The rising demand for sustainable energy storage and carbon mitigation calls for multifunctional materials that integrate high surface area, tailored heteroatom chemistry, and robust electrochemical stability. Herein, we report a continuous three-step synthesis of two novel heterocyclic Schiff base-derived benzoxazine mono-mers-3-(6-methoxybenzo [d]thiazol-2-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (SA-tz Bz) and 3-(6-methox-ybenzo [d]thiazol-2-yl)-3,4-dihydro-2H-naphtho[2,1-e][1,3]oxazine (NA-tz Bz)-through sequential Schiff base formation, reduction, and Mannich condensation. Thermal ring-opening polymerization followed by direct carbonization at 600 and 700 degrees C under an inert atmosphere yielded N, O, S co-doped microporous carbons (C@poly (SA-tz Bz) and C@poly (NA-tz Bz)) without the need for activating agents or wastewater generation. These heteroatom-enriched carbons exhibit disordered amorphous structures with hierarchical porosity, abundant pyridinic/pyrrolic nitrogen species, and oxygen/sulfur functionalities, as confirmed by BET, Raman, XPS, and TEM analyses. Electrochemical studies revealed that C@poly (NA-tz Bz 700) delivers a high specific capacitance of 423 +/- 18 F g-1 at 0.5 A g-1 in a three-electrode system, good cycling stability (98 % retention after 6000 cycles), and superior performance in a symmetric two-electrode device (342 F g-1, 89.50 % retention after 4000 cycles). Moreover, C@poly (NA-tz Bz 700) achieves an exceptional CO2 adsorption capacity of 231.7 cm3 g-1 at 273 K, surpassing many reported heteroatom-doped carbons. This work presents a sustainable strategy for designing heterocyclic benzoxazine-derived microporous carbons that combine efficient energy storage with effective CO2 capture, offering promising prospects for next-generation electrochemical and environmental applications.

Thienopyrimidines represent an important class of nitrogen- and sulfur-containing heterocycles with broad pharmacological relevance. In this work, a new series of thienopyrimidine derivatives was efficiently synthesized through a multistep route involving cyclization, Mannich annulation, Schiff-base condensation, dipyrimidinone ring formation, and acylation, affording structurally diverse fused frameworks. The synthesized compounds were fully characterized using IR, NMR, and mass spectrometry. Their antimicrobial activity was evaluated against representative Gram-positive, Gram-negative strains and fungal strains revealing clear structure-activity relationships. Notably, the Mannich derivative 11 exhibited the highest potency toward Bacillus subtilis, while the fused dipyrimidinone compound 13 demonstrated broadened activity, including inhibition of Escherichia coli. Density functional theory (DFT) calculations provided insight into the electronic structure, intramolecular interactions, HOMO-LUMO distributions, electrostatic potential surfaces, and noncovalent interaction patterns responsible for the observed reactivity and binding behavior. Molecular docking studies against B. subtilis and E. coli DNA gyrase B revealed strong and diverse protein-ligand interactions, consistent with the biological findings, and highlighted compound 13 as the most promising candidate due to its favorable Vina score and extensive hydrogen-bonding and hydrophobic contacts. Collectively, the combined synthetic, biological, and computational analyses underscore the potential of thienopyrimidine scaffolds as valuable agents for developing new antimicrobial agents.

The direct and selective functionalization of abundant light alkanes (C1-C4) is a long-standing challenge in chemical synthesis, and methods to achieve this goal in an enantioselective fashion have remained an unsolved problem due to the high inertness of alkane C-H bonds. Here, we report a photoinduced, palladium-catalyzed, three-component reaction that allows the first enantioselective dialkylation of 1,3-dienes using light alkanes and other unactivated C(sp3)-H feedstocks. The strategy relies on a photogenerated aryl radical to initiate a hydrogen atom transfer (HAT) cascade, activating even the strongest C-H bonds in methane under mild conditions. This versatile methodology provides access to a diverse array of valuable chiral products in high yields and with excellent diastereo- and enantioselectivities. The protocol exhibits a broad scope, encompassing gaseous alkanes, cyclic hydrocarbons, ethers, and carbonyl compounds. Continuous-flow compatibility addresses practical challenges of handling gaseous substrates. Experimental and computational studies confirm that an excited-state palladium-mediated radical pathway is key for achieving stereocontrol and enabling the conversion of the simplest hydrocarbon feedstocks into enantiomerically enriched molecules.

We report the rational design, synthesis, photophysical characterization, and preliminary anticancer assessment of a novel series of hydantoin derivatives functionalized with electron-donating and electron-withdrawing groups at the N-1 and C-5 positions. A versatile and modular synthetic approach afforded rapid access to eleven structurally diverse derivatives exhibiting varied pi-conjugation and donor-acceptor architectures. The photophysical properties of three representative compounds (7, 8, and 13) were systematically investigated in a range of organic solvents using UV-Vis absorption and photoluminescence spectroscopy, as well as in mixed solvent systems to explore their aggregation-induced behaviors. All compounds exhibited two prominent absorption bands corresponding to pi-pi* and intramolecular charge transfer (ICT) transitions, with solventdependent spectral shifts indicative of moderate solvatochromic effects. Photoluminescence studies revealed negative solvatochromism, as increasing solvent polarity resulted in a modest hypsochromic (blue) shift in the emission maxima. In DMSO/water mixtures, fluorescence quenching accompanied by a red shift was observed, suggesting aggregation or non-radiative decay pathways. In vitro cytotoxic evaluation against human breast cancer (MCF-7) cells using MTT assays at concentrations of 0.1, 1, 10, and 100 mu M demonstrated dose-dependent inhibition for compounds 7, 8, and 13, with cell viabilities of 50 %, 41 %, and 28 %, respectively, after 72 hours at 10 mu M. Among them, compound 13 exhibited the highest cytotoxic potency at lower concentrations. Molecular docking simulations with human cyclin-dependent kinase 2 (CDK-2; PDB ID: 1HCK) revealed Vina binding scores of -8.5, -8.6, and -9.9 kcal/mol for compounds 7, 8, and 13, respectively, indicating strong affinity toward the enzyme. These findings are consistent with the biological assay results, highlighting compound 13 as the most promising CDK-2 ligand and a potential lead for further development as an anticancer agent.

This study presents the design, synthesis, and characterization of two novel carbazole-based oxazine monomers, Mono-BenzOx and Mono-NaphthOx, and their corresponding polymers. The monomers, featuring an N-ethyl carbazole moiety, were synthesized through a sequential process of condensation, reduction, and Mannich cyclization, with structures confirmed by FTIR and NMR spectroscopy. Photoluminescence analysis revealed that both monomers exhibit concentration-independent blue emission in solution due to steric hindrance preventing excimer formation. In the solid state, however, a stark difference emerged upon polymerization. While PolyBenzOx showed residual excimer emission, Poly-NaphthOx displayed intense, high-purity blue photoluminescence (CIE: 0.16, 0.05) due to the effective isolation of chromophores within its rigid cross-linked network. Thermogravimetric analysis further established the superiority of the naphthalene-based system compared to the benzoxazine analogue, with Poly-NaphthOx exhibiting a higher decomposition temperature (Td5 = 275 degrees C) and a significantly greater char yield (27 %) than Poly-BenzOx (Td5 = 233 degrees C, char yield: 4 %). The unique combination of efficient solid-state blue emission, exceptional thermal stability, and high char yield puts Poly-NaphthOx as a premier multifunctional material for advanced optoelectronic and high-performance applications.

A series of 1,3,4-oxadiazole-benzimidazole/acetamide derivatives (7a-r) was designed, synthesized, and evaluated for their anticancer activity. NCI-screening results at 10 µM against the 60 human tumor cell line panel revealed a broad-spectrum of antiproliferative effects of the tested compounds. Compounds 7b, 7e, 7f, 7g, 7h, 7k, 7l, and 7r were further tested in a five-dose assay, and they exhibited half-maximal growth inhibitory (GI50) values ranging from 0.90 to 43.50 µM. Focused studies in MDA-MB-231 triple-negative breast cancer (TNBC) cells demonstrated that compounds 7b, 7g, 7h, 7k, and 7l possessed potent antiproliferative activity, with half-maximal inhibitory concentration (IC50) values between 1.92 and 3.69 µM. Mechanistic investigations using cell death pathway inhibitors indicated that compounds 7b, 7k, and 7l did not induce necrosis, apoptosis, or autophagy. Instead, these compounds significantly increased intracellular ferrous iron (Fe2+) and malondialdehyde (MDA) levels and induced lipid peroxidation in MDA-MB-231 cells. In parallel, GPX4 expression was markedly reduced at both the mRNA and protein levels, supporting ferroptosis as the primary mechanism of action. In addition, molecular docking studies and molecular dynamics simulations were performed for derivatives 7b, 7k, and 7l in order to confirm the mechanistic study. Collectively, these findings suggest that the 1,3,4-oxadiazole-benzimidazole/acetamide scaffold represents a promising chemotype for developing ferroptosis-inducing therapeutics targeting TNBC.

A new class of nicotinonitrile derivatives was rationally designed and synthesized to investigate their structural features, photophysical behavior, and anticipated anti-cancer potential. The synthetic strategy enabled the selective preparation of mono- and distyryl nicotinonitrile scaffolds, followed by S-alkylation to afford a diverse set of sulfur-functionalized analogues. The structures of all compounds were unambiguously confirmed using FT-IR, 1H NMR, and 13C NMR spectroscopy. Their optical characteristics were systematically evaluated through UV-Vis absorption and fluorescence measurements, revealing solvatochromic responses and pronounced aggregationinduced emission (AIE) behavior in several derivatives. To elucidate the electronic factors governing these observations, density functional theory (DFT) calculations were performed, providing insight into frontier molecular orbital distributions and electronic transitions that supported the experimental photophysical findings. Furthermore, molecular docking studies were conducted against selected cancer-relevant protein targets, demonstrating favorable binding affinities and interaction profiles that suggest potential anti-cancer activity. Collectively, the integrated experimental and computational investigation highlights these newly synthesized nicotinonitriles as promising scaffolds for future development of photofunctional and biologically active heterocycles.

Schouwia purpurea (Family: Brassicaceae) S. purpurea is a wild medicinal plant traditionally used for treating gastrointestinal, inflammatory, and infectious disorders in arid regions of North Africa. Despite its ethnomedicinal importance, little is known about its systemic safety profile. This study aimed to evaluate the 14-day repeated dose oral toxicity of the aqueous-ethanolic extract of (SPE) S. purpurea in female albino Wistar mice. Thirty mice were randomly assigned into five groups (n = 6): control (distilled water), and extract-treated groups receiving 200, 500, 1000, and 2000 mg/kg of S. purpurea via oral gavage for 14 consecutive days. Animals were observed daily for mortality, behavioral changes, and clinical signs of toxicity. Blood samples were collected for biochemical analysis of liver and kidney function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine. No deaths were recorded in any group. Groups receiving 200 and 500 mg/kg showed no significant changes in biochemical markers. However, a significant dose-dependent elevation in ALT, AST, urea, and creatinine was observed at 1000 and 2000 mg/kg. Additionally, mice in the 2000 mg/kg group exhibited mild lethargy and transient convulsions during the second week, suggesting potential neurotoxic effects, without mortality. These results indicate that the SPE is biochemically and clinically safe at doses up to 500 mg/kg. However, due to the presence of mild histopathological alterations in the liver and kidneys at 500 mg/kg, the dose of 200 mg/kg is established as the no-observed-adverse-effect level (NOAEL), while 500 mg/kg is identified as the lowest-observed-adverse-effect level (LOAEL). Higher doses of SPE may induce dose-dependent hepatic, renal, and neurobehavioral stress.

The increasing resistance of insects to conventional pesticides drives the search for new bioactive heterocycles with novel modes of action. An efficient one-pot protocol was developed for the synthesis of new aminothiazolo[3,2-a]pyrimidine-2-carboxamides as key precursors to pyrimido[4',5':4,5]thiazolo[3,2-a]pyrimidines, offering high yields, short reaction times, and operational simplicity. Density functional theory calculations confirm preferential formation of the thermodynamically stable isomers. Assignment of the chemical structures for the newly synthesized heterocycles was confirmed utilizing elemental and spectral techniques. Furthermore, photoluminescence studies revealed aggregation-induced emission behavior for selected derivatives (2b and 6). Biological evaluation demonstrated notable anti-inflammatory activity, with morpholine-substituted compound 5c showing enhanced efficacy. Insecticidal screening against Aphis gossypii identified compound 5a as the most active candidate, supported by molecular docking indicating strong interaction with the nAChR target. These results highlight compound 5a as a promising lead for insecticidal development. The previous findings were supported by molecular docking studies.

Organocatalysis has been recognized as a part of chemical research for a long time, and it gained significant attention in catalysis in recent decades. Amine catalyst is a substantial type of organocatalysis, and it is successively employed for the activation of carbonyl compounds. This manuscript delves into the exploration of a proline-based organocatalyst for the synthesis of arylidene benzofuranone intermediates, a critical step that facilitates the subsequent construction of aurone-derived azadienes. In this work, we successfully reported the synthesis of arylidene benzofuranone intermediates through Aldol condensation of benzofuranone with different aldehydes enabled by proline-derived organic catalysts. To achieve this strategy, six examples of amine organocatalysts (A1-A6) were evaluated to showcase the optimal catalyst for this transformation. Moreover, the arylidene benzofuranone intermediates were further employed for the synthesis of interesting aurone-derived azadiene substrates through its reaction with TsNH2. Notably, the using of organocatalyst A6 resulted in the delivery of the product with the best yield (94% isolated yield). Under the optimized conditions, different aromatic and heterocyclic containing aldehydes were effectively tolerated to generate the corresponding arylidene benzofuranone intermediates, which further converted to the azadiene products in high to excellent yield. The claimed structures were confirmed by the spectral analysis.

In this study, we report the rational design, synthesis, and computational evaluation of novel thienopyridinebased heterocycles incorporating a thiophene moiety as potential antimicrobial agents. Five thienopyridine derivatives were successfully synthesized and thoroughly characterized using spectroscopic techniques, including nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The in vitro antimicrobial activities of the synthesized compounds were evaluated against a panel of Gram-positive and Gram-negative bacterial strains, as well as fungal pathogens. Most compounds exhibited moderate to strong inhibitory effects, with compounds 10 and 11 showing the highest antibacterial activity, while derivatives 8 and 11 demonstrated the most potent antifungal effects. The introduction of bulky aromatic substituents, such as biphenyl and naphthalene, enhanced both antibacterial and antifungal properties, likely due to increased aromaticity and stronger pi-pi interactions with microbial targets. Additionally, the presence of a cyano (CN) group notably improved antifungal activity. Molecular dynamics simulations indicated that compound 8 formed stable interactions with key residues at the binding site, maintaining complex stability throughout the simulation period. Predictions of drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties revealed a favorable pharmacological profile, supporting its potential as a promising lead compound for the development of potent and low-toxicity antimicrobial agents.

Amyloid beta (Aβ42) aggregation plays a key role in the progression of Alzheimer's disease (AD), contributing to neuronal damage and cognitive impairment. This research examines ovalene, a structurally defined model of graphene quantum dots (GQDs), for its potential to inhibit Aβ42 aggregation. Molecular dynamics simulations indicate that ovalene interferes with Aβ42 protofibril stability in a concentration-dependent manner by disrupting key hydrophobic and aromatic interactions, thus hindering β-sheet formation and fibril growth. Additionally, ovalene prevented Aβ42 dimerization, an early step in amyloid aggregation. Experimental assays, including Thioflavin T fluorescence and circular dichroism, confirmed that ovalene reduces fibril formation while maintaining Aβ42 in its monomeric state. Cytotoxicity studies demonstrated that ovalene counteracts Aβ42-induced toxicity in Neuro-2a cells, with no harmful effects on normal or cancerous cells. In a Drosophila AD model, ovalene significantly lowered amyloid levels, showing the strongest effect at 2 mg/mL. These results support GQD's potential as an anti-amyloid therapy.

The current study investigated the effects of Olea europaea L. cv. Nepal (OEN) leaf extract on obesity-related disorders in rabbits. OEN extract, in dose 100 mg/kg body weight, significantly reduced cholesterol (TC), triglycerides (TAG), and inflammatory markers (MCP-1, VCAM-1, IL-6, IL-1β, TNFα, NF-κB) in both preventative and treatment groups. In addition, heart tissue displayed near-normal collagen fiber distribution. LC-HRESIMS analysis tentatively identified 20 metabolites (1-20) in OEN, including lignans, secoiridoids, and triterpenoids. Network pharmacology analysis suggested 8-hydroxy-p-menth-1-en-7-oic-acid (13), 6,7-dihydroxy-2H-1-benzopyran-2-one 6-O-d-glucopyranoside (5), and 3-hydroxy-12-oleanen-28-oic-acid (20) as key antihyperlipidemic compounds, potentially targeting pathways involved in hyperlipidemia regulation. Furthermore, in silico studies revealed that lignans (compounds 1, 2, and 16) from OEN may bind and inhibit HMG-CoA reductase, a crucial enzyme in cholesterol metabolism. These results indicate the potential of using OEN leaf extract as a therapeutic strategy for managing hyperlipidemia and inflammation associated with obesity. More investigation is necessary to confirm and validate these results and explore the extract's full therapeutic potential.

A new series of benzimidazole-oxadiazole-small molecules were synthesized and confirmed with various spectroscopic techniques. The prepared derivatives exhibited significant inhibitory activity against the proliferation of different cancer cells. The benzimidazoles 10f, 10 h, 10 g, and 10i showed broad anticancer activity with no selectivity in five-dose assays. All prepared compounds displayed potent inhibitory activity against proliferation of a panel of four human cancer cells (HT-29, Panc-1, MCF-7, and A-549) with IC50 values ranging from 24 nM to 80 nM and with significant safety profile against MCF-10 A normal cells. According to the mechanistic study, the most potent compounds (9a, 9b, 10e, 10f, & 10i) displayed remarkable inhibitory effectiveness against EGFR and BRAFV600E and were more potent than reference drugs erlotinib and vemurafenib. Molecular docking study for compounds 9a, 9b, 10e, 10f, and 10i agreed with mechanistic results.

Sarcoptic mange, commonly known as scabies, is a highly contagious skin condition caused by the burrowing mite Sarcoptes scabiei (Astigmata: Sarcoptinae). This parasitic disease significantly impacts livestock and human health, particularly in underserved regions. Current treatments rely on synthetic acaricides like permethrin and ivermectin, which suffer from limitations such as toxicity, resistance development, and environmental contamination. Essential oils from Apiaceae plants represent a promising natural alternative. This study reviewed 122 volatile constituents from Apiaceae plants and conducted comprehensive in silico analyses to identify potential antiparasitic agents. Geraniol emerged as a potent acaricidal candidate due to its strong binding affinity to acetylcholinesterase (AChE) (docking score: - 7.85 kcal/mol). In vitro testing revealed geraniol achieved a 100% mite mortality rate at concentrations as low as 6.25% within 15 min (LT50 = 9.5 min). In vivo studies using scabies-infected rabbits demonstrated that geraniol-treated animals exhibited complete clinical recovery by two weeks post-treatment, with disappearance of crusts, itching, and skin thickening. Histopathological examination showed near-complete skin regeneration with minimal inflammatory infiltrates, in contrast to control groups which exhibited severe lesions and active mite presence. Furthermore, geraniol-treated rabbits displayed new hair growth and improved general condition, with no observed adverse effects. These findings highlight geraniol's potential as a safe, effective, and eco-friendly treatment for scabies, offering a 100% improvement in clinical and histological recovery within two weeks. Further research should focus on optimizing delivery systems and evaluating its efficacy in human clinical trials.

This work focuses on the chemical synthesis of three fluorescent bioactive amides tethered carbazole moiety by coupling 3-amino-9-ethylcarbazole with different aliphatic carboxylic acids including valeric, hexanoic, and heptanoic acids. NMR spectroscopy and HRMS were utilized to confirm the claimed structure of the target compounds indicating good agreement. The antimicrobial activity of fluorescent amides was assessed against different strains of gram negative and gram-negative bacterial as well as fungi demonstrating outstanding activity close or same as the control. Moreover, the molecular design, DFT calculations, and photoluminescence characteristics of these dyes have been investigated. The examined materials solutions emitted a deep-blue emission. Interestingly, with the powders, on the other hand, a single component emitted white light. The creation of aggregated molecules in the solid state improved the emission intensity at long visible wavelengths, resulting in a change in the emission color from the solution to the powder. The studied materials also emitted consistently at high temperatures. Furthermore, the odd-even effect both on the molecular packing and emission characteristics has been proven. As a result, the molecules under investigation provide a unique combination of benefits: a simple molecular structure, deep-blue emitters, white emission from a single material, and an odd-even effect.

The dual targeting of EGFR and HER2 is an established anticancer strategy. A novel series including two distinct scaffolds, A (chalcone-based compounds, 4a-n) and B (pyrazoline-based compounds, 5a-n), was developed and synthesized. The antiproliferative efficacy of 4a-n and 5a-n was examined against a panel of four cancer cell lines. The findings indicated that pyrazoline derivatives 5a-n exhibited more efficacy than chalcone compounds 4a-n. Compounds 4n, 5d, and 5g were identified as the most effective antiproliferative derivatives. These compounds were further investigated as dual EGFR/Her2 inhibitors. Compound 5d inhibited EGFR-TK and HER2 significantly, with IC50 values of 0.126 and 0.061 μM, respectively. Moreover, compound 5d can induce a percentage of pre-G1 apoptosis by 78.53% in cell cycle analysis and cause early apoptosis with necrosis percent of 5.28. Docking and MD simulation illustrated the significant cytotoxic activity of the 5d compound and how it can be a promising scaffold with anticancer activity.

Indroduction COVID-19 is a contagious illness caused by the virus SARS-CoV-2, a major cause of death globally, even with effective vaccinations. Additionally, multidrug resistant bacterial and fungal pathogens are a real threat to many healthcare settings. Sinapic acid (SA), isolated from different plants or marine algae, has been reported to have antioxidant, antibacterial, and antiviral properties. Although there is evidence that SA has anti-SARS-CoV-2 activity, it is poorly absorbed when taken orally due to its intestinal metabolism. The current study aimed to improve SA's activity against SARS-CoV-2, different bacterial and fungal pathogens, bioavailability, and targeting using a nebulized, freeze-dried, transferosomal formulation.Methods A response-surface experimental study using phospholipid, cholesterol, and surfactants was employed to develop transferosomes. Various formulations were prepared and characterized for entrapment efficiency (EE), release, and size to select the optimized formulation. It was then lyophilized into a powder to be evaluated in vivo for its pharmacokinetic properties.Results and discussion SA exhibited antibacterial and antifungal activity, with SA-protransferosomes showing enhanced effectiveness compared to that of pure SA and approaching the efficacy of positive controls. Notably, SA protransferosomes demonstrated activity comparable to that of ciprofloxacin against E. faecalis and S. mutans and were effective against Candida albicans and Aspergillus niger, similar to nystatin. The optimized formula significantly enhanced the SARS-CoV-2 activity (IC50 = 0.016 +/- 0.008 mu g/mL), Cmax by 2.27 times, and AUC (0-infinity) by 5.4 times, as compared to pure SA. As a result, the use of nebulized SA-transferosomes can be regarded as a safe and efficient strategy to counter different infections.

An intermolecular addition of acetophenone derivatives to unactivated alkenes was developed through Pd-(II)/amine cooperative catalysis. This dual catalytic system functions by activating the amide-containing alkene via Pd-(II) coordination while simultaneously enhancing the nucleophilicity of the α-carbon of acetophenones through enamine catalysis, thereby facilitating the C-C bond-forming reaction. Five quinoline-based amide derivatives were designed and synthesized to explore their potential as biologically active agents. The synthesized compounds were structurally characterized using the standard NMR technique and subsequently evaluated for their antimicrobial activity against a panel of pathogenic bacterial and fungal strains. The five derivatives exhibited significant inhibitory effects, with minimum inhibitory concentrations (MICs) comparable to or better than those of reference drugs. To gain insight into the molecular basis of their biological activity, molecular docking studies were performed against relevant microbial target enzymes, revealing favorable binding interactions and high docking scores. Furthermore, molecular dynamics (MD) simulations were carried out to assess the stability and conformational behavior of the most active ligand-protein complexes over time, supporting their potential as stable bioactive candidates. In addition, ADMET in silico predictions indicated good drug-likeness, acceptable pharmacokinetic profiles, and low toxicity risk, reinforcing their potential as promising scaffolds for antimicrobial drug development.