Indane-1,3-diones: As Potential and Selective α-glucosidase Inhibitors, their Synthesis, in vitro and in silico Studies

Background: Diabetes mellitus is one of the most chronic metabolic disorders. Since past few years, our research group had synthesized and evaluated libraries of heterocyclic compounds against alpha and beta-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. Objective: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for alpha and beta-glucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. Method: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques, including H-1-, C-13-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for alpha and beta-glucosidase inhibitions by adopting the literature protocols. Result: Off twenty three, eleven compounds displayed good to moderate activity against alpha-glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against beta-glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against alpha-glucosidase enzyme with IC50 values of 2.80 +/- 0.11, 0.76 +/- 0.01, and 2.17 +/- 0.18 mu M, respectively. The results have shown that these compounds have selectively inhibited the alpha-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. Conclusion: The compounds 1, 14, and 23 have shown good inhibition against alpha-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.