The Staudinger reaction, first reported by Hermann Staudinger in 1907 as a ketene-imine [2+2] cycloaddition for the synthesis of β-lactams, has evolved into one of the most versatile transformations in modern organic synthesis. Beyond its classical applications in β-lactam formation and azide reduction to primary amines, the reaction now includes several advanced methodologies with broad applications in medicinal chemistry, chemical biology, and materials science. This review summarizes the evolution of the Staudinger reaction from its classical forms to recent developments, including metal-free microwave-assisted Wolff-Staudinger cascade reactions, continuous-flow multicomponent strategies, and ketene generation through toluenesulfonyl chloride (TsCl)-mediated activation. It also highlights the use of Staudinger-based methodologies, such as Staudinger-aza-Wittig, Ugi-Staudinger, and asymmetric catalytic sequences, for the efficient synthesis of five- and six-membered heterocycles, complex alkaloids, and chiral nitrogen-containing compounds. Particular emphasis is placed on compounds reported between 2020 and 2026, with a comparative evaluation of synthetic methodologies, reaction yields, stereochemical outcomes, and biological activities. The review further discusses the pharmaceutical significance of Staudinger-derived molecules, including β-lactam antibiotics that inhibit penicillin-binding proteins, as well as applications in glycobiology, biomolecular labeling, and cancer research. Collectively, these advances demonstrate the continued importance of the Staudinger reaction as a powerful and adaptable platform for the synthesis of biologically relevant molecules and advanced functional materials.

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 IC50 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 IC50 = 0.95–1.60 µM; BChE IC50 = 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 IC50 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.

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 (IC50 = 7.8 ± 2.2 µM), 6 (IC50 = 10.2 ± 1.1 µM), and 5 (IC50 = 13.4 ± 1.9 µM) exhibiting stronger activity than acarbose (IC50 = 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.

A series of chalcone-sulfonate ester derivatives (1-7) were synthesized and evaluated for their potential inhibitory activity against urease and α-amylase enzymes. The chemical structures of the synthesized compounds were confirmed using appropriate spectroscopic techniques (IR, NMR and mass spectrometry). The biological potential of these derivatives was assessed through in vitro enzyme inhibition assays, where several compounds demonstrated promising activity against both urease and α-amylase, suggesting their possible application in the management of urease-related infections and disorders associated with carbohydrate metabolism. Structure-activity relationship (SAR) analysis revealed that the nature and position of substituents on the aromatic rings significantly influenced the inhibitory potency of the compounds. To further understand the interaction mechanisms, molecular docking studies were performed to investigate the binding modes of the synthesized molecules within the active sites of the target enzymes. In addition, pharmacokinetic properties were evaluated through in silico ADME analysis to assess drug-likeness and potential bioavailability. Furthermore, molecular dynamics (MD) simulations were carried out to examine the stability and dynamic behaviour of the ligand-enzyme complexes, while density functional theory (DFT) calculations were employed to explore the electronic characteristics and reactivity parameters of the compounds. The integrated experimental and computational findings highlight the potential of chalcone-sulfonate esters as promising scaffolds for the development of novel urease and α-amylase inhibitors.

AIMS:This study aimed to evaluate the behavioral and biochemical effects of synthesized flavonols (1-10) 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: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. CONCLUSIONS: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.

Neurological disorders such as Alzheimer's disease and epilepsy are complex, multifactorial conditions that require therapeutic agents capable of acting through multiple mechanisms. In the present study, a series of structurally diverse flavonol analogues was synthesized and evaluated for their dual cholinesterase inhibitory and anticonvulsant potential through integrated in vitro, in vivo, and in silico approaches. The compounds were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities using standard spectrophotometric assays. Selected derivatives demonstrating significant enzyme inhibition were further assessed for anticonvulsant efficacy in maximal electroshock seizure (MES) and pentylenetetrazole (PTZ)-induced seizure models. Several compounds exhibited noteworthy inhibition of both cholinesterase enzymes, with the most active derivatives displaying low micromolar potency. In anticonvulsant studies, the leading compounds produced dose-dependent protection against electrically and chemically induced seizures, significantly reducing seizure severity, prolonging seizure latency, and increasing protection rates in both experimental models. To the best of our knowledge, this is among the first reports evaluating the anticonvulsant activity of this specific flavonol scaffold in both MES and PTZ models. Computational investigations, including induced-fit docking, MM-GBSA binding free-energy calculations, molecular dynamics simulations, ADME prediction, and density functional theory (DFT) analyses, revealed favorable enzyme-binding interactions, stable ligand-protein complexes, and acceptable drug-like characteristics. The convergence of biological and computational findings identified compound 8 as the most promising multifunctional candidate, exhibiting potent dual cholinesterase inhibition, pronounced anticonvulsant activity, and sustained target engagement. These results demonstrate that flavonol-based scaffolds represent attractive lead structures for the development of multifunctional therapeutic agents targeting neurodegenerative disorders and epilepsy.

This work presents a comprehensive study of five chalcones using synthetic, spectroscopic (1H and 13C-NMR), spectrophotometric (UV-Vis), electrochemical, and theoretical (DFT) approaches. UV-Vis spectroscopy revealed that substituent effects induce a red shift in the lowest-energy pi-pi* electronic transition. NMR spectroscopy and mass spectrometry confirmed the structures of the synthesized chalcones, while DFT calculations provided insight into their geometries, E-Z isomerization, and isomer distribution. Results obtained from gas phase DFT calculations, or in either acetonitrile or DMSO (implicit solvent model) gave similar optimized geometries and electronic structures for the chalcones. A clear correlation was observed between the carbonyl 13C-NMR spectroscopic chemical shifts and the reduction potentials: more electron-rich (shielded) carbonyl carbons exhibit more negative reduction potentials, indicating reduced ease of electron acceptance. Chalcones lacking a 2-hy-droxy group showed a direct relationship between experimental reduction potentials and DFT-calculated lowest unoccupied molecular orbital energies, whereas 2-hydroxy-substituted chalcones followed a distinct trend. A comparative analysis of the experimental and theoretical data revealed good agreement, thereby validating the computational models.

Triphenylenes are a class of polycyclic aromatic hydrocarbon that have been attracting increasing attention owing to their widespread applications in areas such as liquid crystals, organic electronics, photovoltaics, light emitting diodes, and catalysts. The utility of triphenylenes stems from their flatness, rigidity, and aromatic nature. This review provides an exploration of triphenylene derivatives, with an emphasis on recent advancements in their synthesis, properties, and multifaceted applications. Highlighting their synthetic strategies, we discuss both classical methods and modern approaches, including metal-catalyzed reactions and photochemical techniques, which have enabled the development of a wide range of substituted triphenylenes, as well as their dimers, trimers, twinned molecules, and oligomers. The electronic structure of triphenylene, characterized by a delocalized π-electron system, underpins its remarkable charge transport properties. In terms of applications, triphenylene-based liquid crystals are particularly notable for forming columnar mesophases with highly ordered structures, facilitating advantageous macroscopic molecular orientation. These properties underscore its potential for next-generation functional materials across diverse domains, including organic electronics, photovoltaics, light-emitting diodes, and catalysis. By integrating insights into its properties and future potential, this review aims to provide a valuable resource for researchers investigating triphenylene and its derivatives.

Thiophene-2-based carboxamides have emerged as valuable scaffolds in the search for new anticancer drugs. In this work, various thiophene-2-carboxamides (1a-d, 2 and 3) were prepared by reacting thiophene-2-chloride with a range of aliphatic and aromatic amines. N-alkylation of N-(pyridin-3-yl) and N-(pyridin-4-yl) thiophene-2-carboxamides (1b and 1c) with different alkyl halides yielded compounds 4a–e and 5a–b. Their structures were confirmed by FT-IR, 1H NMR, and 13C NMR analyses, with X-ray crystallography of 4e, which revealed a monoclinic lattice in the Cc space group. The synthesized compounds were tested for cytotoxic effects on cancer (MCF-7, T47D, HeLa) and normal (Vero) cell lines. All the compounds were less toxic against Vero, whereas 1c, 2, 3, 4a, 4c, 4e and 5b showed high sensitivity towards HeLa cell line. 4a was also sensitive to MCF-7 and T47D cell lines with IC50 of 15.3 μM and 14.7 μM, respectively.Notably, 4d and 5b demonstrated the minimal IC50 values of 9.10 μM and 7.10 μM, respectively, in comparison to all other compounds evaluated against the HeLa cell line. Apoptotic mode of cell death was analyzed by using Annexin V-FITC assays. DFT, molecular docking, and QSAR analysis offered a detailed analysis of the geometry, electronic distribution and strong binding affinity of studied compounds to the JAK2 inhibitor. DNA interaction of studied compounds was carried out via UV–Vis, Viscometric analysis and electrochemical methods, which revealed a mixed mode of interaction characterized by a moderate to strong binding affinity.

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.

Five flavonols bearing electron-donating and electron-withdrawing substituents were synthesized and characterized by NMR spectroscopy, mass spectrometry, UV-Vis spectroscopy, and cyclic voltammetry. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed to investigate their molecular geometries, frontier molecular orbitals, electronic structures, and excited-state properties. The optimized geometries revealed that flavonols containing substituents at both the C2' and C6' positions adopt non-planar conformations, whereas the remaining derivatives are essentially planar. Potential energy surface calculations showed that steric interactions between the 3-hydroxyl group and the ortho substituents stabilize the twisted conformations and reduce π-conjugation. The HOMOs were predominantly localized on rings B and C, while the LUMOs were distributed over rings A and C, indicating similar oxidation and reduction centres throughout the series. Electron-donating substituents raised the HOMO energies, resulting in lower oxidation potentials and red-shifted UV-Vis absorption bands. TDDFT calculations accurately reproduced the experimental absorption spectra and confirmed that the lowest-energy electronic excitation is dominated by the HOMO→LUMO transition. Strong correlations were observed between the experimental electrochemical energy gap and the DFT-calculated HOMO-LUMO energy gap (R2 = 0.92), while excellent agreement was obtained between the calculated and experimental absorption maxima (R2 = 0.98). The excellent agreement between experimental and computational parameters establishes quantitative structure-electronic property relationships for flavonols by integrating DFT, TDDFT, UV-Vis spectroscopy and electrochemistry, and provides a predictive basis for the rational design of flavonol-based functional materials and biologically active derivatives.

Metal phthalocyanines (MPcs) have emerged as promising redox-active materials for next-generation electrochemical energy storage owing to their tunable electronic structures, reversible multi-electron redox behavior, high chemical stability, and versatile coordination chemistry. This review critically summarizes recent advances in MPc-based electrode materials for rechargeable batteries and supercapacitors during 2022–2026, with particular emphasis on structure-property relationships, molecular engineering strategies, electrochemical mechanisms, and artificial intelligence (AI)-assisted materials design. Recent studies demonstrate that hybridization of MPcs with conductive carbon materials, conductive polymers, and metal–organic frameworks significantly enhances electrical conductivity, ion transport, and electrochemically active surface area, leading to remarkable improvements in electrochemical performance. Representative MPc-based electrodes have achieved reversible capacities exceeding 1080 mAhg−1 in lithium-ion batteries, specific capacitances up to 824 Fg−1 in supercapacitors, energy densities of 86.2 Whkg−1, and cycling stability of up to 100,000 charge–discharge cycles, highlighting their considerable potential for high-performance energy-storage applications. Furthermore, density functional theory, molecular dynamics simulations, and operando characterization have provided valuable insights into charge-storage mechanisms and redox processes, while AI and machine learning are emerging as powerful tools for accelerating molecular design and performance optimization. Despite these advances, challenges associated with intrinsic electrical conductivity, molecular aggregation, electrolyte compatibility, and scalable device fabrication remain.

Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that play essential roles in physiological processes and are recognized as important therapeutic targets for disorders such as glaucoma, epilepsy, and cancer. In this study, a series of azo-linked chalcone derivatives (1-10) was designed, synthesized, and evaluated for their inhibitory activity against human carbonic anhydrase isoforms I and II (hCA I and hCA II). All compounds demonstrated strong inhibitory activity in the low nanomolar range, with several derivatives surpassing the reference drug acetazolamide in potency. Remarkably, compound 1 exhibited the highest activity, particularly against hCA II, highlighting its potential as a lead candidate. Structure-activity relationship (SAR) analysis indicated that both the azo-linked aromatic moiety and the substitution pattern on the chalcone ring play critical roles in determining activity. Molecular docking studies revealed favorable binding interactions within the active site of the enzyme, which were further validated by molecular dynamics (MD) simulations conducted over 250 ns. In addition, in silico ADMET profiling suggested that the synthesized compounds possess acceptable pharmacokinetic properties, including good oral bioavailability, membrane permeability, and low predicted toxicity, supporting their drug-likeness. Hence, these findings demonstrate that azo-chalcone hybrids constitute a promising scaffold for the development of potent carbonic anhydrase inhibitors, with compound 1 identified as a strong candidate for further optimization and preclinical investigation.

Diabetes mellitus is a chronic metabolic disorder associated with persistent hyperglycemia and the development of numerous secondary complications. In the present study, a series of 4-aminochalcone derivatives (1N-10N) were synthesized and evaluated as potential dual inhibitors of α-glucosidase and aldose reductase using integrated in vitro, in vivo, and in silico approaches. The synthesized compounds were screened for their inhibitory activities against both target enzymes. Several derivatives exhibited remarkable inhibitory activity, displaying nanomolar IC50 values against α-glucosidase and micromolar IC50 values against aldose reductase, demonstrating the suitability of the 4-aminochalcone scaffold for dual-target antidiabetic drug development. The antidiabetic potential of the most active compounds was further investigated in streptozotocin-induced diabetic rats. To the best of our knowledge, this represents the first report describing the evaluation of 4-aminochalcone derivatives as aldose reductase inhibitors and their subsequent in vivo 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.

Three hydrazone-chalcone hybrid compounds (1-3) were synthesized and investigated using spectroscopic, electrochemical, and computational methods. UV-Vis spectroscopy and TD-DFT calculations reveal two main absorption bands: a low-energy band at 480-500 nm arising from a hydrazone-localized HOMO -> LUMO (it -> it*) transition, and higher-energy bands (300-350 nm) associated with chalcone-centered excitations. Cyclic voltammetry shows a first diffusion-controlled reduction near-1.3 V vs. Fc/Fc+, significantly less negative than for simple chalcones, indicating hydrazone-based reduction, followed by a second chalcone-centered reduction at more negative potentials. The reduction potentials correlate inversely with DFT-calculated LUMO energies, consistent with sequential electron addition to hydrazone-and chalcone-centered orbitals. These results demonstrate that the hydrazone moiety governs the optical and redox behaviour of these hybrids, while chalcone substituents modulate higher-energy transitions.

Azo-based metal complexes have emerged as versatile coordination systems exhibiting tunable optical, electronic, and redox properties. This review summarizes recent progress in their structural design, synthetic methodologies, and functional characteristics. Key aspects include the influence of substituents, conjugation, and metal coordination on the electronic structure and chelation behavior of azo ligands. Various synthetic approaches such as diazotization–coupling, metal-templated assembly, heterocyclic and Schiff-base derivatization, and green or microwave-assisted techniques are discussed. For the first time, this review systematically discusses both photophysical and electrochemical parameters of azo-based metal complexes reported between 2021 and 2025 within a unified framework. Spectroscopic and computational analyses are highlighted for elucidating coordination modes and electronic transitions. Particular attention is given to their photophysical and electrochemical behavior, including metal–ligand charge transfer, photoisomerization, and redox responsiveness. The structure–property correlations are further linked to practical applications in light-emitting materials, molecular switches, sensors, photocatalysis, and electrochromic devices. Finally, current challenges and emerging directions are outlined to guide the rational design of multifunctional azo–metal complexes for advanced optoelectronic and energy-related technologies.

Flavonoids represent a structurally diverse class of naturally occurring polyphenolic compounds widely distributed in plants and recognized for their broad spectrum of pharmacological activities. Among these, their anticancer potential has gained considerable attention due to their ability to modulate multiple molecular targets involved in tumour initiation and progression. This review comprehensively covers recent advances reported during the period 2024-2026, focusing on flavonoids as promising anticancer agents with emphasis on their structural diversity, synthetic accessibility, and mechanistic pathways. Various subclasses, including flavones, flavonols, and chalcones, are discussed in relation to their chemical frameworks and biological functions. A detailed account of classical and modern synthetic strategies is presented, including the Algar-Flynn Oyamada, Baker-Venkataraman, Allan-Robinson, Kostanecki, and Claisen-Schmidt methodologies, along with emerging approaches such as transition-metal catalysis, microwave-assisted synthesis, and green chemistry techniques. These methods enable the efficient generation of structurally diverse flavonoid derivatives with improved pharmacological profiles. Recent advances in structure-activity relationship (SAR) studies highlight the critical role of substituent patterns, electronic effects, and hybrid pharmacophores in enhancing anticancer activity. Furthermore, numerous synthetic flavonoid derivatives and hybrids have demonstrated potent cytotoxic activity in vitro, often surpassing standard chemotherapeutic agents. Despite promising preclinical outcomes, clinical translation remains limited due to challenges such as poor bioavailability and rapid metabolism. Current research efforts focusing on structural modification and advanced drug delivery systems are expected to overcome these limitations.

Vanillin sulfonate derivatives are an important class of functional organic compounds with promising applications in materials science and molecular design. In this study, vanillin sulfonate derivatives (1–9) bearing halogen (F, Cl, Br), nitro (NO2), and methoxy (OCH3) substituents were investigated using a combined experimental and computational approach. Density functional theory calculations were performed at the B3LYP/6-31G(d, p) level to evaluate their structural stability, electronic properties, vibrational behavior, and chemical reactivity. The optimized geometries and total electronic energies revealed that both the type and position of substituents strongly affect molecular stability, with the p-brominated derivative exhibiting the highest stability at -3886.04 a.u, while the nitro-substituted compound showed enhanced electronic activity. Frontier molecular orbital analysis indicates energy gaps ranging from 4.03 to 4.95 eV, suggesting differences in charge-transfer ability and kinetic stability among the compounds studied. Furthermore, global reactivity descriptors indicated that the nitro-substituted derivative exhibits the highest softness and electrophilicity, with a value of 2.96 eV for compound 9, indicating superior electron-accepting capability. Experimental FT-IR, NMR, and mass spectrometric techniques showed excellent agreement with theoretical predictions, confirming the reliability of the computational model. ELF, LOL, and NCI-RDG analyses provided detailed insight into electron localization and covalent bonding at C–C, C–N, C–O, C–Br, and C–Cl bonds, steric effects near aromatic carbons, and weak intermolecular interactions close to C–O, Cl–O, O–S and C–S links.