Synthesis and Molecular Docking Study of a Novel 4-Hydroxycoumarin-Based Warfarin Analogue

Warfarin analogue compounds were synthesized from 4-hydroxycoumarin and 3-phenyl-1-(thiophen-2-yl)prop-2-en-1-one in an alkaline medium via  Michael addition reaction. Initially, both 4-hydroxycoumarin and the chalcone derivative (3-phenyl-1-(thiophen-2-yl)prop-2-en-1-one) were synthesized, with 4-hydroxycoumarin obtained in satisfactory yield. The heterocyclic chalcone was prepared at room temperature under alkaline conditions using a simple Claisen–Schmidt (crossed aldol) condensation method. Subsequently, 4-hydroxycoumarin was reacted with the synthesized chalcones to afford the target novel compounds through Michael addition. The structures of the synthesized compounds were confirmed by FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry analyses. Molecular docking studies of the novel warfarin analogue using AutoDock Vina revealed a high binding affinity (−10.9 kcal/mol) toward AKT1 kinase. The presence of multiple hydrogen bonding, electrostatic, and hydrophobic interactions with key catalytic residues suggests strong potential for AKT1 inhibitory activity.