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Pyridine-linked 1,3,4-oxadiazoles decorated with secondary amines as α-amylase inhibitors: Synthesis, crystal structure, enzyme kinetics and computational studies
No full textA new series of pyridine-linked 1,3,4-oxadiazole derivatives (5a–5j) incorporating different secondary amines were synthesized in good yields (80–92 ) and their structures confirmed by 1H and 13C NMR spectroscopy and mass spectrometry. Biological screening revealed that compound 5c displayed the strongest α-amylase inhibition with an IC₅₀ of 106.1 ± 1.21 µM, compared with the standard drug acarbose (35.8 ± 1.25 µM). Enzyme kinetic studies (Lineweaver-Burk analysis) demonstrated that 5c acts through a non-competitive inhibition mechanism, increasing Km from 27.36 µM (control) to 135.77 µM, while reducing Vmax from 1.55 µM min−1 to 0.135 µM min−1. The structure of 5c was further validated by single-crystal X-ray diffraction, and Hirshfeld surface analysis highlighted key intermolecular interactions, predominantly H···H (45.1 ), H···N (18.4 ), and H···C (12.6 ). Density Functional Theory calculations at the B3LYP/6–311+G(d,p) level reproduced the crystal geometry and indicated a HOMO-LUMO gap of 3.898 eV, consistent with moderate electronic reactivity. Molecular docking revealed that Compound 5c showed strong α-amylase binding with docking energies of -7.7 to -8.0 kcal mol−1 outperforming reference inhibitor acarbose and indicating superior inhibitory efficacy. ADME profiling supported the drug-like nature of 5c (MW = 323.35 g·mol−1, logP = 0.42, TPSA = 84.07 Ų, zero Lipinski violations), suggesting good oral bioavailability. Collectively, these experimental and computational findings identify 5c as a promising lead scaffold for the design of new antidiabetic agents
Influence of mono- and di-bromo substitution on the structure conformation and supramolecular assembly of schiff base derivatives
No full textThe positioning of substituents plays a critical role in dictating molecular conformation and supramolecular assembly, essential for the rational design of functional crystalline materials. In this work, two Schiff base compounds were synthesized via the condensation of ethyl 2-aminoisonicotinate with 3‑bromo-5-hydroxybenzaldehyde and 3,5-dibromo-5-hydroxybenzaldehyde. Single crystals suitable for X-ray diffraction were obtained by slow evaporation, and both compounds crystallized in the triclinic space group P̅1. Structural analysis revealed nearly planar geometries with dihedral angles between the hydroxyphenyl and ethoxypyridyl moieties, connected through an azomethine bridge. The planarity facilitated robust π–π stacking interactions and hydrogen bonding, both contributing to crystal packing stabilization. Comparative assessment showed that the second bromine atom significantly modifies intermolecular interactions and supramolecular organization. Hirshfeld surface, fingerprint plots, enrichment ratios, and QTAIM analyses quantitatively characterized these contacts, while DFT calculations indicated enhanced π-electron delocalization and reduced HOMO–LUMO gaps. Molecular docking against Staphylococcus aureus TyrRS revealed π-stacking-mediated ligand–receptor interactions with good binding energies, highlighting biological relevance. This study provides quantitative insight into how positional substitution governs molecular packing, noncovalent interactions, and protein-ligand interaction leading to the potential functional applications
Design, synthesis, and mechanistic insights into the anti-proliferative activity of Novel N9-substituted harmine derivatives
No full textTo explore the therapeutic promise of harmine chemistry, the two novel derivatives 3a and 3b were synthesized through N-alkylation of plant-derived harmine using sodium hydride and the corresponding halide precursors (2a and 2b) in dimethylformamide at room temperature. Structural characterization was performed using ¹H NMR, ¹³C NMR, and HRMS analyses. Density Functional Theory (DFT) calculations were employed to investigate the stability and molecular properties of the synthesized derivatives. Further, the compounds were tested for anti-proliferative activity against breast cancer cell lines (MCF-7 and MDA-MB-231) and for cytotoxicity against the Human Embryonic Kidney derived HEK-293T cell line. Their ability to suppress the expression of proliferation-associated genes (ER, Ki67 and AGR2) was examined, supported by molecular docking studies against key oncogenic targets (CAD, mPGES-1, and CTLA-4). Compound 3a exhibited stronger growth-inhibitory effects (IC₅₀: 27.94 ± 0.96 µM) compared to 3b, with lower toxicity toward normal cells. ADMET predictions suggested good oral bioavailability and minimal mutagenic or carcinogenic risk. These results indicate that N9-substituted harmine derivatives hold promise for further development as anti-breast cancer agents
Crystal-guided computational profiling of dichlorophenyl-piperazine ligands as JNK3 binders: Hydrophobic interaction-driven design for neurodegenerative therapy
No full textThe present work reported a comprehensive structural, electronic, and biological evaluation of two novel heterocyclic compounds, KDM1 and KDM2, featuring a 2,3-dichlorophenyl piperazine moiety, as c-Jun N-terminal kinase 3 (JNK3) binders with potential applications in treating neurodegenerative and neuroinflammatory disorders. Single-crystal X-ray diffraction confirmed the crystallization of KDM1 in the orthorhombic Pbca space group and KDM2 in the monoclinic C2/c space group. Both structures exhibited prominent hydrogen-bonding and halogen-mediated supramolecular networks. Quantum Theory of Atoms in Molecules (QTAIM) and Non-Covalent Interaction (NCI) analyses revealed that weak van der Waals forces. Density Functional Theory (DFT) computations provided insights into the electronic properties, highlighting the chemical stability and intramolecular delocalization within each compound. Molecular docking studies indicated strong binding affinity of KDM1 and KDM2 to the JNK3 active site, largely driven by hydrophobic and van der Waals interactions within the ATP-binding cleft. Molecular dynamics (MD) simulations further validated the stability of the ligand–JNK3 complexes, with root mean square deviation (RMSD), root mean square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration analyses confirming minimal structural deviation. MM-GBSA free energy calculations supported the thermodynamic favorability of ligand binding. Comparative MD simulations with apo-JNK3 reinforced the role of the ligands in stabilizing the enzyme structure. ADME profiling indicated favorable pharmacokinetic properties for both compounds. Overall, this multistage investigation underscores the therapeutic potential of KDM1 and KDM2 as JNK3 binders and offers molecular-level insights into their supramolecular behavior, guiding the design of next-generation neuro-protective agents
Role of free volume on nonlinear optical properties of PSAN/NiO polymer nanocomposites
No full textThis research investigates the nonlinear optical (NLO) properties of Poly (styrene-co-acrylonitrile) (PSAN) /Nickel Oxide nanoparticles (NiO) polymer nanocomposites (PNCs) at various (NiO) nanoparticles wt (0.0, 0.2, 0.4, 0.6, 0.8 and 1.0). This study employs analytical techniques to examine the influence of NiO nanoparticles on the microstructure and nonlinear optical behavior of PSAN/NiO PNCs. The results reveal that PSAN/NiO PNCs at 1.0Â wt of NiO nanofiller loading exhibit lowest energy band gap, bigger free volumes and highest nonlinear optical parameters. The reduced energy band gap due to localized energy states which increase the probability of two-photon absorption (TPA) and enhance the nonlinear optical absorption. Similarly, bigger free volumes promotes the dipole polarization by accommodating dipole orientation w.r.t the applied optical field. The PSAN/NiO PNCs with 1.0Â wt of NiO nanofiller loading demonstrates strong optical limiting due to the two-photon absorption and defocusing effects
Highly selective ammonia gas sensor using Ga2O3/MoO3 nanocomposite at ambient atmospheric conditions
No full textThe β-Ga2O3 and MoO3 nanocomposite with varying concentration of MoO3 at 2.5 , 5 and 7.5 were synthesized through hydrothermal method followed by physical mixing. Obtained nanocomposites were characterized to study its morphological, structural and optical properties through XRD, SEM, EDAX, TEM, XPS and UV–Visible spectroscopy. Surface area analysis was done using BET analysis method. Ammonia (NH3) sensing studies were conducted at room temperature for synthesized composites. Nanocomposite with increased MoO3 concentration showed increase in the response towards ammonia detection and highest response of 420.12 for 100 ppm NH3 at relative humidity (RH) of 69 with response and recovery time of 53.75 s and 27.44 s respectively. Studies on humidity dependent sensing have been conducted for the same synthesized nanocomposites. The enhanced sensing of NH3 in room temperature is attributed to sensing mechanism mediated by the adsorbed humidity and oxygen on the surface of the sensing material in addition to the chemical and electronic sensitization effects
Design of innovative nitrogen-doped carbon quantum dots integrated with magnetic nanocomposite barium ferrite for enhanced supercapacitors electrode performance
No full textNitrogen-doped carbon quantum dots (NCQDs) have garnered considerable interest in energy storage applications owing to their remarkable electrical characteristics and surface adaptability. In this regard, barium ferrite (BFO) nanocomposites with NCQDs have been incorporated due to their remarkable electrochemical performance in supercapacitors. Where NCQDs with an average particle size of about 3Â nm were prepared using a simple hydrothermal approach and then combined with barium ferrite (BFO) to create a novel magnetic nanocomposite (BFO@NCQDs). The NCQDs functioned as structure-directing agents, facilitating exact regulation of the size, crystallinity, and shape of the BFO nanoparticles. The structural and morphological characteristics of the synthesized nanocomposite were thoroughly characterized using PXRD, Raman spectroscopy, FTIR, FE-SEM, and HRTEM. Magnetic studies revealed a saturation magnetisation (Ms) of 50.59Â emu/g and a notably increased specific surface area (SABET) of 821.65Â m2/g. Electrochemical assessments in a 5Â M KOH electrolyte using a three-electrode configuration demonstrated exceptional performance, attaining a specific capacitance (Cs) of 1513.94Â F/g at a scan rate of 5Â mV/s, by ascertained using cyclic voltammetry. Galvanostatic charge/discharge analysis confirmed a high specific capacitance of 1984.98Â F/g at a current density of 2 A/g. The electrode exhibited remarkable energy and power densities, achieving 42.805Â Wh/kg and 7565.43Â W/kg, respectively, while sustaining a power density of 2090.39Â W/kg at peak energy output. The electrode material exhibited exceptional cycling stability, maintaining 91.1Â of its capacitance after 10,000Â cycles at 12 A/g. The findings underscore BFO@NCQDs as an economical, highly conductive, and resilient electrode material, positioning it as a viable option for next-generation supercapacitors and portable electronic applications
Multifaceted exploration of benzyl 5-(p-tolyl)-1,3,4-thiadiazole-2-carboxylate: Spectroscopic, structural, and computational insights into its drug-like potential
No full textThe present research article delves into a comprehensive structural study of a thiadiazole derivative. The work begins with the synthesis by employing a multifaceted approach to unravel its molecular properties and potential biological significance of a novel thiadiazole derivative benzyl 5-(p-tolyl)-1,3,4-thiadiazole-2-carboxylate (C1) synthesized using cyclocondensation reaction. A single crystal X-ray diffraction study revealed that the compound (C1) crystallized in the triclinic crystal system with P 1¯ space group, revealing a non-planarity of the structure. The crystal packing is stabilized by a network of intermolecular interactions, including hydrogen bonds, CH…O, CH…π, and π-π stacking, Van der Waals force and other intra-intermolecular interaction. The Hirshfeld surface analysis was performed, in order to visualize, explore and quantify the inter molecular interactions that stabilize the crystal packing of the compound (C1), which reveals that H…H contacts are major contributors to the total Hirshfeld surface. Density Functional Theory (DFT) was employed using the B3LYP functional and 6–311++ G (d, p) basis set to explore the compound’s electronic structure and physicochemical properties. The energy gap of the compound C1 is found to be 4.272 eV. Molecular Electrostatic Potential (MEP) surfaces were performed to get additional insights into charge distribution, intermolecular interactions, and stabilization energies. Quantum theory of atoms in molecule (QTAIM) and non-covalent interactions (NCI) analysis provided insights into the topology of the compounds. Based on the Bader’s theory, reduced density gradient (RDG) analysis is exploited to visualize and quantify the concept of electronic compactness in supramolecular chemistry, and to investigate the nature and strength of the van der Waal interactions. Additionally, molecular docking studies are used to compare the titled compound (C1) with a standard drug. The binding energy of the complex 7WWK-C1 protein is found to be -8.73 kcal/mol. According to the in silico simulations, the molecule being studied may ultimately be a good inhibitor for SARS-CoV-2 virus main protease, and additional in vitro and in vivo research may reveal its therapeutic potential
Multimodal cell death induced by indirubin-3′-oxime through inhibition of Akt/mTOR axis in lung cancer cells
No full textLung cancer is a major type of malignancy that has contributed to a high mortality rate for many years. Discovering new small molecules with strong cytotoxic effects on lung cancer is crucial for developing new therapies. In this study, we describe the synthesis of a novel triazole-indirubin-3′-oxime derivative (designated as CRM1) and examine its ability to induce distinct forms of cell death, as well as elucidate the cytotoxicity-associated molecular mechanisms in lung cancer cells. CRM1 selectively reduced cell viability in lung cancer cell lines (A549, PC9, and H1299) without significantly affecting the viability of normal lung cells (HEL299). Mechanistic investigations have demonstrated that CRM1 induces paraptosis through the downregulation of Alix and the upregulation of ATF4 and CHOP. This process is associated with disruption of mitochondrial membrane potential, induction of endoplasmic reticulum stress, and accumulation of reactive oxygen species (ROS). CRM1 was observed to induce apoptosis, as indicated by DNA fragmentation, an increase in Sub-G1 cell population, as well as elevated caspase-3 cleavage and Bax expression. CRM1 also promoted autophagy, as evidenced by increased expression of Atg7, phosphorylated Beclin-1, and LC3-II, as well as enhanced autophagosome formation. Pharmacological inhibition studies confirmed the independent induction of apoptosis, paraptosis, and autophagy. Pre-exposure of cancer cells to N-acetyl cysteine abrogated CRM1-induced cytotoxicity. Mechanistic studies demonstrated that CRM1 suppresses the activation of Akt, mTOR, and p70S6K, while the overexpression of Akt counteracts the CRM1-driven cytotoxic effects. CRM1 also synergistically potentiated the cytotoxic efficacy of paclitaxel by co-targeting multiple cell death processes. Collectively, these results suggest CRM1 as a promising cytotoxic candidate with a multimodal mechanism of action in lung cancer cells