Synthesis, structural characterization, and molecular docking study of new phthalhydrazide-coumarin hybrids

Abstract A series of new phthalhydrazide-coumarin hybrids was obtained in the reaction of phthalhydrazide with corresponding bromopropoxycoumarin derivatives. These reactions were performed in the presence of Cs2CO3, in acetonitrile as solvent, and under reflux for 5 h. Obtained hybrids contain one or two coumarin scaffolds bonded to phthalhydrazide nitrogen via propoxy linker. Ten new phthalhydrazide-coumarin hybrids were obtained in moderate to good yields, and characterized with melting point, elemental analysis, IR and NMR spectroscopy, and LC-MS spectrometry. Additionally, the structures of these compounds were elucidated based on experimental and theoretical data (IR, 1H NMR, and 13C NMR). Excellent agreement between experimental and simulated spectra was achieved. The prediction of the potential biological activity of synthesized compounds was done using the online program PASS (Prediction of Activity Spectra for Substances). Based on the obtained results, the serotonin 2A receptor (5-HT2AR) was selected for molecular docking study. Molecular docking was also performed with commercially available drug Risperidone, and obtained results were compared with potential bioactive conformations of obtained phthalhydrazide-coumarin hybrids.