A new series of amide derivatives of pyridine-1,2,4-triazoles (10a–j) was synthesized and exhaustively studied using 1H NMR, 13C NMR, and mass spectrometry. The synthesized compounds were investigated for their in vitro anticancer activity against five human cancer cell lines namely PC3 and DU-145 (prostate), NCI-H460 (lung) and HCT-116 and HCT-15 (colon) by the MTT assay. Etoposide was used as a positive control for comparison. Most of synthesized compounds showed potential cytotoxic action with IC50 values ranging from 0.17 ± 0.045 to 5.73 ± 0.44 µM, while etoposide showed IC50 values from 1.38 ± 0.28 to 3.21 ± 0.15 µM. The derivatives 10a, 10b, 10c and 10j compounds showed better anticancer activity. In particular, the compound 10j was the most active analogue, exhibiting exceptional cytotoxicity against all five cancer cell lines. These results suggest that pyridine-1,2,4-triazole amide derivatives could be suitable leads for development of new anticancer drugs..
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which disease-modifying therapies remain an unmet clinical need. Dysregulated acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) impair cholinergic neurotransmission, promoting cognitive decline and neurodegeneration. Here, we report on the design and synthesis of a new series of thiazole-based thiazolidinone compounds as dual cholinesterase inhibitors. Kinetic inhibition studies revealed that compounds 6 and 7 exhibited low-micromolar potency against both targets (IC50 = 5.28 µM and 4.12 µM against AChE; 7.93 µM and 4.96 µM against BuChE, respectively), as compared to donepezil. Moreover, computational analyses demonstrated favorable predicted molecular docking score of compounds 1, 2, 6 and 7 against BuChE and AChE) that confirmed stable ligand-enzyme complexes with persistent key interactions throughout molecular docking and compatibility with the target enzymes. Hence, these data identify as structurally differentiated, potent and promising cholinesterase inhibitors.
The crystal structure of both I and II has been determined. The asymmetric unit of, C12H8Cl2N2OS, I, and C20H16Cl2N2OS, II, consists of one independent molecule. The molecular structure composed of planar 2-oxo-1,2-dihydropyridine-3-carbonitrile as the central moiety that makes dihedral angles of 36.77 and 36.89° with the benzene (C10–C15) and the thiophene (S1/C6–C9) rings, respectively, in II, and rotated to the thiophene ring by a dihedral angle of 40.31° in I. In the crystal I, the molecules are connected by N—H···O, C—H···N hydrogen bonds, π-π stacking interactions and C—Cl···Cl halogen bonds. Molecules in II, are connected by N—H···O hydrogen bonds, C—Cl···N halogen bonds and π-π stacking interactions in the structure. The Hirshfeld surface analysis for both compounds was used to visualize intermolecular interactions along with energy calculations.
High-quality single crystals of a new chalcone derivative (2E)-3-(2-methylphenyl)-1-(3-nitrophenyl)prop-2-en-1-one (2MNP) were grown by slow solvent evaporation technique. Spectroscopic analyses confirm the functional groups and the purity of the chalcone. Single-crystal X-ray diffraction studies revealed a monoclinic crystal structure with space group P21/c. Hirshfeld surface analysis and two-dimensional fingerprint plots were employed to quantify the intermolecular contacts governing the crystal packing. For the theoretical calculations, the 2MNP molecule was optimized at the minimum potential energy using Gaussian 09 software at the B3LYP/6-311++G(d,p) level. Both ground-state and excited-state geometries were obtained for the DFT and TD-DFT calculations. The Structural assignment and vibrational contribution of the functional group were assigned with PED percentage. All calculated results were in good agreement with experimental values. UV–Visible–NIR spectroscopy revealed an experimental optical band gap (3.05 eV), which is in agreement with the HOMO-LUMO energy gap (3.4971 eV). The polarization characteristics of the molecule were studied through atomic charge distribution analysis, and reactive sites on the molecular surface were studied using MEP. Thermal analysis confirmed a melting point of 111.5 °C. The third-order nonlinear optical response at 532 nm exhibited reverse saturable absorption and self-defocusing behavior, with a nonlinear absorption coefficient of 2.55 × 10⁻⁶ cmW⁻¹ and a nonlinear refractive index of −9.40 × 10⁻¹⁰ cm²W⁻¹. A third-order susceptibility of 0.54 × 10⁻⁷ esu and an optical limiting threshold of 3.35 kJ cm⁻² were obtained. These results demonstrate that 2MNP possesses favorable structural, optical, thermal, and third-order nonlinear optical characteristics, highlighting its potential for applications in nonlinear optical and optical-limiting systems.
The self-aggregation behaviour of pyrrolidinium-based surface-active ionic liquid (SAIL), [C₁₄C₁pyrr][Br], in aqueous solutions of citric acid-based deep eutectic solvents (DESs) was investigated. The DESs were prepared by mixing citric acid with polyethylene glycol (PEG-400) and ethylene glycol (EG), respectively and characterized by FTIR and DSC. The critical micelle concentration (CMC) and molecular interactions of the SAIL in the DESs were examined using conductivity, surface tension, and FTIR spectroscopy. The thermodynamic parameters of self-aggregation, namely the standard enthalpy of micellization (ΔH°ₘ), standard Gibbs free energy of micellization (ΔG°ₘ), and standard entropy of micellization (ΔS°ₘ), were evaluated from the temperature dependence of the CMC over 298.15–313.15 K, to better understand the self-aggregation behaviour of the SAIL in aqueous DES media. The self-aggregation behaviour of the SAIL in aqueous DES solutions of different concentrations was further investigated using surface tension measurements at 298.15 K. The molecular interactions between the SAIL and DESs responsible for the observed changes in micellar behaviour were elucidated using FTIR spectroscopy. The results indicate that the SAIL was soluble in the aqueous DES solutions and forms self-assembled structures. Furthermore, Dynamic Light Scattering (DLS) measurements were performed to determine the aggregate size of SAIL in aqueous DES media.
