Phenoxy pendant isatins as potent α-glucosidase inhibitors: reciprocal carbonyl•••carbonyl interactions, antiparallel π•••π stacking driven solid state self-assembly and biological evaluation

Carbonyl-carbonyl (CO center dot center dot center dot CO) interactions are recently explored noncovalent interactions of significant interest owing to their role in the stability of biomacromolecules. Currently, substantial efforts are being made to understand the nature of these interactions. In this study, twelve phenoxy pendant isatins 1-12 have been evaluated for their alpha-glucosidase inhibitory potential in addition to the analysis of X-ray single crystals of 4 and 9. Both compounds 4 and 9 showed intriguing and unique self-assembled structures. The CO center dot center dot center dot CO and antiparallel displaced pi center dot center dot center dot pi stacking interactions are mainly involved in the formation of 1D-stair like supramolecular chains of 4 whereas antiparallel pi center dot center dot center dot pi stacking interactions drive the formation of 1D-columnar stacks of 9. These compounds not only highlight the potential of the isatin moiety in forming strong CO center dot center dot center dot CO and antiparallel pi center dot center dot center dot pi stacking interactions but also are interesting models to provide considerable insight into the nature of these interactions. The in vitro biological studies revealed that all twelve phenoxy pendant isatins 1-12 are highly potent inhibitors of alpha-glucosidase enzyme with IC50 values ranging from 5.32 +/- 0.17 to 150.13 +/- 0.62 mu M, showing many fold more potent activity than the standard drug, acarbose (IC50 = 873.34 +/- 1.67). Easy access and high alpha-glucosidase inhibition potential of these phenoxy pendant isatins 1-12 provide an attractive platform for finding more effective medication for controlling postprandial hyperglycemia.