Design, synthesis and biological evaluation of small molecules as potent glucosidase inhibitors

• We designed and synthesized a molecular library.
• In vitro screening identified two compounds as potent α-glucosidase inhibitors.
• Reaction kinetics suggested mixed type inhibition.
• Phenotypic screening of one of the compounds also indicated antimalarial properties.

Herein we have reported design, synthesis and in vitro biological evaluation of a library of bicyclic lactams that led to the discovery of compounds 6 and 7 as a novel class of α-glucosidase inhibitors. They inhibited α−glucosidase (yeast origin) in a mixed type of inhibition with an IC50 of ∼150 nM. Molecular docking studies further substantiated screening results. Interestingly phenotypic screening of this library against the human malaria parasite revealed 7 as a potent antiplasmodial agent.

A bicyclic lactam has been discovered as a novel mixed inhibitor of α-glucosidase (yeast) enzyme that also inhibits 3D-7 strain of Plasmodium Falciparum.Figure optionsDownload as PowerPoint slide