Bisdithiophosphonic acids and their derivatives are strong sulphur- and phosphorus-containing acids with complexing, membranotropic properties and anticipated bioactivity. These acids contain two dithiophosphoryl groups that can associate with basic compounds and metal ions to form organic salts with potential biocidal effects against pathological cells and organisms. In this work, resorcinol and 4,4'-propane-2,2-diyldiphenol were used in the reactions with Lawesson's reagent to synthesize O,O'-(benzene-1,3-diyl)-1,3-bis(4-methoxyphenyl)dithiophosphonic) and O,O'-[propane-2,2-diyl-bis(4,1-phenylene)-bis(4,4'-methoxyphenyl)dithiophosphonic) acids, respectively. The synthesized bisdithiophosphonic acids were converted into disodium and dipotassium salts as well as salts on the basis of (S)-(–)-nicotine, (8R,9S)-quinine, and (8R,9S)-quinidine. Structural characterization of the resulting compounds was carried out using ³¹Р{¹H} and FTIR spectroscopies.

Antibacterial properties of these compounds were assessed in vitro using broth microdilution method. Disodium and dipotassium bisdithiophosphonates were found to be low active against Staphylococcus aureus with minimal inhibitory concentration (MIC) of 1250 μg mL⁻¹. O,O'-(benzene-1,3-diyl)-1,3-bis(4-methoxyphenyl)dithiophosphonic) acid and its salt with (S)-(–)-nicotine showed increased antibacterial effect toward Bacillus cereus with MIC of ca. 78 μg mL⁻¹. Cytotoxicity of the compounds toward human prostate adenocarcinoma (PC-3) cells was additionally studied using resazurin assay upon 24- and 72-hour culture. The synthesized compounds decreased growth of the cancer cells with inhibitory concentrations in micromolar/submillimolar range. The results can be used for further structure evolution of bisdithiophosphonates with antibacterial and cytotoxic activities. This work was funded by the Academy of Sciences of the Republic of Tatarstan in 2024 according to the grant on conducting fundamental and applied research in scientific and educational organizations and enterprises of the real sector of the Republic of Tatarstan.

Hepatitis C virus (HCV) remains a major global health threat, and the non-structural 5B (NS5B) polymerase is a key target for antiviral drug discovery. In this study, a virtual screening strategy was applied to identify novel benzimidazole-based inhibitors of the NS5B polymerase. Molecular docking was first performed to evaluate the binding affinities of a series of benzimidazole derivatives toward the NS5B polymerase active site. Key interactions of the ligand with the receptor active site were identified, displaying common features with those reported for other known inhibitors, thereby reinforcing the validity of the findings. An atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) model was subsequently developed and found to be statistically robust, with high predictive performance for both the training set (R² = 0.95, SD = 0.18, N = 42) and the test set (Q² = 0.79, RMSE = 0.57,N = 11). Guided by these findings, new benzimidazole derivatives were designed as potential NS5B polymerase inhibitors. The most promising compounds were further evaluated for their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties using pkCSM. to assess drug-likeness. This integrated computational approach provides valuable insights into the molecular features governing benzimidazole NS5B binding and identifies promising lead compounds for the development of new hepatitis C virus (HCV) therapeutics.

Cyclooxygenases (COXs) are essential enzymes involved in the biosynthesis of prostanoids, which play key roles in inflammation and various physiological processes. COX-1 is responsible for maintaining normal homeostatic functions, whereas COX-2 is inducible and primarily expressed during inflammatory and pathological conditions. Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibiting COX enzymes; however, their non-selective action often leads to adverse effects, prompting the development of selective COX-2 inhibitors.

Heterocyclic compounds, particularly hydroxyquinolin-2-ones, have attracted significant attention due to their diverse pharmacological activities, including antibacterial, anticancer, and anti-inflammatory properties. In this study, we focused on designing and evaluating in silico of hydroxyquinolin-2-one derivatives as potential therapeutic agents targeting inflammation and infectious diseases.

Molecular docking studies were carried out on the synthesized hydroxyquinolin-2-one derivatives to assess their binding affinity toward the COX enzyme. The results demonstrated promising docking scores for all derivatives, indicating a strong potential for COX inhibition. Compounds with the highest docking scores formed significant interactions with key residues in the COX active site, primarily through hydrogen bonding and other stabilizing interactions. These interactions were facilitated by the presence of carbonyl and hydroxyl groups in the ligand structures, highlighting their crucial role in enhancing binding affinity and stability within the enzyme's active site.

Acetylcholinesterase (AChE) is a critical therapeutic target in the development of small-molecule inhibitors for Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by cognitive decline and cholinergic dysfunction. In this work, 37 tadalafil analogs were studied as potential Acetylcholinesterase (AChE) inhibitors using a combined atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling and molecular docking approach. Molecular docking studies were performed using the Glide program to predict binding affinity within the AChE active site and to validate key interactions responsible for inhibitory activity. The constructed 3D-QSAR model demonstrated excellent statistical robustness and predictive accuracy, showing a high correlation for the training set (R² = 0.975, SD = 0.190, F = 464.7, N = 29) and strong predictive performance for the test set (Q² = 0.809, Pearson(r) = 0.941, RMSE = 0.564 N = 8) using three partial least squares (PLS) factors. Analysis of the 3D-QSAR contour maps revealed critical structural regions where steric and electronic features either enhance or hinder Acetylcholinesterase (AChE) inhibition, providing valuable guidance for rational drug design. Based on these insights, five new candidate molecules were proposed, among which compound X1 exhibited the highest predicted inhibitory activity. These results highlight the power of integrating 3D-QSAR modeling with docking analysis to identify, design, and optimize potent Acetylcholinesterase (AChE) inhibitors, providing a strong foundation for the discovery of novel anti-Alzheimer’s agents.

Due to their broad-spectrum bioactivities and compliance with directed functionalization, pentacyclic triterpenoids (PCTs) are considered a potent molecular platform for novel drug development. Cytotoxic and pro-apoptotic activities of PCTs involving different specific mechanisms are of substantial interest in preferable targeting cancer cells. Replacement of С-3 hydroxyl group of ursolic acid by the nitrogen-containing group was earlier found to promote cytotoxicity of the triterpenoid. In this work, we studied and compared cytotoxicity of pre-synthesized and characterized lupane triterpenoid derivatives containing hydroxyl, amino or carboxymethyl amine groups at C-3 position. According to resazurin assay upon 3-day culture, the modified PCT showed increased inhibitory effect on viability of breast and prostate cancer cells (MCF-7 and PC-3 lines) with half-maximum inhibitory concentrations in the micromolar range. According to flow cytometry analysis with reactive oxygen species (ROS)-specific fluorescent probes, the synthesized compounds exhibited modulating concentration-dependent effects on cytoplasm and mitochondrial ROS levels; the most active derivative caused significant ROS overproduction, which probably underlies its cytotoxic effect. The obtained results contribute to the design of PCT derivatives with potential anticancer properties and encourage further investigation of the compounds. The study was supported by the Subsidy Allocated to Kazan Federal University for the State Assignment in the Sphere of Scientific Activities (project FZSM-2025-0002).

Medicinal plants have long been recognized as valuable sources of natural compounds with significant therapeutic potential. They contain a wide variety of bioactive secondary metabolites, such as alkaloids and phenolic compounds, many of which serve as lead molecules in modern drug discovery. Owing to their structural diversity and broad spectrum of biological activities, these natural products represent an essential resource for developing novel drugs with enhanced efficacy and reduced side effects. In particular, numerous plant-derived compounds have demonstrated promising inhibitory effects against key enzymes, including xanthine oxidase (XO). XO is a crucial enzyme in purine metabolism, catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid.

In this study, three nothoapiol derivatives derived from essential oils were extracted from the medicinal plant Petroselinum sativum by V. Samet et al. These compounds exhibited excellent in vitro antioxidant activity. To further elucidate their mechanism of inhibition and evaluate their potential as XO inhibitors, an in silico molecular docking study was performed. Docking simulations were carried out using Schrödinger Suites 2023, with Glide employing the extra-precision (XP) docking protocol.

The docking results revealed that the nothoapiol derivatives exhibited strong binding affinities, with docking scores comparable to that of quercetin, a well-known standard XO inhibitor. Detailed interaction analysis demonstrated the formation of hydrogen bonds, hydrophobic interactions, and π–π stacking with key active site residues such as Ser876, Lys771, Phe1013, and Glu802, which are critical for XO catalytic activity. These findings suggest that the structural features of the nothoapiol derivatives particularly the presence of hydroxyl and methoxy substituents play a crucial role in enhancing binding stability and specificity.

Introduction

Inflammatory disorders remain a major therapeutic challenge, with current treatments (NSAIDs, corticosteroids) often limited by safety concerns. The inflammatory cascade is largely driven by cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Dual inhibition of COX-2 and 5-LOX has emerged as a promising strategy to achieve effective anti-inflammatory activity with reduced side effects. Acetamide derivatives are known to exhibit diverse medicinal effects.

The present study is based on the synthesis and evaluation of 4-aminoacetanilide scaffolds towards COX-2 and 5-LOX inhibition.

Method

The inhibitory activity of eight synthesized 4-aminoacetanilide derivatives was assessed against COX-2 and LOX using fluorometric and spectrophotometric assays, respectively. IC₅₀ values were determined and compared with the reference drugs Aspirin (COX-2) and Baicalein (LOX). Additionally, molecular docking studies were performed to elucidate the binding interactions of the most active compounds within the catalytic sites of COX-2 and LOX

Results
AI-06 showed notable potency against COX-2 (IC₅₀: 31.2 µM), while AI-02, AI-03, and AI-06 demonstrated strong inhibition of LOX with IC₅₀ values of 14.1, 19.2, and 26.5 µM, respectively. Structure–activity relationship (SAR) analysis indicated that both the position and nature of substituents played a critical role in determining inhibitory activity. Molecular docking further revealed key binding interactions responsible for the observed potency.

Conclusion
The findings suggest that AI-02, AI-03, AI-06, and AI-08 hold promise as dual COX-2/5-LOX inhibitors and could be further optimized as potential anti-inflammatory agents.

Modification of the known structures of photosensitizers (PS) in purpose to improve their properties is an important direction in the development of new agents for photodynamic therapy (PDT). Among the approaches, the incorporation of different metals in the structure of the PS molecule can be distinguished. In this research, we investigated the photophysichemic and photobiological properties of tetrakis(3-methyl-1-phenyl-pyrazole-4-yl)-tetracyanoporphyrazine (PzPyr) and its metal complexes containing iron and palladium cations in the center of the macrocycle.

Two absorption bands were observed for the studied compounds: in the short-wavelength (Soret band) and long-wavelength (Q-band) regions, and fluorescence in the red region of the spectrum with peak at 620-650 nm. The compounds demonstrated a significant increase in fluorescence intensity in a more viscous medium, which suggests that they belong to the class of fluorescent molecular rotors.

We did not observe any visible differences in the accumulation dynamics for PzPyr and FePzPyr – the maximum accumulation occurred 1 hour after the start of incubation, indicating a high rate of uptake by A431 cells. At the same time, PdPzPyr showed a longer accumulation time of more than 5 hours.

Evaluation of the cytotoxicity of the compounds showed that they exhibit a low level of dark toxicity, while maintaining visible photodynamic activity A431 cells. The addition of a metal cation resulted in a significant increase in the photodynamic index compared to the free base. Inhibitory analysis demonstrated that FePzPyr and PdPzPyr are able to induce cell death along the immunogenic pathway.

Analysis of the compounds has shown that they can be used as potential drugs, and the addition of a metal atom opens up broad prospects for improving the effectiveness of PDT, for example, by activating immunogenic cell death pathways.

FSWR-2023-0032

Over the past two decades, gut dysbiosis has gained significant attention due to its multifaceted involvement in diverse health disorders. Gut barrier dysfunction increases intestinal permeability, which allows gut-derived toxicants into the systemic circulation and contributes to adverse health outcomes. The proteins, including zona occludens 1 (ZO-1), occludin, and claudin 4, maintain the integrity through forming a tight junction complex and restricting the entrance of noxious substances through the intestinal epithelial apical layer. It had been reported that the reduction in the relative expression of mucosal junctional proteins can trigger a broad spectrum of disorders, including inflammatory bowel diseases, renal impairment, neurocognitive dysfunctions, autoimmune disorders, colorectal cancer, and others. Preclinical studies demonstrate the role of puerarin in restoring the intestinal barrier function through increasing the levels of tight junction proteins and exerting anti-inflammatory and antioxidant effects. Furthermore, previous scientific evidence suggested the deteriorating effects of higher concentrations of adenine on the intestinal barrier functions. This study aims to elucidate the molecular docking of puerarin and adenine against the ZO-1, occludin, and claudin 4. Puerarin shows a lesser binding energy against ZO-1 (−7.187 kcal/mol) and claudin 4 (−9.193 kcal/mol), whereas no significant results were obtained in the case of occludin. They exhibit stronger hydrophobic interaction and hydrogen bonding to the amino acid residues present at the active site of the ZO-1 and claudin 4. In contrast, adenine displayed fewer interactions, likely due to its inhibitory effects at the active site pockets of ZO-1, occludin, and claudin 4. These findings suggest that puerarin may have therapeutic potential in modulating tight junctional proteins. However, further in vitro and in vivo studies are required to determine the preventive effects against gut dysbiosis-associated health complications and intestinal disorders.

The development of phosphorus-containing compounds with specific biocidal action and low toxicity profile is a promising direction in medicinal chemistry. Chiral properties of such compounds may contribute to their selective interactions with biological targets. In this study, racemic alcohols were reacted with 2,4-diaryl-1,3,2,4-dithiophosphetane-2,4-disulfides to yield chiral dithiophosphonic acids. O-2-Ethylhexyl-4-methoxyphenyldithiophosphonic acid 1 was prepared by the reaction of Lawesson’s reagent with 2-ethylhexanol in benzene upon moderate heating. The reaction of diethyl malate with Lawesson’s reagent was carried out at ambient temperature to form O-[1,2-di(ethoxycarbonyl)ethyl-1] 4-methoxyphenyldithiophosphonic acid 2. The compound 1 was reacted with ammonia, (S)-(–)-α-methylbenzylamine, (R)-(+)-α-methylbenzylamine, α-methylbenzylamine, pyridine, and pyridoxine to give corresponding ammonium, chiral methylbenzylammonium, pyridinium, and pyridoxinium dithiophosphonates. Hexadecylammonium O-[1,2-di(ethoxycarbonyl)ethyl-1] 4-methoxyphenyldithiophosphonate was obtained by the reaction of the compound 2 with hexadecylamine.

The synthesized salts of dithiophosphonic acids were evaluated for their in vitro bacteriostatic/bactericidal properties against Staphylococcus aureus, Bacillus subtilis, and Bacillus cereus using broth microdilution method. According to minimal inhibitory concentrations (MIC) revealed, the compounds showed good antibacterial activity with MIC in the range from 7 to 116 μg mL⁻¹. Hexadecylammonium salt of dithiophosphonic acid on the basis of diethyl malate was the most effective against the bacterial growth. The study was supported by the Subsidy Allocated to Kazan Federal University for the State Assignment in the Sphere of Scientific Activities (project FZSM-2025-0002).