Exploration of newly synthesized azo-thiohydantoins as the potential alkaline phosphatase inhibitors via advanced biochemical characterization and molecular modeling approaches.

In the current study, Azo-Thiohydantoins derivatives were synthesized and characterized by using various spectroscopic techniques including FTIR, H-NMR, C-NMR, elemental and HRMS analysis. The compounds were evaluated for alkaline phosphatase activity and it was observed that among all the synthesized compounds, derivative 7e exhibited substantial inhibitory activity (IC = 0.308 ± 0.065 µM), surpassing the standard inhibitor (L-Phenyl alanine, IC = 80.2 ± 1.1 µM). Along with this, these derivatives were comprehensively examined regarding the electronic properties and reactivity of the synthesized compounds using Density Functional Theory (DFT) calculations, where the results were found very promising and the synthesized compound were found stable. After that, SwissADME evaluations highlighted compounds for their favorable physicochemical properties, including solubility and drug-likeness. Molecular docking exhibited the strong binding affinities of 7f and 7e derivatives with intestinal alkaline phosphatase (IAP), further supported by Molecular Dynamics (MD) simulations. This comprehensive integration of experimental and computational approaches sheds the light on the potential therapeutic applications of the synthesized compounds. By providing a detailed investigation of these aspects, this research opens the avenues for the development of novel pharmacologically active compounds with diverse applications.