Synthesis, characterization, comparative study, DFT analysis, ADMET prediction and molecular docking study of Thiophen-2-yl and 4-pyridinyl derivatives of bis (4-hydroxy-2H-chromen-2-one)

The primary objective of this research was to design and synthesize novel bis(4-hydroxy-2H-chromen-2-one) derivatives bearing thiophen-2-yl and 4-pyridinyl substituents with potential anti-inflammatory properties, utilizing an environmentally friendly and economically viable synthetic approach. To achieve this, 4-hydroxycoumarin was condensed with thiophene-2-aldehyde and pyridine-4-carboxaldehyde using Amberlite 400 Cl − resin, an effective and reusable heterogeneous catalyst. The resulting compounds were structurally optimized and characterized using Density Functional Theory (DFT) at the B3LYP/6–311 + G(d,p) level, which also enabled theoretical predictions of their UV–Visible spectra and vibrational modes. Computational analysis was performed to identify the potential biological targets of this set of compounds using Swiss ADME, a cutting-edge computational tool that, in place of tests, allows for the examination and prediction of a wide range of physicochemical characteristics, drug-likeness, pharmacokinetics, and medicinal chemistry. Further, ADMET predictions were performed to estimate absorption, distribution, metabolism, excretion, and toxicity characteristics. Additionally, molecular docking simulations were performed using the titled compounds as ligands against various anti-inflammatory target proteins, with AutoDock Vina, and the results were visualized in Discovery Studio. A comprehensive theoretical and computational investigation, encompassing DFT, ADMET, SwissADME, and molecular docking, highlighted the pharmacological relevance of the synthesized compounds. These findings suggest that the titled compounds could serve as promising NLO materials, prominent candidates for the development of new anti-inflammatory agents, which further leave a scope for biological evaluation and in vitro/in vivo studies.