This research focuses on synthesizing novel tetrahydroquinoline-1,2,3-triazole hybrids as potential agents for neurodegenerative diseases, particularly Alzheimer's disease (AD). The series of structurally distinct hybrid compounds synthesized in this study are previously unreported in the literature. The synthetic strategy involved a diastereoselective imino Diels-Alder reaction (Povarov reaction) to construct the tetrahydroquinoline (THQ) core, where various catalysts, including phthalic acid, lewis acids, KSF (montmorillonite), and ceric ammonium nitrate (CAN), were screened. Phthalic acid was selected as the most efficient catalyst for this crucial step. Following this, efficient click chemistry was employed to introduce the triazole moiety, adhering to green chemistry principles throughout the process. The chemical structure of the synthetized compounds was assigned using analysis of Nuclear Magnetic Resonance (NMR), Mass Spectrometry (MS) and Infrared (IR) spectroscopy. Furthermore, in silico analyses performed with Swiss ADME and OSIRIS Property Explorer indicated that most compounds exhibited excellent drug-like characteristics and favorable pharmacokinetic profiles. The synthesized compounds were evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman's methodology. The inhibitory activity is presented as values for each enzyme and compared to galantamine as a reference standard. These findings offer promising directions for the development of new therapeutic agents for AD based on organic synthesis.

Introduction

At the moment, the chemistry of heterocyclic compounds is actively developing. Particularly attractive are spirocyclic heterocompounds, which are of great interest from a synthetic point of view in chemical science due to their predominance in a wide range of pharmacologically important compounds. In particular, sulfur-containing hybrid heterocycles are the structural units of many biologically active natural compounds.

Experimental details

We have developed the conditions and studied the interaction of (E)-3-[(2-oxo-5-arylfuran-3(2H)-ylidene)methyl]-4H-chromen-4-ones with 1,4-dithiane-2,5-diol at room temperature using acetonitrile as a solvent. The final products of the transformation are 3-(3-aryl-9-hydroxy-1-oxo-2-oxa-7-thiaspiro[4.4]non-3-en-6-yl)-4H-chromen-4-ones. The composition and structure of sulfur-containing hybrid heterocycles were established on the basis of complex data from elemental analysis, IR, ¹H, ¹³C NMR, HSQC, HMBC spectroscopy.

Results and Discussion

The reaction under study is a cascade reaction and occurs in two stages. Initially, there is a thio-Michael addition of 2-mercaptoacetaldehyde (generated in situ from 1,4-dithiane-2,5-diol) to (E)-3-[(2-oxo-5-arylfuran-3(2H)-ylidene)methyl]-4H-chromen-4-ones. Then, intramolecular condensation occurs, which leads to the construction of a five-membered tetrahydrothiophene framework and the formation of the final hybrid compounds - 3-(3-aryl-9-hydroxy-1-oxo-2-oxa-7-thiaspiro[4.4]non-3-en-6-yl)-4H-chromen-4-ones.

In recent years, the consumption of fish products has led to a worrying trend where approximately two-thirds of the total amount of fish is discarded as waste. At the same time, scientific interest in exploring natural collagen sources has increased. This study explores the potential of valorizing sardine scales (Sardina pilchardus), a by-product of the canning industry, through the extraction of collagen for potential use in cosmetic formulations and food supplements.

Collagen from sardine scales was obtained through acid and enzymatic extraction. The extracts were characterized by UV-Vis, FTIR, SDS-PAGE, powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The collagen was hydrolyzed with papain to small peptides. Subsequently, the biological activities of acid-soluble collagen and the collagen peptides in terms of antioxidant and antimicrobial activity were evaluated. Furthermore, the capacity of collagen peptides to permeate the intestinal barrier, simulated with caco-2 cells, was evaluated. Purified collagen extracts were obtained, with the enzymatic extraction method yielding three times higher than the acid method. The SDS-PAGE analysis confirmed the extraction of type I collagen as well as its hydrolysis into small fragments (25-12 kDa). While no antimicrobial activity was observed, collagen peptides exhibited three times more antioxidant capacity than non-hydrolyzed collagen. Meanwhile, in 6 hours, about 6.37 % of collagen peptides could permeate the intestinal barrier.

This work represents a continuous effort to advance our understanding and valorization of marine co-products, focusing on collagen extraction for the development of food supplements, thus contributing to the sustainable evolution of the circular blue economy.

Several derivatives of piperazin have been recognized for a broad spectrum of pharmacological activities , so this study involved the synthesis of a series of novel triazole derivatives based on piperazine (2-(4-(prop-2-yn-1-yl)piperazin-1-yl)pyrimidine) and some organic azide via click chemistry in good yield . The reaction was monitored using thin-layer chromatography (TLC). All newly synthesized piperazine derivatives (1–5) were characterized by Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (¹H-NMR), and (¹³C-NMR). Some physical properties were also measured, including color, retention factor (Rf) , m.p .

The biological activity of the compounds was tested against two microbial strains: one Gram-positive and and one Gram-negative (Escherichia coli), bacterium (Staphylococcus aureus) and one fungal strain (Candida albicans). The antibacterial activity of the compounds (1–5) was determined, it was shown that the derivatives had an exceptionally high degree of effectiveness at a certain concentration. Additionally, the antioxidant activity was evaluated using the (Phosphomolybdate) method, revealing that the derivatives exhibited significant antioxidant activity compared to ascorbic acid at a certain concentration, with compound (3) showing the highest antioxidant potential.

Molecular docking studies of the synthesized piperazine derivatives were also conducted against the 2X08 protein. The docking results showed varying binding affinities among the compounds, with compound 3 displaying the highest inhibitory effect, correlating with the biological assay results.

Medium-chain aliphatic compounds bearing oxygen-containing functional groups—such as alcohols, ketones, or carboxylic acids—have attracted increasing attention due to their potential as bioactive agents in pest management. These compounds have demonstrated diverse biocidal properties, including insecticidal, antimicrobial, fungicidal, and nematicidal activities. In this study, the nematicidal potency of three structurally related C9 aliphatic ketones—2-nonanone, 3-nonanone, and 5-nonanone—was evaluated against Bursaphelenchus xylophilus, the pinewood nematode (PWN). These isomeric ketones differ in the position of the carbonyl group, providing a useful model for examining structure–activity relationships (SAR) among positional isomers.

The direct-contact bioassays performed at 1 mg/mL revealed that 2-nonanone exhibited the highest nematicidal activity, causing 92.3±1.2% mortality on the PWN, followed by 3-nonanone at 80.1±0.8%, while 5-nonanone showed significantly lower activity at 17.1±0.5%. The results suggest a strong dependency of bioactivity on the position of the carbonyl group along the carbon chain. The increasing efficacy from 5- to 2-nonanone suggests that proximity of the carbonyl group to the terminal end may enhance activity, for example by enhancing membrane interaction or disrupting nematode metabolic processes. These findings underscore the importance of molecule structure analysis in designing effective nematicidal agents and support further investigation into terminally positioned oxygenated medium-carbon chain aliphatic compounds as potential leads. This work highlights that subtle structural differences within homologous series can significantly influence bioactivity and provides a foundation for developing targeted, biodegradable nematicides derived from simple aliphatic frameworks.

In this research, a sandwich-type polyoxometalate (Cu) was conveniently prepared and characterized by different methods. Characterization of the obtained nanomaterial was performed using Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS) and elemental mapping as well as X-ray diffraction analysis (XRD) methods. This nanomaterial can effectively facilitate the synthesis of 4H-pyran derivatives, as a heterogeneous nanocatalyst, in a one-pot reaction through multi-component reactions (MCRs) strategy. This heteropolyonion-based nanocatalyst possessed suit-able acidic and basic active sites, enabling it to serve as a multifunctional catalyst. The Cu6W18O70 nanocatalyst demonstrated high product yields and short reaction times. also, the low need for catalyst and solvent and on the other hands, are use of solvent non-toxic are other benefits of this catalyst in reactions. Furthermore, the heterogeneous catalyst exhibited remarkable reusability, maintaining its catalytic activity for at least five cycles without significant loss of its efficiency. In this study, the nanocatalyst will serve as a heterogeneous and effective catalyst for the multicomponent synthesis of 4H-pyrans. The reaction is done through present of dimedone, malonitrile, and an aldehyde as reactants. The characterization of this newly synthesized heterogeneous compound will be conducted using various tech-niques. the catalytic performance of this nanocomposite will be evaluated in the one-pot multicomponent synthesis of 4H-pyrans.

Introduction. According to research data, 1,3-oxazines are pharmacologically active substances, as well as the substrates for the synthesis of heterocyclic and acyclic compounds. However, bis(1,3-oxazin-6-one) derivatives are little studied class of compounds, which makes their research a promising direction for the development of modern synthetic chemistry and pharmacy. The aim of this work is to obtain bis(4-hydroxy-6H-1,3-oxazin-6-ones), study their alcoholysis reaction, prove the structure of the obtained products and evaluate their pharmacological potential in silico.

Methods. The reflux of isophthalic acid diamide with a twofold excess of substituted malonyl chloride in 1,2-dichloroethane for 15 hours led to the production of bis(4-hydroxy-6H-1,3-oxazin-6-ones) (1, 2). As a result of their reflux with absolute ethanol for 5 hours acyclic esters of malonamic acids (3, 4) formed. The structure of the obtained compounds was proved by ¹H and ¹³C NMR spectroscopy. The prediction of biological activity was carried out using the GUSAR and PASS online web-resources.

Results. The yields of compounds 1-4 were 90%, 90%, 93%, 89%, respectively, depending on the nature of the substituent at position C₅ of the oxazine cycle. According to the in silico assessment of biological activity, bis(1,3-oxazine-6-ones) exhibited high probability of antitumor activity, while ethyl esters of malonamic acids showed promising anxiolytic, antieczematous, fibrinolytic activities.

Conclusions. New bridging 1,3-oxazin-6-ones were synthesized. The reaction of their cleavage by absolute ethanol to malonamic acid esters was studied. The potential biological activity was predicted in silico.

Diphenol, occurring in various pharmaceutical and natural molecules, has been concerned as efficient substrates or precursors for derivation of aromatic moiety [1]. Due to the broad synthetic application and highly sensitive reactivities, the selectivity-controlling of protection and derivatization of hydroxyl groups is an innegligible challenge to achieve the desired chemical conversion [2]. In addition, alkylation of hydroxyl group in phenol is not only the protection methods [3,4], the alkyloxy groups are key scaffolds in a great deal of functional molecules [5]. However, the common alkylation reagents, such as halides, alkyl sulfates and sulfonates have been confined for their environmental toxicity, potential danger to health [7,8].

Utilizing alcohols as green alkylating reagents, sulfonyl chloride-promoted directed alkylation of monophenols were achieved. Based on such results, a one-pot synergistic alkylation-sulfonylation reaction of diphenol was developed in the presence of the weak base, potassium carbonate, and sulfonyl chlorides using alcohols as alkylating reagents (Scheme 1). Based on this method, the hydroxyls in resveratrol could be functionalized definitely to produce compound 3 in good yield (Figure 1).

Scheme 1. One-pot synergistic alkylation-sulfonylation of diphenol

Figure 1. Synergistic alkylation-sulfonylation of resveratrol

Therefore, a novel method was provided for efficiently synergistic alkylation-sulfonylation of hydroxyl groups in diphenols, which had the potential application in the unsymmetrical derivatization of multiple hydroxyls in polyphenols.

Phosphonamidates are a class of organophosphorus compounds that can exhibit peculiar flame retardant properties thanks to the P-N synergism in gas and condensed phase. Herein we report the straightforward synthesis of 6-(1,3-dimethylureido)dibenzo[c,e][1,2]oxaphosphinine 6-oxide (DOPO-N^urea) from the commercially available H-phosphinate 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO). The final product was obtained in high yield in a single step by reacting under mild conditions DOPO and 1,3-dimethylurea in the presence of a mild oxidant and triethylamine as base. DOPO-N^urea was characterized by multinuclear NMR, ATR-IR, absorption and emission spectroscopies. The couplings with the ³¹P nucleus resulted particularly useful for the unambiguous assignment of the NMR resonances. The structure and selected spectroscopic features of DOPO-N^urea were simulated by means of density functional theory calculations. Given the presence of a P–N bond between the phosphoryl group and one of the urea nitrogen atoms, of potential interest in the field of sustainable flame retardants, the thermal properties of the new phosporamidate were investigated through differential scanning calorimetry and thermogravimetry. The compound melts without decomposition around 140 °C. At about 150 °C an initial weight loss was observed, compatible with the decomposition of the urea moiety. The flame retardant properties of DOPO-N^urea in bio-based polymers are under current investigation.

Despite decades, the synthesis and application of new chiral Amino Acids (AA) and peptides derived from them remain research topics of major importance. Compared with conventional alfa-AA, the introduction of gamma-AA into the corresponding peptides can lead to peptidomimetics with different secondary structures and improved hydrolytic stability towards peptidases, thus enabling better biological properties/activities. Gamma^2,2-AA are useful building blocks for the development of original chiral small molecules and heterocycles, enabling exploration of 3D chemical space in search of selectivity in biological properties, and prevent racemization at the alfa position of the carbonyl functional group.

The catalytic synthesis of versatile chiral heterocycles: en route to gamma-AA derivatives is a project that aims to develop versatile chiral heterocycles as building blocks for access to gamma-AA derivatives, using Meldrum acid chemistry and new developments in Phase Transfer Catalysis (PTC) approaches. Thanks to the Meldrum acid chemistry we succeeded in developing a robust, versatile and efficient synthetic route for the synthesis of pyridazinone derivatives, 6-membered aza-heterocycles considered as masked gamma-AA, as platforms for PT-catalyzed asymmetric Michael additions to obtain pyridazinone derivatives di-substituted on the alfa-carbonyl position. Using this process, we achieved good yields and enantiomeric excesses up to 86%. Finally, by performing synthetic transformations, we obtained the corresponding gamma-AA derivatives.