor antagonist). While molecular docking experiments of essential oil constituents to the two receptors demonstrated the possibility of ligand–receptor interactions, no binding poses were scored highly, and as the in vivo effect of the essential oil on convulsions seems to be only moderate, the results of the in silico study seem not to contradict results obtained by in vivo models. Thus, we can say that molecular docking might be a useful tool in initial screening for active constituents of natural product mixtures and the potential prediction of their activity in models in vivo.

Herein n-, iso- and anteiso-series of very-long-chained (VLC) alkanes (C21 -C35 ), fatty acid benzyl esters (FABEs; C20 -C32 ), and 2-alkanones (C23 -C35 ) were identified in the wax of Primula veris L. and P. acaulis (L.) L. (Primulaceae). For the very first time in a sample of natural origin, the presence of iso- and anteiso-VLC FABEs and 2-alkanones was unequivocally confirmed by synthetic work, derivatization, and NMR. It should be noted that the studied species produced unusually high amounts of branched wax constituents (e. g., >50 % of 2-alkanones were branched isomers). The domination of iso-isomers, probably biosynthesized from leucine-derived starters, is a unique feature in the Plant Kingdom. The plant organ distribution of these VLC compounds in P. acaulis samples (different habitats and phenological phases) pointed to their possible ecological value. This was supported by a eutectic behavior of binary blends of FABEs and alkanes, as well as by high UV-C absorption by FABEs.

A recent identification of eugenyl (allylmethoxyphenyl) esters as Anthemis segetalis Ten. (Asteraceae) essential oil constituents, accomplished by means of organic synthesis, motivated us to expand the existing synthetic library with an aim to examine the generality of structure‐chromatographic property relationships within this series of volatiles. Herein, the design, synthesis, gas–chromatographic and spectral characterization of members of a library of 85 allylmethoxyphenyl esters (64 are completely new) were described. Analysis of experimentally obtained RI data showed that esters of the same acid and different allylmethoxyphenols always elute in the same order from an apolar gas chromatography (DB‐5MS) column: 2‐allyl‐6‐methoxyphenyl

Structural elucidation of a new triquinane sesquiterpenoid, presilphiperfolane-7α,8α-diol, 1a, isolated from Pulicaria vulgaris, was accomplished by combining solvent-induced removal of chemical sh...

To better characterize the constituents responsible for the specific odor of Helichrysum italicum subsp. italicum, the key odorants of a sample of commercial essential oil produced industrially were identified by Gas Chromatography-Olfactometry (Aroma Extract Dilution Analysis) (GC-O AEDA). These compounds were characterized, together with 82 constituents, by careful fractionation procedures and Gas Chromatography-Mass spectrometry and GC-O analyses applied to the entire oil and to its fractions. Several authentic samples of reference constituents (purchased commercially or synthesized by original procedures) were co-injected to confirm some identifications. The most odor-active constituents perceived by all the panelists and showing the highest mean Flavor Dilution factor were 4,6-dimethyloctan-3,5-dione, 1,8-cineole and nerol. Many other constituents in low or, even, in trace amounts, also participate to the global odor of the essential oil.

We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.

Carvacrol (5-isopropyl-2-methylphenol) is a biologically active monoterpene phenol abundantly present in the essential oils of many Lamiaceae aromatic/ethnomedicinal plants. Herein, we aimed to evaluate the damaging effect of carvacrol to rat pancreatic tissue, but also to assess its possible ameliorative impact on pancreatic damage induced by L-arginine. The toxic and beneficial (in a dose of 10 mg/kg) properties of carvacrol were assessed by measuring serum α-amylase and lipase activities, tissue malondialdehyde (MDA) content, and pathohistological changes in pancreatic tissue. Application of 100/500 mg/kg of carvacrol produced a significant increase in α-amylase activity, followed by inflammatory-cell infiltration and patchy interlobular edema in the pancreas. In the L-arginine-induced pancreatitis model, a dose of 10 mg/kg of carvacrol prevented an increase in α-amylase and lipase activities, and MDA formation, when compared to the animals that received L-arginine only. Animals treated with carvacrol prior to L-arginine administration displayed mild edema and inflammatory infiltration with few necrotic areas. Contrary to that, animals that received only L-arginine showed a massive leukocyte infiltrate with edema and substantial necrotic areas. In our study carvacrol showed significant protective effects and a potential to modulate leukocyte recruitment in pancreatic tissue after L-arginine injection.

The toxicity of natural marine iodoarenes or their synthetic counterparts is widely unknown despite the fact that triiodothyronine and thyroxine are members of this class. In this work we aimed to expand such knowledge on iodinated marine natural products and tested an ascidian (Didemnum rubeum) metabolite, N-(3,5-diiodo-4-methoxyphenethyl)benzamide, together with closely related synthetic iodinated tyramides: N-(2,5-diiodo-4-methoxyphenethyl)benzamide, N-(3-iodo-4-methoxyphenethyl)benzamide, N-(4-methoxyphenethyl)benzamide, and N-(3-iodo-4-methoxyphenethyl)formamide, for their effect on the viability of rat macrophages, as well as acute toxicity on Artemia salina. The tested tyramides exerted a varying degree of toxicity towards brine shrimps, but in certain cases, the determined lethal concentrations were even lower than those of known toxicants (e.g. strychnine sulfate, SDS). The toxicity was highly dependent on the structure of these mutually related compounds, while the natural one was shown to be the most toxic. In the case of macrophage cultures, the tested tyramides exerted much less toxicity but were found to have an effect on the functioning of these normal immune cells. The samples of the tyramides were obtained by synthesis, and were fully structurally and spectrally characterized, which also provided corroboration of the proposed structure of the natural product originally isolated in minute amounts.

The aim of the study was to analyze the characteristics {sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and credibility} of tests for microbiological diagnosis of infections caused by Clostridium (C. difficile). The research was done at the Public Health InstituteNiš, the Center for Microbiology during the period 2016-2019. The study included 25 patients with Clostridium difficile infection (CDI) (25 fecal samples) and 50 patients with diarrhea who were not diagnosed with CDI (50 faecal samples). The samples were examined by various tests for the detection of toxin in the stool and with two tests to prove the produced glutamate dehydrogenase enzyme - GDH. RIDA GENE Clostridium difficile test (Real Time Multiplex PCR, R-Biofarm, Damstadt, Germany) was used as a reference test. Among the examined tests, the highest sensitivity in toxin detection was the ELISA-ridascreen C. difficile Toxin A / B (R - Biopharm AG, Darmstadt, Germany) (88%, PPV = 85.71%, NPV = 97.87%) and the lowest C. difficile TOXIN A& B - CHEK-1 (VEDALAB, ALENCON CEDEX, France) (68%, PPV = 85%, NPV = 85.45%). All toxin detection tests had a high specificity that was not less than 92%. In detecting the GDH antigen, the Rida®QUICK C. difficile GDH test (R - Biopharm AG, Darmstadt, Germany) showed better performance (sensitivity 100%, specificity 92%, PPV = 89.28%, NPV = 100% and authenticity 94.66% ). The results of the research conducted in Niš showed high values of the characteristics for certain toxindetecting tests in feces (sensitivity up to 88%, specificity to 98%, etc.). Research results in other studieshave shown that the values of the parameters that determine the characteristics of the tests are lower by 10% - 20%, although there is a study whose results are consistent with ours. The reasons for relatively high values should be sought in strict selection criteria for samples that are close to criteria present in factory conditions when designing such tests.

Previously 3 sesquiterpenoids from Conocephalum conicum (L.) Dum. (Conocephalaceae) were found to modulate lymphocyte response to different stimuli, suggesting their immunomodulatory potential. Herein we evaluated the impact of low concentrations of these sesquiterpenoids on rat splenocyte viability and membrane permeability, as well as lactate dehydrogenase (LDH) activity, in order to, possibly, shed light on their mechanism of action. After a 24 h incubation of splenocytes with the sesquiterpenoids (from 10−8 to 10−6 M), MTT and trypan blue (TB) assays, as well as histochemical staining for LDH, were performed. The tested compounds were shown not to reduce the ability of cells to metabolize MTT; however, cell membrane permeability to TB was altered, suggesting that a certain percentage of cells were dead. Histochemical staining for LDH presence releveled that only 2, out of the 3 sesquiterpenoids, decreased the staining intensity, indicating either LDH leakage or its inhibition. In conclusion, having in mind the already proven modulatory potential of the tested sesquiterpenoids, the present results suggest that through the changes in the cell membrane function and leakage/inhibition of LDH in unaltered immune cells, some of the tested compounds could be considered promising candidates for further research as anticancer agents.

The oil extracted from hemp seeds has significant nutritional and biological properties due to the unique composition of polyunsaturated fatty acids and various antioxidant compounds. The potential of this oil for the prevention of oxidative stress and for the treatment of oxidative-stress-induced ailments is of increasing interest. Most studies of hemp seed oil were conducted in-vitro, meaning we lack information about effects and activity in vivo. In the present study, we evaluated the hypothesis that hemp seed oil at different concentrations improves the oxidative state of D. melanogaster, under non-stress as well as hydrogen-peroxide-induced stress. We analyzed the effects of hemp seed oil on oxidative stress markers and on the life cycle of D.&nbsp, melanogaster under non-stress and hydrogen-peroxide-induced stress conditions. D.&nbsp, melanogaster larvae were exposed to hemp seed oil concentrations ranging from 12.5 to 125 μL/mL. The results revealed that under non-stress conditions, oil concentrations up to 62.5 µL/mL did not induce negative effects on the life cycle of D. melanogaster and maintained the redox status of the larval cells at similar levels to the control level. Under oxidative stress conditions, biochemical parameters were significantly affected and only two oil concentrations, 18.7 and 31.2 µL/mL, provided protection against hydrogen peroxide stress effects. A higher oil concentration (125 μL/mL) exerted negative effects on the oxidative status and increased larval mortality. The tested oil was characterized chemically by NMR, transesterification, and silylation, followed by GC-MS analyses, and was shown to contain polyunsaturated fatty acid triglycerides and low levels of tocopherols. The high levels of linoleic and linolenic acids in the oil are suggested to be responsible for the observed in vivo antioxidant effects. Taken together, the results show that hemp seed oil is effective for reducing oxidative stress at the cellular level, thus supporting the hypothesis. The obtained results point to the potential of hemp seed oil for the prevention and treatment of conditions caused by the action of reactive oxygen species.

Inflammatory bowel diseases (IBM), such as Crohn's disease, and their common complications represent a global health challenge. Many pyrazole derivatives, such as the spasmolytic drug metamizole, have already found their place among the frequently used therapeutic agents. Alteration of the structure of established therapeutic drugs by introducing a ferrocene moiety was shown to be a promising way for the discovery of new drugs. Herein, two libraries of analogous ferrocenyl (1a-1j) and phenyl alkanols (2a-2j) containing a pyrazole core, among which 17 completely new structures, have been synthesized, and structurally and electrochemically characterized. These compounds, along with the aldehydes used for their synthesis, were tested in parallel for their antispasmodic, acetylcholinesterase-inhibitory, and antimicrobial activities to evaluate their potential as multitarget IBM drugs. The antispasmodic activity was investigated by assessing their effect on both the amplitude and number of spontaneous contractions of isolated rat ileum. Their antimicrobial effect was evaluated against a panel of Gram-positive and Gram-negative bacterial strains and fungi. It was found that several of the evaluated compounds displayed gastrointestinal smooth muscle relaxant activity, among them, 1-(1H-3-ferrocenyl-1-phenylpyrazol-4-yl)-3-methylbutan-1-ol (1d) showed a remarkable effect by superseding the activity of papaverine. Together with the fact that it represents one of the most antimicrobially active investigated compounds, 1d is a good candidate for further pharmacological evaluation as a multitarget drug for IBM. © 2021 John Wiley & Sons, Ltd.

GC, GC/MS and NMR analyses of Scilla bifolia washings allowed for the identification of thirty-six long-chain compounds belonging to six homologous series (five of which are from the class of resorcinols, a group of biologically important phenols): 1-alkyl-3,5-dimethoxybenzenes, 5-alkyl-3-methoxy-2-methylphenols, 3-alkyl-5-methoxyphenols, 5-alkyl-2-methylresorcinols (five compounds from each of the series); 5-alkylresorcinols (six compounds) and 1,3-alkanediols (ten compounds). Many of these compounds rarely occur in Nature. Retention indices of these compounds, as well as indices of the corresponding trimethylsilyl derivatives, were reported, some of them for the first time. The exact regiochemistry was unambiguously determined by two-dimensional NMR experiments; in some cases, the complete NMR assignment was augmented by computer spin-simulation of 1 H-NMR spectra.

Structural elucidation of three new sesquiterpenoids, namely, (1

Thirteen commercial essential oils were assessed for their possible inclusion in a mouthwash formulation based on their inhibitory effect against potentially pathogenic anaerobic oral bacterial isolates from subgingival plaque, and their cytotoxicity towards gingival cells. The essential oils, originating from species belonging to seven major aromatic plant families, were chosen to provide the necessary diversity in chemical composition that was analyzed in detail by GC and GC/MS. Multivariate statistical analysis, performed using the in vitro microbiological/toxicological assays and compositional data, revealed that the major components of the essential oils were probably not the main carriers of the activities observed. A formulation of 'designer' mouthwashes is proposed based on the selective action of certain essential oils towards specific bacterial isolates (e. g., Citrus bergamia vs. Parvimonas micra), and non-toxicity to gingival cells at antimicrobially active concentrations.

In this work, we explored the possible polypharmacological potential of the already established antimicrobials against gastrointestinal pathogens, 4-(alkylamino)-3-nitrocoumarins, as antianxiety agents, using a battery of in vivo experiments. Three chosen coumarin derivatives, differing in the substituent (sec-butylamino, hexadecylamino, or benzylamino) at position 4, at the doses of 25, 50 and 100 mg kg-1 , were evaluated in light/dark, open-field, horizontal wire and diazepam-induced sleep models using male BALB/c mice. Depending on the applied dose, all three tested coumarins displayed a noteworthy anxiolytic-like effect. 4-(sec-Butylamino)-3-nitro-2H-chromen-2-one and 4-(hexadecylamino)-3-nitro-2H-chromen-2-one could be recognized as true anxiolytics in the lowest applied dose, based on three tests, without exerting any sedative effects. Thus, the 3-nitrocoumarin core deserves further chemical diversity exploration in the 'antianxiety' direction.

Using the "chiral pool" approach, two modified total syntheses of the biologically active δ-lactone cleistenolide (1) have been achieved starting from d-glucose. These approaches also enabled the preparation of novel analogues and derivatives of natural product 1. The applied strategy for the synthesis of 1 involves: the initial degradation of the chiral precursor for a single C-atom, C2-fragment chain extension using Z-selective Wittig reaction, and the final δ-lactonization. All tested cleistenolide analogues displayed antimicrobial activity against a panel of nine microbial strains, most of them superseding the activity of cleistenolide itself, and, in some cases, coming close in value to the observed minimal inhibitory concentrations of chloramphenicol. Increased lipophilicity of the derivatives and the non-sterically congested conjugated lactone moiety were a prerequisite for analogues with high inhibitory activity against S. aureus and, in general, Gram-positive bacteria.

Helichrysum italicum (immortelle) is a dwarf aromatic shrub native to the Mediterranean region. The typical subspecies (italicum) produces an essential oil rich in neryl acetate and characteristic β-diketones, italidiones, highly valued in the perfume industry. As esters are an important group of aroma-active volatiles, herein the composition of the ester fraction of this immortelle chemotype essential oil was studied in detail. Chromatographic separation of Corsican immortelle essential oil enabled the discovery of numerous potentially olfactory-interesting esters of nerol and/or angelic acid, undetectable by direct GC-MS analyses of the unfractioned oil. Four esters of nerol and medium-chain branched fatty acids represent new natural products, while several other esters have a rather restricted occurrence in the Plant Kingdom.