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

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

Volume: 17 Issue: 8

Author(s): Asma Mukhtar, Shazia Shah, Kanwal, Shehryar Hameed, Khalid Mohammed Khan*, Shahid Ullah Khan, Sumera Zaib, Jamshed Iqbal*Shahnaz Perveen

Affiliation:

• H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270,Pakistan

• Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad-22060,Pakistan

Keywords: Indane-1, 3-dione, α-glucosidase, in silico study, β-glucosidase, diabetes mellitus, synthesis.

Abstract:

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 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 β-glucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme.

Methods: 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.

Cite this article as:

Mukhtar Asma , Shah Shazia, Kanwal , Hameed Shehryar , Khan Mohammed Khalid*, Khan Ullah Shahid , Zaib Sumera, Iqbal Jamshed*, Perveen Shahnaz , Indane-1,3-diones: As Potential and Selective α-glucosidase Inhibitors, their Synthesis, in vitro and in silico Studies, Medicinal Chemistry 2021; 17 (8) . https://dx.doi.org/10.2174/1573406416666200826102051