Skeletal rearrangement in Biginelli reaction for the synthesis of chromenoquinoline fused spirohydantoins and their in silico cytotoxicity study.

Although Biginelli reaction is known to generate dihydropyrimidinones having wide arrays of phramacological properties, herein we report an unprecedented skeletal rearrangement in Biginelli reaction to synthesize pharmacologically versatile imidazolidine-2,4-diones, popularly known as hydantoins. Here a mixture of isatin, 4-hydroxycoumarin and 1,3-dimethylurea reacts in the presence of a catalytic amount of p-TsOH to generate spirohydantoins fused with chromenoquinoline moiety. Skeletal rearrangement of the 5-membered keto-lactam ring of isatin to a structurally constrained 5-membered ring in the form of spirohydantoins is the most interesting feature of this protocol. Nonetheless, the reaction introduces a novel molecular architecture bearing medicinally important spirohydantoin and chromenoquinoline scaffolds. In-silico molecular docking simulation of the synthesized compounds against human kinesin Eg5 (PDB ID: 2IEH) along with 17 other tumor-associated targets demonstrated strong binding efficiency, indicating that these compounds merit further biological evaluation to validate their anticancer potential.