Bushra Shakoor

This study aimed to evaluate the behavioral and biochemical effects of synthesized flavonols (1-10) as potential nootropic, antidepressant, and antistress agents. Behavioral assessments were conducted using animal models to evaluate memory impairment, depression, and stress responses. The cognitive effects of flavonols were analyzed using spontaneous alternation, discrimination ratio, and step-down latency tests, while antidepressant activity was determined through forced swim (FST) and tail suspension (TST) tests. All synthesized flavonols (1-10) significantly improved spontaneous alternation and discrimination ratios and increased step-down latency compared to the amnesic group. These compounds also markedly reduced immobility time in both FST and TST, indicating strong antidepressant-like effects. Biochemical analyses supported these behavioral outcomes by revealing enhanced cholinergic activity and reduced oxidative stress. Molecular docking studies against acetylcholinesterase (PDB IDs: 4EY7 & 6O4W) showed strong binding affinities, particularly for flavonol derivatives, through key hydrogen-bonding and π–π interactions. Flavonols (1-10) demonstrated significant behavioral, biochemical, and computational evidence of neuroprotection, suggesting their therapeutic potential in managing cognitive dysfunction, depression, and stress-related disorders.

Coumarin-based scaffolds have emerged as versatile structural platforms in modern medicinal chemistry due to their broad pharmacological spectrum and ease of functional modification. This review provides a comprehensive and up-to-date analysis of coumarin hybrid molecules reported between 2022 and 2026, highlighting recent advances in biological evaluation and its mechanistic understanding. Particular emphasis is placed on structurally diverse hybrids such as urea, hydroxamate, triazole-isatin, thiadiazole, and other multifunctional coumarin derivatives developed as therapeutic candidates across oncology, neurodegenerative disorders, and antimicrobial research. A systematic structure-activity relationship (SAR) discussion reveals that biological performance is strongly influenced by substitution patterns on the coumarin ring, linker length and flexibility, and the presence of pharmacophoric fragments enabling metal coordination, hydrogen bonding, and π-interactions. Hence, this review highlights the therapeutic significance of coumarin hybrids and their potential as promising lead scaffolds for future drug development.

AIMS: ) as potential nootropic, antidepressant, and antistress agents. MATERIALS AND METHODS: Behavioral assessments were conducted using animal models to evaluate memory impairment, depression, and stress responses. The cognitive effects of flavonols were analyzed using spontaneous alternation, discrimination ratio, and step-down latency tests, while antidepressant activity was determined through forced swim (FST) and tail suspension (TST) tests. RESULTS: ) significantly improved spontaneous alternation and discrimination ratios and increased step-down latency compared to the amnesic group. These compounds also markedly reduced immobility time in both FST and TST, indicating strong antidepressant-like effects. Biochemical analyses supported these behavioral outcomes by revealing enhanced cholinergic activity and reduced oxidative stress. Molecular docking studies against acetylcholinesterase (PDB IDs: 4EY7 & 6O4W) showed strong binding affinities, particularly for flavonol derivatives, through key hydrogen-bonding and π-π interactions. CONCLUSIONS: ) demonstrated significant behavioral, biochemical, and computational evidence of neuroprotection, suggesting their therapeutic potential in managing cognitive dysfunction, depression, and stress-related disorders.

antidiabetic assessment in streptozotocin-induced diabetic rats. Treatment with the selected derivatives improved glycemic control and favorably modulated diabetes-associated physiological and biochemical alterations, including body weight changes, lipid profile disturbances, and elevated hepatic biomarkers. Molecular docking studies were performed to investigate the binding modes of the synthesized compounds within the active sites of α-glucosidase and aldose reductase, while molecular dynamics simulations were conducted to assess the stability of the protein-ligand complexes over time. Furthermore, density functional theory (DFT) calculations were employed to explore the electronic properties and reactivity patterns of the synthesized derivatives. In addition, ADMET analysis was performed to assess their pharmacokinetic and drug-likeness characteristics. These findings support 4-aminochalcones as promising dual α-glucosidase and aldose reductase inhibitors.

This study aimed to evaluate the behavioral and biochemical effects of synthesized flavonols (1-10) as potential nootropic, antidepressant, and antistress agents. Behavioral assessments were conducted using animal models to evaluate memory impairment, depression, and stress responses. The cognitive effects of flavonols were analyzed using spontaneous alternation, discrimination ratio, and step-down latency tests, while antidepressant activity was determined through forced swim (FST) and tail suspension (TST) tests. All synthesized flavonols (1-10) significantly improved spontaneous alternation and discrimination ratios and increased step-down latency compared to the amnesic group. These compounds also markedly reduced immobility time in both FST and TST, indicating strong antidepressant-like effects. Biochemical analyses supported these behavioral outcomes by revealing enhanced cholinergic activity and reduced oxidative stress. Molecular docking studies against acetylcholinesterase (PDB IDs: 4EY7 & 6O4W) showed strong binding affinities, particularly for flavonol derivatives, through key hydrogen-bonding and π–π interactions. Flavonols (1-10) demonstrated significant behavioral, biochemical, and computational evidence of neuroprotection, suggesting their therapeutic potential in managing cognitive dysfunction, depression, and stress-related disorders.

This study aimed to evaluate the behavioral and biochemical effects of synthesized flavonols (<b>1-10</b>) as potential nootropic, antidepressant, and antistress agents. Behavioral assessments were conducted using animal models to evaluate memory impairment, depression, and stress responses. The cognitive effects of flavonols were analyzed using spontaneous alternation, discrimination ratio, and step-down latency tests, while antidepressant activity was determined through forced swim (FST) and tail suspension (TST) tests. All synthesized flavonols (<b>1-10</b>) significantly improved spontaneous alternation and discrimination ratios and increased step-down latency compared to the amnesic group. These compounds also markedly reduced immobility time in both FST and TST, indicating strong antidepressant-like effects. Biochemical analyses supported these behavioral outcomes by revealing enhanced cholinergic activity and reduced oxidative stress. Molecular docking studies against acetylcholinesterase (PDB IDs: 4EY7 &amp; 6O4W) showed strong binding affinities, particularly for flavonol derivatives, through key hydrogen-bonding and π–π interactions. Flavonols (<b>1-10</b>) demonstrated significant behavioral, biochemical, and computational evidence of neuroprotection, suggesting their therapeutic potential in managing cognitive dysfunction, depression, and stress-related disorders.

This study aimed to evaluate the behavioral and biochemical effects of synthesized flavonols (<b>1-10</b>) as potential nootropic, antidepressant, and antistress agents. Behavioral assessments were conducted using animal models to evaluate memory impairment, depression, and stress responses. The cognitive effects of flavonols were analyzed using spontaneous alternation, discrimination ratio, and step-down latency tests, while antidepressant activity was determined through forced swim (FST) and tail suspension (TST) tests. All synthesized flavonols (<b>1-10</b>) significantly improved spontaneous alternation and discrimination ratios and increased step-down latency compared to the amnesic group. These compounds also markedly reduced immobility time in both FST and TST, indicating strong antidepressant-like effects. Biochemical analyses supported these behavioral outcomes by revealing enhanced cholinergic activity and reduced oxidative stress. Molecular docking studies against acetylcholinesterase (PDB IDs: 4EY7 &amp; 6O4W) showed strong binding affinities, particularly for flavonol derivatives, through key hydrogen-bonding and π–π interactions. Flavonols (<b>1-10</b>) demonstrated significant behavioral, biochemical, and computational evidence of neuroprotection, suggesting their therapeutic potential in managing cognitive dysfunction, depression, and stress-related disorders.

Objective: The present investigation sought to conceptualize and fabricate a novel series of azo-oxazine-tetrazole hybrids (C1-C3) and to assess their prospective utility as antibacterial agents by integrating them into pH-responsive nanocomposites derived from TEMPO-oxidized Cellulose Nanocrystals (CNCs). The primary aim was to establish a controlled drug delivery system that demonstrates efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA). Methods: The synthesis of azo-oxazine-tetrazole compounds was conducted through a series of multi-step chemical reactions, followed by their conjugation with TEMPO-oxidized CNCs. Structural validation was performed using Fourier-transform infrared (FT-IR) spectroscopy, and surface morphology was characterized by Scanning Electron Microscopy (SEM). Antibacterial activity was assessed employing the disc diffusion method, whereas molecular docking studies against the bacterial 6LXH protein elucidated binding affinities. Additionally, drug loading, release kinetics under variable pH conditions (5.5 and 7.4), and ADME (absorption, distribution, metabolism, excretion) characteristics were examined utilizing SwissADME computational tools. results: FT-IR confirmed successful formation of target hybrids and their CNC conjugates. SEM imaging showed uniform CNC distribution with fibrils averaging 15 ± 3 nm. Drug-loading efficiencies ranged from 79% to 86%. Among the synthesized compounds, C2 exhibited the highest antibacterial activity, with a 28 mm inhibition zone at 300 µg/mL against MRSA. Molecular docking showed strong binding interactions (MolDock score: –141.428) between C2 and bacterial protein target. Release studies indicated significant pH-dependent release, with 92% of the drug released at pH 5.5 compared to 68% at pH 7.4. SwissADME analysis confirmed C2 and C3 follow Lipinski’s Rule of Five and exhibit high gastrointestinal absorption with minimal blood-brain barrier penetration. Results: FT-IR spectroscopy corroborated the successful synthesis of the hybrids and their conjugation to CNCs. SEM analysis illustrated uniform CNC fibrils with an average diameter measuring 15 ± 3 nm. The drug-loading efficiencies ranged from 79% to 86%. Among the evaluated compounds, C2 demonstrated the most pronounced antibacterial activity against MRSA, with an inhibition zone of 28 mm at 300 μg/mL. Molecular docking analyses indicated a significant binding affinity for C2, reflected in a MolDock score of -141.428. The drug release exhibited pH sensitivity, achieving 92% release at pH 5.5 and 68% at pH 7.4. Compounds C2 and C3 displayed favorable drug-likeness and low gastrointestinal absorption, coupled with minimal penetration across the blood-brain barrier. Discussion: This investigation demonstrates the successful formulation of pH-sensitive antibacterial nanocomposites with enhanced drug-delivery properties. The superior performance of C2 can be ascribed to its robust molecular interactions with bacterial proteins and its effective release in acidic environments, which are typically encountered at infection sites. Such findings underscore the hybrid's potential as a targeted therapeutic approach for combating drug-resistant infections. conclusion: This study presents a novel nano-antimicrobial platform that combines synthetic chemistry, nanotechnology, and molecular modeling to combat drug-resistant infections. The developed CNC-conjugated azo-oxazine-triazole hybrids, particularly C2, demonstrate potent antibacterial activity, controlled release behavior, and drug-likeness, making them strong candidates for further therapeutic development. Conclusion: The synthesized azo-oxazine-tetrazole-CNC nanocomposites, particularly C2, exhibit promising antibacterial efficacy, pH-responsive drug release profiles, and advantageous pharmacokinetic properties. These results substantiate their potential for application in the design of nextgeneration nanocarrier systems to address resistant bacterial infections.

In this study, the synthesis of polyphenol oxidase (PPO)-functionalized aluminum oxide (Al 2 O[Formula: see text] nanoconjugates (NCs) using Pleurotus ostreatus extracts has been carried out, which also assesses their antioxidant, phenolic degradation, and molecular interaction capabilities through the combined experimental and computational methods. PPO extraction optimization showed optimal enzyme activity (maximum of 130 U/mL) to be at 3% biomass concentration, 25 mL of extractant, 120 min of incubation time, and [Formula: see text]C. The structural characterization revealed that PPO was successfully synthesized onto Al 2 O 3 NCs, and the presence of crystalline Al 2 O 3 NCs phases, enzyme-to-nanoparticle interactions via Fourier transform infrared (FTIR) spectroscopy, morphology (spherical to global) via scanning electron microscopy (SEM), and particle sizes (nanoscale) via dynamic light scattering (DLS) process were found. PPO-coated Al 2 O 3 NCs performed better antioxidant capacity, with the highest diphenyl-1-picrylhydrazyl (DPPH) radical scavenging rate of 66.64 ± 3.33%, which was better than both the free Al 2 O 3 NCs and the natural antioxidant ascorbic acid in the same solution. The use of immobilized Al 2 O 3 NCs in assays of phenolic wastewater treatment showed better degradation efficiency, which yielded a 1.69-fold increase in enzyme activity under fluorescent light and a 1.86-fold increase in enzyme activity under photocatalytic conditions, suggesting an effective catalytic turnover and adsorption of the pollutant. Molecular docking showed that the phenolics in mushrooms had a high binding affinity with PPO-related targets, and rutin (−123.16 kcal/mol), catechin (−118.90 kcal/mol), and apigenin (−118.23 kcal/mol) had significantly high binding affinities compared with ascorbic acid (−85.22 kcal/mol). The adsorption, distribution, metabolism, excretion (ADME), and toxicity studies confirmed positive pharmacokinetics and low predicted toxicity in lead compounds, and density functional theory (DFT) calculations revealed reduced highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gaps and increased electronic reactivity in apigenin as compared to ascorbic acid. Taken together, these results ensure the use of PPO-coated Al 2 O 3 NCs as an efficient, sustainable, and multi-functional platform of antioxidant applications and phenolic wastewater treatment.

A series of pyrimidine derivatives ( 1–12 ) was synthesized and investigated as multifunctional bioactive molecules based on their promising molecular docking profiles against cholinesterase targets, which provided the rationale for subsequent biological evaluation. The synthesized compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition, anticonvulsant activity, anticancer potential, and computational characteristics. Among the tested compounds, compound 4 exhibited the highest cholinesterase inhibitory activity with IC 50 values of 0.70 ± 0.03 µM (AChE) and 2.90 ± 0.12 µM (BChE), while compounds 1 , 2 , 9 , and 11 also showed potent dual enzyme inhibition (AChE IC 50 = 0.95–1.60 µM; BChE IC 50 = 3.60–4.20 µM). In vivo anticonvulsant studies demonstrated that compound 4 produced the greatest seizure protection, achieving 83% protection in the maximal electroshock seizure (MES) model and 85% protection in the pentylenetetrazole (PTZ) model at 20 mg/kg, whereas compounds 1 , 2 , 9 , and 11 also exhibited pronounced dose-dependent anticonvulsant effects. In cytotoxicity studies, compounds 2 and 11 displayed selective antiproliferative activity against SH-SY5Y neuroblastoma cells with IC 50 values of 45.6 and 46.3 µM, respectively, while exhibiting comparatively low toxicity toward normal neuronal cells. Molecular docking demonstrated favorable binding of the lead compounds within the active sites of AChE and BChE through multiple hydrogen-bonding and hydrophobic interactions, supporting the observed experimental activities. Hence, the combined computational and experimental findings identify compounds 2 , 4 , and 11 as promising lead pyrimidine derivatives for further optimization as multifunctional agents targeting cholinesterase-associated neurological disorders with additional selective anticancer potential.

A multidisciplinary experimental and computational investigation of 2,5-di(pyridin-4-yl)-1,3,4-oxadiazole (compound 4) is reported. The compound was synthesized and characterized using FTIR, NMR, ESI-MS, and single-crystal X-ray diffraction, confirming its molecular structure and crystallographic features. To explore its possible pharmacological relevance, SwissTargetPrediction, molecular docking, molecular dynamics simulations, ADME/toxicity prediction, and DFT calculations were performed. SwissTargetPrediction suggested possible interactions with several protein classes, while molecular docking indicated favorable predicted binding poses of compound 4 within selected protein targets, particularly MurA and JAK2. Molecular dynamics simulations over 50 ns supported the preliminary stability of the corresponding protein-ligand complexes under the applied simulation conditions. ADME predictions suggested acceptable rule-based drug-likeness parameters, including predicted gastrointestinal absorption and blood-brain barrier permeability. However, in silico toxicity assessment also indicated potential safety alerts, including hepatotoxicity, neurotoxicity, and carcinogenicity risks, which require experimental verification. DFT calculations at the B3LYP/6-311G level, together with NBO, MEP, and Hirshfeld-related analyses, provided additional insight into the electronic distribution, charge-transfer behavior, and intermolecular interaction features of compound 4. Overall, the combined experimental and computational results identify compound 4 as a structurally confirmed oxadiazole scaffold with computationally suggested interactions toward selected biologically relevant targets. Nevertheless, its predicted biological properties should be considered preliminary and require further in vitro and in vivo validation.

In the present study, a series of structurally diverse vanillin sulfonate derivatives ( 1–9 ) were synthesized and evaluated as potential α-glucosidase inhibitors through integrated in vitro, in vivo, and in silico approaches. The target compounds were obtained via sulfonation and subsequent functional modification of the vanillin scaffold and were fully characterized using standard spectroscopic techniques. Enzyme inhibition assays demonstrated that several derivatives exhibited strong α-glucosidase inhibitory activity, with inhibitory constants significantly lower than that of the reference drug, indicating enhanced potency. The synthesized compounds showed notable α-glucosidase inhibitory activity, with compounds 8 (IC 50 = 7.8 ± 2.2 µM), 6 (IC 50 = 10.2 ± 1.1 µM), and 5 (IC 50 = 13.4 ± 1.9 µM) exhibiting stronger activity than acarbose (IC 50 = 28.3 ± 1.2 µM), indicating their potential as promising antidiabetic candidates. To the best of our knowledge, this study represents the first in vivo evaluation of vanillin sulfonate derivatives for antihyperglycemic activity. Selected lead compounds were further evaluated in an oral carbohydrate tolerance model, where they produced a significant reduction in postprandial blood glucose levels without observable acute toxicity. Molecular docking and dynamic simulation studies supported the experimental findings by revealing stable binding interactions within the catalytic pocket of α-glucosidase, including hydrogen bonding and π–π stacking with key active-site residues. Density functional theory (DFT) calculations further clarified the electronic properties, frontier molecular orbitals, and reactivity descriptors of the most active derivatives, correlating electronic parameters with inhibitory performance. Collectively, these results identify vanillin sulfonates as promising lead structures for the development of new α-glucosidase inhibitors and support their further optimization as potential antidiabetic agents.

Nutritional and hydration support provide the foundation for wound healing. When the body is injured, the nutritional and fluid demands increase to support tissue restoration, healthy immune response, and good recovery. Proteins are critical nutrients in wound recovery to increase blood vessels, produce collagen, and repair tissue. Eating protein at every meal and as a snack provides more protein to meet these increased demands, but certain amino acids, like arginine, leucine, and glutamine, are useful to help collagen production, repair muscle, and aid in common pathway for managing oxidative stress. Calories also need to increase during wound healing to better address the demands of metabolic processes. Carbohydrates are essential for immediate energy; fats, especially omega-3 fatty acids (higher in fish and fish oil), provide structural components to the cell membrane and mediate inflammatory repair.

Aims Tyrosinase and pancreatic lipase are key enzymes involved in melanin biosynthesis and lipid metabolism, respectively. Their inhibition offers therapeutic potential in treating hyperpigmentation and obesity. This study aimed to synthesize and evaluate a series of flavonols (1–10) as potential dual enzyme inhibitors.Materials and Methods Ten flavonol derivatives were synthesized and structurally confirmed using spectroscopic techniques. Their inhibitory activities against tyrosinase and pancreatic lipase were assessed through in vitro enzyme assays. Molecular docking and molecular dynamics (MD) simulations were employed to explore binding modes and the stability of enzyme–ligand interactions. Density Functional Theory (DFT) calculations were performed to examine electronic features influencing binding affinity. Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis was used to predict pharmacokinetic properties and drug-likeness.Results The compounds exhibited variable inhibitory activity, with several showing significant dual inhibition. Docking and MD studies revealed stable binding within active sites, highlighting key interactions. DFT results supported structure–activity relationships by correlating electronic parameters with inhibitory potential. ADMET profiles were favorable for most derivatives.Conclusions This is the first study reporting pancreatic lipase inhibition by flavonols alongside their tyrosinase inhibitory potential. These flavonols emerge as promising dual-action candidates for developing treatments targeting obesity and hyperpigmentation.

Aims This study aimed to evaluate the α-glucosidase inhibitory potential of newly synthesized aurone derivatives (1–14) using an integrated experimental and computational strategy, with emphasis on their antidiabetic potential.Materials and methods The compounds were evaluated through in vitro α-glucosidase inhibition and enzyme kinetic assays, along with in vivo studies to assess postprandial glucose control. Molecular docking, MM-GBSA calculations, and molecular dynamics (MD) simulations were performed to analyze interactions with diabetic targets (PDB IDs: 5NN4 and 6KK1). Furthermore, in silico ADME profiling and density functional theory (DFT) analyses were conducted to predict pharmacokinetic properties, drug-likeness, and electronic behavior.Results Several aurone derivatives exhibited strong α-glucosidase inhibition, surpassing standard drugs. Kinetic studies revealed a competitive inhibition mechanism, and in vivo evaluations confirmed their glucose-lowering effects – the first such report for aurones. Computational analyses indicated stable enzyme – ligand complexes with favorable binding affinities and ADME features. DFT results supported the observed structure – activity relationships and highlighted key electronic attributes influencing activity.Conclusions This comprehensive study identifies aurones as potent α-glucosidase inhibitors with significant therapeutic potential, providing a strong foundation for further development of aurone-based antidiabetic agents.

Aims This study investigates the inhibitory potential of a novel series of thioflavonol derivatives (1–12) against α-glucosidase, a key biological macromolecule involved in carbohydrate metabolism, to identify new candidates for type 2 diabetes therapy.Materials and Methods The compounds were evaluated using in vitro enzyme inhibition assays, followed by in vivo antihyperglycemic studies of the most active derivatives. Enzyme kinetics determined the inhibition mechanism, while SAR analysis elucidated structural features governing activity. Computational studies, including molecular docking (PDB IDs: 5NN8 and 8CB1), molecular dynamics simulations, and DFT calculations, explored binding modes and electronic properties. ADMET profiling assessed drug-likeness.Results Several derivatives exhibited strong α-glucosidase inhibition, with the most active compound significantly lowering blood glucose levels in vivo. SAR analysis highlighted key substituents contributing to potency. Docking and MD simulations revealed stable enzyme – inhibitor complexes, and DFT supported favorable electronic interactions.Conclusions This is the first comprehensive study of thioflavonols as α-glucosidase inhibitors, demonstrating their promising biological activity, stable binding behavior, and favorable pharmacokinetic properties, supporting their potential as novel anti-diabetic agents.

Carica papaya seeds, traditionally used in folk medicine, have garnered scientific interest due to their potential therapeutic properties. The study investigates the antioxidant potential and compound composition of Carica papaya seed oil. Utilizing GC–MS analysis, we identified 42 significant compounds in the n-hexane fraction of the oil, with notable constituents including benzyl nitrile (3.43 %), pentadecanoic acid 14-methyl-methyl ester (5.23 %), and n-hexadecanoic acid (7.11 %). The antioxidant activity of the oil was assessed using DPPH radical scavenging assays, revealing a maximum inhibition activity of 61.13 % at a concentration of 100 mg/mL, compared to 76.23 % for the standard vitamin C. For further precise binding pose predictions, Schrödinger's Glide module was used for molecular docking. Docking scores and molecular interaction profiles were used to evaluate binding interactions after the produced ligands were docked into the receptor grid. The greatest docking score (−6.657) was shown by 6-chloro for 5B6N, 1H-Indole-2-carboxylic acid, which formed hydrogen bonds with PHE 207 and VAL 187, two essential residues for ligand stabilization. Further, the molecular dynamics simulation study disclosed that the complexes of the relatively active phytoconstituents with the target structures were stable. These findings highlight the therapeutic potential of Carica papaya seed oil as a natural antioxidant, suggesting its viability for further research and application in health-related fields.