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Humans are exposed to various volatile organic compounds (VOCs) through ingestion, inhalation, or skin contact, potentially leading to adverse health consequences. In this study, the distribution of vari-ous VOCs in indoor air in North Macedonia and Kosovo was investigated for the first time. From March to December 2023, the monthly relative abundance of VOCs was monitored using Radiello® pas-sive/diffusive samplers, followed by gas chromatography mass spectrometry (GC MS) analysis. A total of 60 samples were collected from 17 sites, where over 70 individual VOCs belonging to several classes were identified. Benzene, toluene, ethylbenzene, and xylenes (BTEX) compounds were the most abundant in the chemical stockroom, contributing up to 77.84 % of the total VOC relative abun-dance. In the printing store/workplace, alkylbenzenes were predominant, comprising 69.72 %. Alcohols and ethers were primarily detected in the coffee shop, whereas organosiloxanes were dominant in the hair salon, accounting for 33.87 % and 54.46 % of the total VOCs, respectively. Terpenes were a significant component in the meat factory, representing 65.78 % of the total VOCs, while hydrocarbons were most prevalent in the oil & lubricants store, accounting for 58.23%. Halogenated compounds were primarily found in the superstore, constituting 20.42 % of total VOCs. The VOC composition results indicate that their presence in indoor environments may pose both acute and chronic health risks.

Gas chromatography coupled with mass spectrometry (GC-MS) is a standard analytical method for identifying specific volatile organic compounds (VOCs) in urban air samples. Quantification ideally relies on calibration curves using standards for each compound. However, due to the variable composition of VOCs and the limited availability of all standards, this strategy is challenging and not always feasible. Quantification using an internal standard is a simple and accurate approach, as it involves the simultaneous analysis of the internal standard and analytes, eliminating the need for a calibration curve if their concentrations fall within the linear dynamic range. In this study, quantification of VOCs from different chemical classes has been evaluated using a single standard mixture and anisole as an internal standard and compared to the external calibration as standard method for quantification by GC-MS. Both methods showed comparable results, with a relative error within ±30% of the theoretical concentration. Linearity was confirmed in the range from 100 to 4000 μg/L, and the relative standard deviation (RSD) of the relative response factors (RRFs) met the acceptance criteria of ≤30% for each target VOC. Toluene, chlorobenzene, C6-C2 and C6-C3 substituted benzenes yielded similar average RRFs, ranging from 1.280 to 1.601 with an RSD of 7.83%. The methods were applied for quantification of VOCs in ambient air on real samples collected on Radiello adsorbents at one urban location. Using anisole as an internal standard proved to be a simple and reliable method for determining VOC concentrations, offering a convenient alternative to external standard calibration.

This paper presents a dataset obtained from an RT2-qPCR array analysis of rat pancreatic RIN-m cells treated with two monocarbonyl analogs of curcumin (MACs), C66 and B2BrBC in the presence or absence of streptozotocin (STZ). The array quantified the expression of 84 genes associated with the onset, development, and progression of diabetes. This dataset provides information on the gene expression profiles of pancreatic cells modulated by two specific MACs in a diabetic context. The data can serve as a foundation for developing new hypotheses, designing follow-up experiments, and identifying novel targets for treatment. It can be used to investigate further the molecular mechanisms underlying the therapeutic effects of these MACs and in comparative studies using other experimental antidiabetic compounds.

A monocarbonyl analog of curcumin, (2E,5E)-2,5-bis(2-methoxybenzylidene)-cyclopentanone (B2MBCP), was prepared and characterized via spectroscopic methods (NMR, UV-Vis, FT-IR, and MS). Furthermore, density functional calculations were implemented to study the molecular structure and spectroscopic features, as well as adsorption properties. In addition, Hirshfeld surface and NBO theoretical analysis were carried out. The reduced density gradient (RDG) analysis via non-covalent interactions (NCI) and interaction region indicator (IRI) indicate the presence of extensive Van der Waals interactions. These interactions are classified in different contributions and energy stabilization from Hirshfeld surface analysis where the dominant type of contacts are H···H contacts. The molecular docking studies of B2MBCP with DNA revealed cooperative interactions that led to intercalation. The results from the cyclic voltammetry (CV) measurements agreed with the calculated energies of the frontier orbitals and the compound structure. Theoretical studies indicated that the relatively flat B2MBCP is adsorbed onto a graphene surface, with a significant adsorption energy of –41.19 kcal/mol. The results of this study provide a better overall picture of the properties of MAC with a cyclopentanone core and can be taken as a useful guide in the search for new biologically active compounds and new possible means of delivery.

Abstract Curcumin is a polyphenolic compound derived from turmeric that has potential beneficial properties for cardiovascular and renal diseases and is relatively safe and inexpensive. However, the application of curcumin is rather problematic due to its chemical instability and low bioavailability. The experimental results showed improved chemical stability and potent pharmacokinetics of one of its analogs – (2E,6E)-2,6-bis[(2-trifluoromethyl)benzylidene]cyclohexanone (C66). There are several advantages of C66, like its synthetic accessibility, structural simplicity, improved chemical stability (in vitro and in vivo), presence of two reactive electrophilic centers, and good electron-accepting capacity. Considering these characteristics, we reviewed the literature on the application of C66 in resolving diabetes-associated cardiovascular and renal complications in animal models. We also summarized the mechanisms by which C66 is preventing the release of pro-oxidative and pro-inflammatory molecules in the priming and in activation stage of cardiomyopathy, renal fibrosis, and diabetic nephropathy. The cardiovascular protective effect of C66 against diabetes-induced oxidative damage is Nrf2 mediated but mainly dependent on JNK2. In general, C66 causes inhibition of JNK2, which reduces cardiac inflammation, fibrosis, oxidative stress, and apoptosis in the settings of diabetic cardiomyopathy. C66 exerts a powerful antifibrotic effect by reducing inflammation-related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and CAV-1) and inducing the expression of anti-inflammatory factors (HO-1 and NEDD4), as well as targeting TGF-β/SMADs, MAPK/ERK, and PPAR-γ pathways in animal models of diabetic nephropathy. Based on the available evidence, C66 is becoming a promising drug candidate for improving cardiovascular and renal health.

In order to improve the bioavailability of curcumin, studies have been undertaken to prepare the so-called monocarbonyl analogs of curcumin (MACs) and assess their biological activity. These analogs contain an electrophilic α,β-unsaturated carbonyl moiety (Michael acceptor). Several key biological processes are connected/controlled with thiol alkylation (glutathione, cysteine, cysteine peptide residues). The most likely reaction is the Michael addition between the α,β-unsaturated acceptor and a corresponding thiol. 2,6-Bisarylidenecyclohexanone and 3,5-bisarylidenepiperidin-4-one scaffolds offer convenient tunability of electrophilicity and redox properties of the Michael acceptor by the introduction of various substituents. In this study, several MACs were prepared by Claisen-Schmidt condensation reaction, and their reactivity with 2-(dimethylamino)ethanethiol was evaluated. For this purpose, based on the UV-Vis spectra of the analogs and thiol(s), a proper method for spectrophotometric evaluation of their reactivity with 2-(dimethylamino)ethanethiol was optimized. The relative reactivity of the analogs was 7 > 2 > 5 > 4 > 1 ≈ 6. The developed method is simple, and it can be extended to assess the reactivity of other MACs.

Pyrrolizidine alkaloids (PAs) are secondary plant metabolites, and their 1,2-unsaturated derivatives, which contain the retronecine, heliotridine, or otonecine type of the necine base, have raised concern due to their ability to form hepatotoxic intermediates and exhibit serious toxic effects. Several hundred individual pyrrolizidine alkaloids and their N-oxides have been identified mostly using liquid chromatography coupled with mass spectrometry, although the number of available reference standards is limited. In this work, characteristic fragment ions and their abundance in the mass spectra of different PAs were used to reveal typical fragmentation patterns for various classes of PAs that can be further employed to distinguish monoesters (retronecine, heliotridine type), open chain diesters and macrocyclic diesters, and corresponding N-oxides. Fragment ions at m/z 120 and 138 were found in all types of PAs with a different relative abundance. Additional observation of fragment ions at m/z 94 and 156 was found to be typical for monoester PAs esterified at position C9 of the necin base, whereas fragment ions at m/z 111 and 172 were characteristic for monoester N-oxides. Fragment ions at m/z 180 and 220 were found to be typical for open chain diesters with esterification at C7 with acetic and angelic acid, respectively, whereas fragment ions at m/z 214 and 254 were characteristic for the respective N-oxides. For the 3ʹ-acetyl PA monoester or open chain diester derivatives, characteristic fragment ions were observed after loss of the acetyl moiety ([M+H]+–60), whereas for macrocyclic diesters and their N-oxides, fragment ions due to the neutral loss of CO were found ([M+H]+–28).

Fennel (Foeniculum vulgare Mill.) and anise (Pimpinella anisum L.) are well-known aromatic plants with traditional use as medicinal and culinary spices and herbs. As part of a broader study, the aim of this investigation was to determine the chemical composition of fennel fruit essential oil (Foeniculi fructus aetheroleum, FFA) and anise fruit essential oil (Anisi aetheroleum, AA) and to assess their antimicrobial potential. Hydrodistilled FFA from fruits gathered in central Macedonia was subjected to physico-chemical analysis, as well as commercial AA, which was obtained from a local vendor. The chemical composition of both essential oils was determined using gas chromatography with mass spectrometric detection. The main component of both essential oils was trans-anethole. The antimicrobial action of both essential oils (FFA and AA) was tested against several bacterial cultures and compared to standard antimicrobial agents. The microorganisms used in this research were Gram-positive bacteria (Bacillus pumilus NCTC 8241, Staphylococcus aureus ATCC 6538,), Gram-negative bacteria (Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027), and fungi (Saccharomyces cerevisiae ATCC 9763 and Candida albicans ATCC 10231). The microdilution test enabled determination of the minimal inhibitory concentration (MIC) of all samples used in the experiment against all of the test microorganisms. It was concluded that FFA and AA have moderate antibacterial activity and affect the growth of the Gram positive and the Gram negative bacteria. On the other, they are potent antifungal agents and affect the growth of S. cerevisiae ATCC 9763 and C. albicans ATCC 10231. AA was observed to have a slightly higher antimicrobial activity when compared to FFA. Based on the chemical composition of the samples, a connection was proposed between the trans-anethole content of the essential oils and their antimicrobial properties.

Breast cancer is the most frequently diagnosed life-threatening cancer in women. As a result, there is a critical need for the development of a safe and effective drug therapy for its treatment. Curcumin, a secondary metabolite isolated from Curcuma longa, has been shown to exhibit an impressively broad range of pharmacological effects. Despite its powerful interaction with a diverse set of cellular targets, curcumin has several drawbacks that limit its potential as a therapeutic agent. One of the most common approaches to overcoming these limitations is the design and synthesis of novel curcumin analogs. This study was conducted in support of the ongoing search for new molecules that are effective enough for the treatment of triple-negative breast cancer while causing only minor side effects. Hence, several symmetric monocarbonyl analogs of curcumin with cyclopentanone, cyclohexanone and 4-piperidone as the central core were synthesized via a Claisen–Schmidt condensation reaction. Their structures were identified by measuring the melting points, as well as using FTIR and UV/VIS spectroscopic techniques. To assess the cytotoxic activities of the analogs against MDA-MB-231 breast cancer cells and to identify the significant structural features responsible for these molecules’ potency, combined 2D- and 3D-quantitative structure–activity relationship (QSAR) models were developed. The generated QSAR models demonstrated acceptable internal validation, as well as good external predictive capacity, indicating that they can be used to design similar compounds. These results suggest that the synthesized candidate drugs have promising cytotoxic potential against MDA-MB-231 cancer cells and should be further investigated both in vitro and in vivo.

Abstract Background This study was undertaken to test the hypothesis that the newly synthesized curcuminoids B2BrBC and C66 supplementation will overcome hyperoxia‐induced tracheal hyperreactivity and impairment of relaxation of tracheal smooth muscle (TSM). Materials and methods Rat pups (P5) were exposed to hyperoxia (>95% O2) or normoxia for 7 days. At P12, tracheal cylinders were used to study in vitro contractile responses induced by methacholine (10−8–10−4M) or relaxation induced by electrical field stimulation (5–60 V) in the presence/absence of B2BrBC or C66, or to study the direct relaxant effects elicited by both analogs. Results Hyperoxia significantly increased contraction and decreased relaxation of TSM compared to normoxia controls. Presence of B2BrBC or C66 normalized both contractile and relaxant responses altered by hyperoxia. Both, curcuminoids directly induced dose‐dependent relaxation of preconstricted TSM. Supplementation of hyperoxic animals with B2BrBC or C66, significantly increased catalase activity. Lung TNF‐α was significantly increased in hyperoxia‐exposed animals. Both curcumin analogs attenuated increases in TNF‐α in hyperoxic animals. Conclusion We show that B2BrBC and C66 provide protection against adverse contractility and relaxant effect of hyperoxia on TSM, and whole lung inflammation. Both analogs induced direct relaxation of TSM. Through restoration of catalase activity in hyperoxia, we speculate that analogs are protective against hyperoxia‐induced tracheal hyperreactivity by augmenting H2O2 catabolism. Neonatal hyperoxia induces increased tracheal contractility, attenuates tracheal relaxation, diminishes lung antioxidant capacity, and increases lung inflammation, while monocarbonyl CUR analogs were protective of these adverse effects of hyperoxia. Analogs may be promising new therapies for neonatal hyperoxic airway and lung disease.

The essential oil of Foeniculi fructus, the ripe fruit from the plant Foeniculum vulgare Mill. ssp. vulgare var. dulce Batt. and Trab. (sweet fennel, македонски анасон) was isolated and the main components were identified and quantified using thin-layer chromatography (TLC) and gas chromatography and mass spectrometry (GC-MS). The Aetherloeum Foeniculi had pale yellow color and characteristic pleasant odor and was obtained in 3.2% yield (by weight from the plant fruits). The main components of the oil were: trans-anethole, 1, (70%), p-anisaldehyde, 2, (19%) estragole, 3, (6%) and anisacetone, 4, (2%). The identity of the components was determined by matching the mass spectra to the library spectra. The identity of the main component, trans-anethole, was confirmed directly by isolation using column chromatography and indirectly by potassium permanganate oxidation of the essential oil. The oxidation product from this reaction, pmethoxybenzoic acid, 16, was isolated and characterized. The potential products of autooxidation of trans-anethole (epoxy anethole, anethole glycol and 16) were not detected in the freshly obtained essential oils.

Quantitative Structure Activity Relationships (QSAR or SAR) have helped scientists to establish mathematical relationships between molecular structures and their biological activities. In the present article, SAR studies have been carried out on 89 tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine (TIBO) derivatives using different classifiers, such as support vector machines, artificial neural networks, random forests, and decision trees. The goal is to propose classification models that will be able to classify TIBO compounds into two groups: high and low inhibitors of HIV-1 reverse transcriptase. Each molecular structure was encoded by 10 descriptors. To check the validity of the established models, all of them were subjected to various validation tests: internal validation, Y-randomization, and external validation. The established classification models have been successful. The correct classification rates reached 100% and 90% in the learning and test sets, respectively. Finally, molecular docking analysis was carried out to understand the interactions between reverse transcriptase enzyme and the TIBO compounds studied. Hydrophobic and hydrogen bond interactions led to the identification of active binding sites. The established models could help scientists to predict the inhibition activity of untested compounds or of novel molecules prior to their synthesis. Therefore, they could reduce the trial and error process in the design of human immunodeficiency virus (HIV) inhibitors.

A variety of benzamidomethyl derivatives were prepared in water under alkaline conditions (pH>9) via reaction of (benzamidomethyl)triethylammonium chloride (1) with different inorganic nucleophiles. Reaction of 1 with hydroxylamine did not give the expected mono(benzamidomethyl)-hydroxylamine (3) but rather gave N,N- di(benzamidomethyl)hydroxylamine (2). Reactions of 1 with sodium azide and potassium cyanide gave benzamidomethyl azide (4a) and benzamidomethyl cyanide (4b) respectively. Potassium thiocyanate and sodium iodide reacted with 1, and the anion- exchanged products (benzamidomethyl)triethylammonium isothiocyanate (5a) and (benzamidomethyl)triethylammonium iodide (5b) were thus obtained. Cyanamide and potassium cyanate reacted readily with 1 and both gave the same mixture of di(benzamidomethyl)amine (7) and tri(benzamidomethyl)amine (8). All the reactions occurred smoothly, under mild conditions, to give the products in moderate to high yields.

The title compound was synthesized from 2,7-bis(bromomethyl)naphthalene via two step sequence-partial halogen exchange, followed by hydrolysis. The structure of this product was established by 1H-NMR, 13C-NMR, 19F-NMR, FT-IR spectroscopy and elemental analysis.

A new sulfide, 2-methyl-7-(phenylsulfanylmethyl)naphthalene was synthesized and its MS, IR, 1H NMR, 13C NMR and DEPT-135 data are reported.