Synthesis of Some Novel Pyrrolidine-Based Iminosugars, Molecular Docking Study and Evaluation of Their Antidiabetic Properties

Eleven pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of a-glucosidase and molecular docking. The compounds studied were hydrazinyl, hydroxyamino and hydroxypyrrolidine derivatives. The most promising iminosugar derivative was 3-hydrazinyl-4-hydroxymethyl-1-methyl-5-(4-methoxyphneyl) pyrrolidine (CoS-10), giving an IC50 of 1.116 ± 1.01 mM. The hydrazine group at C-4 and methoxybenzene ring at C-2 seemed to play important roles in the activity of CoS-10. Docking studies showed that all the compounds occupied the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Despite the fact that activity was found only in the mM range, this study demonstrated that the newly synthesized compounds had promising effects in inhibiting α-glucosidase, so that inhibition can be improved in further studies.