Derivatives of 1,3,5-oxadiazine are of considerable interest for pharmacy, medicine and agriculture due to their wide spectrum of biological activity. These heterocyclic compounds exhibit antimicrobial, anti-inflammatory, antitumor and insecticidal properties, which makes them promising structures for the creation of new medicinal and agrochemical preparations. This work presents a step-by-step synthesis of a new derivative of 1,3,5-oxadiazine. In the first step, by reacting N-(1-amino-2,2,2-trichloroethyl)acetamide with 2-bromobenzoyl isothiocyanate, a previously undescribed thiourea, N-((1-acetamido-2,2,2-trichloroethyl)carbamothioyl)-2-bromobenzamide, was obtained. In the next step, this compound was treated with dicyclohexylcarbodiimide (DCC), resulting in cyclization and the formation of a new derivative of 1,3,5-oxadiazine - N-(1-(((2E,4E)-6-(2-bromophenyl)-3-cyclohexyl-2-(cyclohexylimino)-2,3-dihydro-4H-1,3,5-oxadiazin-4-ylidene)amino)-2,2,2-trichloroethyl)acetamide. The reaction was carried out in acetonitrile at reflux for one hour. Presumably, in the first step of the transformation, under the action of DCC, the elimination of a hydrogen sulfide molecule occurs with the formation of an intermediate carbodiimide derivative - N-(((1-acetamido-2,2,2-trichloroethyl)imino)methylene)-2-bromobenzamide. This intermediate then undergoes a [4+2] cycloaddition reaction with another DCC molecule to form the desired 1,3,5-oxadiazine product in 82% yield. Its structure was confirmed by NMR spectroscopy (¹H and ¹³C).

The strategy and tactics of organic synthesis of 6-(5-mercapto-4R-4H-1,2,4-triazol-3-yl)pyrimidine-2,4(1H,3H)-dione derivatives offer a versatile platform for the development of new heterocyclic compounds. These molecules combine the biologically relevant 1,2,4-triazole ring, known for its antimicrobial and antioxidant properties, with a pyrimidine-2,4-dione core structurally related to vitamin B13 (orotic acid), essential in nucleic acid metabolism. This dual structure opens a wide spectrum of synthetic possibilities, particularly in heterocyclization reactions.

The synthetic strategy generally starts with the formation of the triazole ring through cyclocondensation of thiosemicarbazides with appropriate carbonyl precursors, followed by functionalization of the thiol group via S-alkylation or S-arylation. The pyrimidine-2,4-dione fragment allows further diversification via nucleophilic substitutions and condensation reactions, broadening the chemical diversity and potential biological activity of these compounds.

Key aspects of the synthesis include the careful choice of reaction conditions to control regioselectivity and product yields. The interplay between the triazole and pyrimidine moieties also enables annulation strategies, expanding the scope of possible structures. The vitamin B13 motif not only imparts biological relevance but also acts as a bioisostere of nucleobases, supporting the rational design of new drug candidates.

This work highlights the importance of integrating heterocyclization strategies with functional group transformations to access a broad range of 6-(5-mercapto-4R-4H-1,2,4-triazol-3-yl)pyrimidine-2,4(1H,3H)-dione derivatives with promising biological potential.

Benzoxazoles are compounds of considerable interest in the field of organic synthesis. The advancement of materials chemistry has led to the development of new materials with diverse applications, including semiconductors, electroluminescent materials, and functional photoluminescent materials. These compounds exhibit an electronic push-pull phenomenon due to the delocalization of the π system, a characteristic highly desirable for the development of materials with optoelectronic properties, such as organic light-emitting diodes (OLEDs). This study explores the role of the cyanide ion (CN-) in the reaction kinetics between aminophenols (1a-c) and benzaldehydes (2a-c), which serve as imino-precursors (3a-i) in the cyclization process leading to the formation of benzoxazoles (4a-i). The multicomponent synthesis conditions were as follows: one equivalent of Ar-CHO, one equivalent of aminophenol, 10% PhB(OH)₂ dissolved in a minimal amount of methanol, and one equivalent of KCN dissolved in 0.5 mL of distilled water. The total reaction mixture volume was 3 mL, and it was maintained at room temperature and atmospheric pressure for three hours. Real-time monitoring of the reaction was conducted using online NMR with a continuous flow cell on a Magritek Spinsolve 80 MHz proton NMR spectrometer, in conjunction with ATR-FTIR analysis via a Perkin Elmer Spectrum 100 IR spectrometer. Changes in the concentration of the imines (3a-i) indicated that the cyanide ion is involved in the reaction mechanism, following second-order kinetics. This observation suggests that the cyanide ion acts as a reactant in the cyclization process rather than merely as a catalyst.

Isocyanide-based Multicomponent Reactions (IMCRs) are domino processes in which three or more components react to form a complex molecule containing all or most of the atoms of starting materials. They have several advantages over multistep syntheses and other domino processes, e.g. convergence, modularity, operational simplicity, safety, high overall yields and lower costs. IMCRs are recognized as one of the best synthetic tools in organic chemistry; furthermore, they fulfill most of Green Chemistry Principles and are considered as the closest to an ideal synthesis in the green chemistry field.

Ugi four-component reaction (Ugi-4CR) is the most studied IMCR, and typically involves an isocyanide, a carbonyl compound, an amine and a carboxylic acid. It has proven to be an efficient and rapid tool for the synthesis of bis-amides, a peptidomimetic scaffold which is relevant for medicinal chemistry and organic synthesis. In the latter, they can be used as synthetic platform for synthesizing heterocycles, bis-heterocycles and even polyheterocycles via IMCR-post transformation strategies.

Recently, Ugi-4CR has been successfully applied for the synthesis of triterpenoid analogs, however this field is still underexplored, and several downsides can be observed, such as long reaction times and moderate yields.

Herein, we present the synthesis of a small series of bis-amide triterpenoid analogs employing masticadienonic acid, a triterpenoid with carboxylic acid function isolated from aerial parts of Pistacia mexicana.

The Raman spectrum of adenine and the surface‐enhanced Raman spectrum (SERS) upon adsorption of adenine on an Ag₈ cluster in aqueous solution were calculated using the density functional theory method with the PBE0 hybrid functional and the Def2‐TZVP basis set, together with the integral equation formalism polarizable continuum model for the solvent (IEF‐PCM). TD‐DFT calculations were performed to determine the excitation wavelengths of adenine and the Ag₈•A complex, thereby selecting excitation wavelengths compatible with available experimental Raman spectroscopy instruments. In addition, excitation wavelengths with the maximum oscillator strength were chosen to propose characteristic spectra for experimental studies. The calculated Raman activities were converted into Raman scattering intensities, and the enhancement factor was determined. The results show that an excitation wavelength of 325 nm gives the strongest and most distinct SERS signal, 532 nm provides stable signals suitable for commercial instruments, while 442 nm significantly reduces several characteristic vibrational bands. The study also constructed Raman and SERS spectra corresponding to the excitation wavelength with the maximum oscillator strength. The findings indicate that the Ag₈ cluster greatly enhances the Raman signal of adenine. This study provides a basis for selecting excitation wavelengths and characteristic vibrational modes to identify adenine, supporting the development of label‐free biosensors based on silver clusters.

1,5-disubstituted tetrazoles (1,5-Ds-T) are heterocyclic bioisosteres of the cis-amide bond and are widely employed in medicinal chemistry to enhance the pharmacokinetic and pharmacodynamic properties of peptidomimetics. Their incorporation can improve potency, selectivity, and metabolic stability while reducing toxicity. Beyond their biomedical applications, 1,5-Ds-T have been used as ligands, chelating agents, metal-organic framework precursors (MOFs), and bioimaging probes.

On the other hand, chromones are privileged scaffolds found in a wide range of natural products and are well recognized for their broad spectrum of biological activities, including anticancer, antimicrobial, antidiabetic, anti-inflammatory and antioxidant properties.

Isocyanide-based multicomponent reactions (IMCR) are efficient tools to synthesize nitrogen heterocycles, such as 1,5-Ds-T. Among them, the Ugi-azide four-component reaction (UA-4CR) stands out for its versatility and mild reaction conditions for the one-pot synthesis of 1,5-Ds-T. This UA-4CR involves an aldehyde or ketone, an amine, an isocyanide, and an azide source, commonly trimethylsilyl azide (TMSN₃), which generates hydrazoic acid in situ.

Herein, we report a one-pot process via the UA-4CR for the synthesis of 1,5-Ds-T incorporating a chromone moiety, under mild conditions, affording moderate overall yields (46-59%). This strategy approach provides a valuable platform for generating novel tetrazole–chromone analogs with potential application in medicinal chemistry and materials science.

Diabetes is a chronic metabolic disorder characterized by persistently high blood glucose levels due to insulin malfunction, defective insulin secretion, or both. Chromen-4-one, known to have diverse biological activity, is a core structure found in many natural products, particularly in the flavonoid and isoflavonoid families. The study aims to explore the potential of Chrome-4-one derivatives as a potential antidiabetic agent through the α-glucosidase inhibition mechanism. The compounds were retrieved from the PubChem database, optimized, and prepared using ChemDraw 12.0, Spartan14, and UCSF Chimera. The post-docking analysis was done using BIOVIA Discovery Studio. Theoretical oral bioavailability and toxicity predictions were performed using ADMETlab3.0. Molecular docking of the compounds against the α-glucosidase enzyme (PDB ID: 3A4A) was carried out using AutoDock Vina. According to Lipinski’s rule of five (5), all the ligands passed the oral bioavailability and are druggable. The binding score of all the ligands was better than the native ligand (-5.7 Kcal/mol) but slightly lower than that of Acarbose (-9.0 Kcal/mol), except for L7 (Myricetin), which equals the standard drug. The ligands revealed good interaction with the enzyme’s active site residues. The most notable interactions were hydrogen bonding, van der Waals, pi-anion, pi-cation, pi-pi T-shape, pi-sigma, and carbon-hydrogen bond. The ligands interacted with the key catalytic residues; ASP352, GLU277, GLU411, TRY158, and ARG442, responsible for α-glucosidase inhibition. The result of the study suggests that the chromen-4-one derivatives have the potential to be utilized as a lead molecule for orally available α-glucosidase inhibitors.

The chemistry of thieno[2,3-b]pyridine derivatives still remains a rapidly developing area of research, which has repeatedly become the subject of detailed consideration in a number of papers and reviews and dissertations. In recent years, significant progress has been made in this area of heterocyclic chemistry, which is reflected in a significant number of new publications concerning methods for the preparation, modification, and especially issues of biological activity of thieno[2,3-b]pyridine derivatives. It is important to note that thieno[2,3-b]pyridine derivatives are used in various fields , which confirms their importance and prospects for further research. In this regard, further study of these compounds plays an important role in the development of scientific knowledge and practical application in the modern world.

6-Aminopyridine-3,5-dicarbonitriles and 3,6-diamino-5-cyanothieno[2,3-b]pyridines are well known as compounds with a broad spectrum of bioactivity. In particular, such thienopyridines are known as inhibitors of scrapie prion infection replication and accumulation, as well as selective inhibitors of malaria plasmodia kinase-3 with a pronounced antimalarial effect.

To expand the range of such compounds, we studied the reaction of 3,6-diaminothieno[2,3-b]pyridine-5-carbonitriles with chloroacetyl chloride. The analysis of the Fukui indices showed that in these compounds the amino group at the C(3) atom is the most reactive. In fact, the reaction with ClCH2C(O)Cl leads to the predicted product. Other reactions of thienopyridines as well as data on the biological activity of the products are discussed.

Luteolin is a naturally occurring flavonoid with growing interest for its senolytic properties. However, its poor water solubility and low bioavailability limit clinical application. This study aimed to develop and compare two types of nanocarriers, liposomes and polymeric nanoparticles, for the efficient delivery of luteolin in senolytic therapies. Liposomes with luteolin were prepared using the lipid film hydration method, followed by sonication and extrusion. Polymeric nanoparticles were developed via the nanoprecipitation method using pullulan acetate, a hydrophobic derivative obtained by chemical functionalization of pullulan. Pullulan was biosynthesized over 72 hours using the microorganism Aureobasidium pullulans ICCF 36 (from CMII – INCDCF-ICCF). The formulation used a polymer-to-luteolin ratio of 10:1 (g/g) and Pluronic F127 as a stabilizer. Nanoprecipitation was carried out under controlled conditions: stirring at 700 rpm and dropwise addition at 0.5 mL/min. Luteolin was successfully encapsulated in both delivery systems. Liposomes showed an encapsulation efficiency of 85.07 ± 0.09% and nanoscale diameter. Polymeric nanoparticles demonstrated an encapsulation efficiency of 74.87 ± 0.05% ,nanometric size and a formulation yield of 73.29 ± 0.09%. Both liposomal and polymeric nanoparticle systems effectively encapsulated luteolin, with high efficiency and yield. The formulations present promising potential for use in senolytic therapies, targeting age-related cellular dysfunction. Further studies will assess their release kinetics, biological activity, and senolytic effects in vitro and in vivo.

Acknowledgements: This work was suported through the “Nucleu” Program, Contract no. 1N/2023, Project code PN 23-28 carried out with the support of MCID, project no. PN 23-28 03 01.

N-(Hydroxymethyl)thioamides are readily available compounds that are widely used in the synthesis of nitrogen- and sulfur–containing heterocycles such as 1,3-thiazines, 1,2,4-dithiazoles, 1,3,5-oxathiazines, 1,3,5-thiadiazines, thiazolidines, and others. In addition to its use in fine organic synthesis, N-(hydroxymethyl)thioamides are also used for other purposes. For example, some representatives of this class act as bidentate ligands to create selective sorbents for heavy metal ions such as Cu(II), Cd(II) and Hg(II). These compounds are intermediates in the synthesis of a number of biologically active substances. At the same time, a limited number of methods for obtaining compounds of this type are presented in the literature, and the variability of structures is not high enough. Thus, N-(hydroxyalkyl)thioamides belong to a promising group of compounds, and the development of methods for the synthesis of such compounds can be considered an important problem. Cyanothioacetamide readily reacts with aromatic aldehydes in an aqueous alcohol medium in the presence of triethylamine as a catalyst to form arylmethylenzyanothioacetamides (3-aryl-2-cyanothioacrylamides). The latter reacted with HCHO to give N-(hydroxymethyl) derivatives. In this paper, a method for preparation of new derivatives of N-(hydroxyalkyl) thioacrylamides was proposed. The synthetic details and spectral data are discussed. The biological effects as herbicide 2,4-D safeners is also discussed.