Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. 30–50% of its cases are caused by the BCR-ABL1 fusion gene as a driver oncogene. In this research work, a study of the cytotoxic properties of phthalimido-1,3- thiazole derivatives against the BCR-ABL protein PDB ID: 4WA9 was carried out using a combination of different computational chemistry methods, including a molecular docking/dynamics study and ADM-T evaluation. Six top hits were identified based on their free energy scores E score (Kcaol/mol), namely 4WA9-L21, 4WA9-L20, 4WA9-L22, 4WA9-L19, 4WA9-L18 , and 4WA9-L18, which demonstrated better binding affinity (from -8.36 to −9.29 kcal/mol). Furthermore, Molecular dynamics simulation studies support the molecular docking results and validate the stability of the studied complexes under physiological conditions. These results confirm that the hits selected are verifiable inhibitors of the BCR-ABL protein, implying a good correlation between in silico and in vitro studies. Moreover, in silico ADME-TOX studies were used to predict the pharmacokinetic, pharmacodynamics, and toxicological properties of the studied hits. These findings support the future role of phthalimido-1,3-thiazole derivatives against the Acute lymphoblastic leukemia disease and may help to find a new therapeutic combination of drugs to treat relapsed acute lymphoblastic leukemia and improve overall survival.

Background: Isoxazole derivatives are a class of heterocyclic compounds with significant pharmacological relevance, known for their antimicrobial, anticancer, and anti-inflammatory activities. These molecules are pivotal in medicinal chemistry due to their structural versatility and potential as drug candidates. This study explores a novel synthetic pathway to produce (3-(4-bromophenyl)-isoxazol-5-yl)-methyl acetate, aiming to expand the library of bioactive isoxazole derivatives for future pharmacological evaluations.
Methods: A three-step synthetic approach was employed to obtain the target compound. First, 2,4-dimethylbenzaldehyde was reacted with hydroxylamine hydrochloride in the presence of pyridine to form the corresponding oxime. This intermediate underwent a cyclization reaction with propargyl alcohol and sodium hypochlorite in dichloromethane, yielding the core isoxazole structure. Finally, esterification of the isoxazole derivative was performed using acetic acid and concentrated sulfuric acid to produce the desired compound. Structural characterization and purity analysis were conducted using FT-IR, ¹H NMR, and ¹³C NMR spectroscopy.
Results: The synthesis successfully yielded (3-(4-bromophenyl)-isoxazol-5-yl)-methyl acetate as a dark brown liquid with a 62% yield. FT-IR analysis revealed characteristic absorption bands at 1631 cm⁻¹ and 1716 cm⁻¹. The ¹H and ¹³C NMR spectra provided detailed confirmation of the compound’s structure, demonstrating the success of the synthetic route. Additional derivatives with fluorine and methoxy substituents were synthesized with yields of 60–72%.
Conclusions: This study outlines an efficient and reproducible synthesis of novel isoxazole derivatives with potential pharmaceutical applications. Future studies will focus on their biological activities and therapeutic potential.

The innovative PABSA-Pr-PMO catalyst represents a significant advancement in nanomaterial design for sustainable catalysis. By combining periodic mesoporous organosilica (PMO) with p-aminobenzenesulfonic acid (PABSA) via a co-condensation process followed by sequential integration, the material achieves a hierarchical structure with exceptional thermal stability, a high surface area, and uniform mesopores. These features create abundant, accessible active sites while ensuring robustness for repeated use. The precise engineering of Brønsted acidic sites from PABSA enhances proton-transfer efficiency, critical for activating C–H acids in multicomponent reactions. In the Traube–Schwarz reaction, PABSA-Pr-PMO catalyzes the synthesis of imidazopyrimidine derivatives—compounds with pharmaceutical relevance, including anticancer and antimicrobial properties—by efficiently coupling 2-aminobenzoimidazole, C–H acids, and aromatic aldehydes under mild conditions. The catalyst’s performance excels with ultralow loading , driving reactions to completion within 5 –15 minutes versus hours with conventional acids. Yields reach 90–99%, emphasizing precision in product formation.Its recyclability, maintaining >90% activity after five cycles, underscores economic and environmental benefits, aligning with green chemistry principles. The absence of toxic solvents or excessive energy input further reduces the process footprint. This protocol not only streamlines synthesis but also demonstrates scalable potential for industrial applications, offering a reusable, efficient alternative to homogeneous catalysts. By merging advanced nanomaterial design with sustainable reaction engineering, PABSA-Pr-PMO exemplifies a transformative approach to green chemical manufacturing, bridging molecular innovation with practical scalability.

Acute Myeloid Leukemia represent only 1.1% of all cancer diseases in the United States, on the contrary though, has one of the highest estimated mortality rates for the year 2025, where near 50% of affected patient will face unfavourable outcome [1]. While Feline McDonough Sarcoma-like tyrosine kinase 3 was identified as a primary deregulated target, Quizartinib had been developed to specifically inhibit the inactive conformation of the kinase, nevertheless is facing tolerance due to point mutation in the Kinase Domain and Internal Tandem Duplication mutations, accountable for the modified length of the juxta-membrane domain [2]. In this study we used an in-silico approach to build a novel series with different heterocyclic-based compounds, more likely to form stronger acceptor-donor interaction than Quizartinib with Cys694 in the hinge, while a novelty covalent bond in the region of the pocket where the point mutation occurs has been investigated. Pyrazine-based compounds covalently bound via cyano-moiety, showed an unreported pose in the binding pocket, enhanced by a stabilizing interaction with Asp829 in the activation-loop. Hence theoretically, the series seems to be unaffected by F691L mutation. Molecular Dynamics simulation will be crucial to monitor the activation-loop flexibility and the impact of the novel pose in the binding pocket, while stability of the complexes and binding-unbinding processes will be studied. Synthesis and the in-vitro testing will serve for data collecting and biologically validation of the series.

Introduction. Bridged 1,3-diazine systems attract considerable interest in organic and medicinal chemistry. At the same time, Schiff bases are of particular interest to researchers as effective complexing agents for various ions. There is no doubt that bridged 1,3-diazine systems potentially possess a sufficiently broad spectrum of biological activity. Therefore, the synthesis and study of novel azomethine systems based on pyrimidines represents a highly promising research direction, as it opens possibilities for obtaining new biologically active compounds.
Material and methods. The aim of our work was the synthesis of novel bridged systems based on 4,6-dihydroxypyrimidine-5-carbaldehydes. A series of bisazomethines was obtained through the nucleophilic addition reaction of m- and p-phenylenediamines to the carbonyl group of
4,6-dihydroxypyrimidine-5-carbaldehydes. During the synthesis of target compounds, methanol and water were used as solvents, with practical yields being comparable under these conditions. The structures of the target compounds were confirmed by ¹H and ¹³C NMR spectroscopy.
Results. According to in silico screening data using web resources PASS-online, CLC-pred, Antivir-pred and GUSAR-online, the synthesized bisazomethines demonstrate a broad spectrum of biological activity (antibacterial, antifungal and antiviral), and are classified as Class 4 toxicity according to the OECD project classifier.
Conclusion. Thus, a series of novel bridged bisazomethines based on 5-formyl derivatives of pyrimidine-4,6-diols was obtained, exhibiting both a high safety profile and promising types of biological activity. The newly synthesized bisazomethines are also of great interest as unique ligands for the preparation of transition metal complexes, which potentially have high prospects for pharmaceutical applications.

The fundamental principle of photolithography is that the crosslinking or degradation reaction of the photoresist causes a significant change in solubility. Traditional positive photoresists currently rely on the photoinduced decomposition of diazonaphthoquinone sulfonate (DNQ) or the deprotection of tert-butoxycarbonyl (Boc) groups to release carboxyl groups. However, there are several issues associated with these approaches: 1. DNQ is used in large quantities (25%) and is not heat-resistant; 2. Acid diffusion leads to increased line-edge roughness. To address these issues, we have developed a photoinduced alkyne domino 1,1-dicarboxylation reaction and applied this method to the working mechanism of positive photosensitive polyimide photoresists. This method can directly prepare water-soluble carboxyl-functionalized molecules and polymers from hydrophobic alkyne precursors. In this work, we synthesized five different types of photosensitive polyimides, all of which exhibited significant changes in solubility before and after exposure. Notably, this photochemical reaction is carried out under alkaline conditions, which can avoid acid corrosion that may affect the quality of the lithographic patterns.Moreover, under thermal treatment conditions, the residual alkyne groups can undergo crosslinking reactions, making the photoresist film more stable and providing better mechanical properties. This demonstrates the potential application value of our method in semiconductor manufacturing lithography technology. This research is of great significance.

Black raspberries exhibit polyphenolic radical scavenging activity. It was carried out through the assays on galvinoxyl radical absorption and emission spectra. Black raspberries are rich in polyphenols, such as anthocyanins and ellagic acid, which contribute to their potent antioxidant activity. These polyphenols effectively neutralize free radicals such as the galvinoxyl radical, as demonstrated by studies that have measured their neutralization capacity. Galvinoxyl radical absorption and emission spectra were used to evaluate the efficacy of these antioxidants in neutralizing the radical via quenching and/or scavenging. These spectra and also chemiluminescence assay provide information about the interaction between the antioxidant extracts and the reactive oxygen substances (ROS). The position and number of hydroxyl groups in polyphenols can influence their scavenging ability, with ortho-hydroxy positions often being more effective. Polyphenols in black raspberries can donate electrons or hydrogen atoms to free radicals, neutralizing them and preventing oxidative damage. Polyphenols, particularly flavonoids, can effectively scavenge free radicals due to their structural features, such as the presence of a 3',4'-dihydroxy group (catechol structure). Black raspberries extract showed an efficient scavenging activity in darkness of galvanoxyl radical in ethanolic solutions. The reactivity of this extract toward galvanoxyl (a model phenoxyl radical) in ethanol solution was also investigated.

Abietane diterpenoids exhibit a wide range of bioactivities, including antimicrobial, anticancer, anti-inflammatory, and antiviral effects. The abietane diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy), extracted from Plectranthus grandidentatus, has exhibited significant cytotoxic effects against a sereral cancer cell line. To improve its anticancer efficacy, several semi-synthetic derivatives of Roy were developed and subjected to extensive in silico evaluation.

This computational assessment involved the prediction of pharmacokinetic parameters, including absorption, distribution, metabolism, excretion, and toxicity (ADMET), to determine drug-likeness and safety profiles. The potential anticancer activity of each compound was estimated using PASS (Prediction of Activity Spectra for Substances), while density functional theory (DFT) was employed to analyze molecular stability and electronic properties. Furthermore, molecular docking and molecular dynamics (MD) simulations were conducted to assess the interaction strength and stability of the derivatives with cancer-associated protein targets.

ADMET modeling suggested that the compounds possessed favorable pharmacokinetic characteristics and acceptable toxicity levels. DFT-based quantum chemical calculations revealed alterations in HOMO–LUMO energy gaps (ranging from 3.39 to 3.79 eV) and provided insights into global reactivity descriptors. PASS analysis predicted strong anticancer potential, with probability scores between 0.819 and 0.879.

Docking studies indicated strong binding affinities toward key oncogenic targets, including cyclin-dependent kinases (CDKs), BCL-2, caspases, receptor tyrosine kinases, and p53, with MD simulations confirming the stability of the ligand–protein complexes.

Altogether, the results reinforce the promise of Roy and its derivatives as potent anticancer agents and support further experimental validation.

Type 2 diabetes mellitus (T2DM) poses a significant public health challenge, affecting millions worldwide. Developing novel drugs to address the underlying causes of the disease is thus a research priority. However, the quest for novel potent alpha-glucosidase inhibitors (AGIs) persists to enhance treatment outcomes and minimize adverse effects. This study elucidates the inhibitory potential of a series of 1-deazapurines against the enzyme alpha-glucosidase. Molecular docking was employed to determine the affinity of these compounds for the active site of alpha-glucosidase using the Molecular Operating Environment (MOE) program. The stability of the top three ligands with the enzyme receptor was validated through dynamic simulation analysis. Promising pharmacokinetic characteristics and oral bioavailability of these compounds were revealed through ADMET and Drug-likeness predictions. Molecular docking results show that Methyl 6-(2-hydroxybenzoyl)-3-(2-phenylethyl)imidazo[4,5-b]pyridine-5-carboxylate, 5-(furan-2-yl)-3-(4-methoxybenzyl)-2-phenyl-7-(trifluoromethyl)imidazo[4,5-b]pyridine, and 3-[2-phenylethyl]-5-thiophen-2-yl-7-(trifluoromethyl)imidazo[4,5-b]pyridine possess the lowest respective energy scores of -6.1247 kcal/mol, -5.7030 kcal/mol, and -5.5403 kcal/mol. Furthermore, these compounds exhibit compliance with Lipinsky, Ghose, Muegge, Egan and Veber rules, indicating good gastrointestinal absorption and oral bioavailability. These results clearly demonstrate that these ligands could serve as potential precursors for developing drugs against Type 2 diabetes mellitus. thereby offering promising avenues for addressing the therapeutic challenges associated with diabetes and related metabolic disorders.

Parasitic diseases are some of the most lethal and pervasive infections globally, causing millions of cases of morbidity and mortality annually.Plasmodium falciparum is the predominant vector-borne pathogen, resulting in 0.5 million fatalities annually.Malaria, caused by Plasmodium falciparum, continues to be a significant worldwide health issue, requiring the development of novel treatment medicines to address increasing medication resistance. This study undertakes a focused in silico screening of phytochemicals derived from Centella asiatica against dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), represented by PDB ID: 3BWK. This work investigated molecular modeling to clarify the probable mechanism of its anti-malarial activity through the suppression of falciparum proteins. Campesterol exhibits a maximal binding affinity (docking score: −8.6 Kcal/mol) for FP-2 from Plasmodium falciparum, as determined by our molecular docking investigation of 30 bioactive compounds from Centella asiatica. However, Ursolic acid and rutin also showed potential activity with significant docking scores (−8.5 and 8.4 Kcal/mol). Campesterol, recognized as a possible inhibitor of falciparum, offers a viable pathway for the treatment of malaria, necessitating additional investigation into its therapeutic use. This research provides significant insights into the molecular interactions between phytochemicals, facilitating innovative and successful strategies for malaria treatment. Our research indicates that polyphenols derived from Centella asiatica exhibit significant pharmacological potential against several biological targets.