Background:
Diabetes mellitus is one the most chronic metabolic disorder. Since past few years our research
group had synthesized and evaluated libraries of heterocyclic compounds against α and β-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 α and βglucosidase 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 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated
for α and β-glucosidase inhibitions by adopting the literature protocols.
Result:
Off twenty three, eleven compounds displayed good to moderate activity against α-glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against β-glucosidase enzyme. Compounds 1, 14, and 23 displayed
good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 µM, respectively.
The results have shown that these compounds have selectively inhibited the α-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 α-glucosidase and may potentially serve as
lead for the development of new therapeutic representatives.