Insights into the Inhibition Mechanism of Human Pancreatic α-Amylase, a Type 2 Diabetes Target, by Dehydrodieugenol B Isolated from Ocimum tenuiflorum

Prasad D Dandekar; Amol S Kotmale; Shrawan R Chavan; Pranita P Kadlag; Sangeeta V Sawant; Dilip D Dhavale; Ameeta RaviKumar

doi:10.1021/acsomega.0c00617

Insights into the Inhibition Mechanism of Human Pancreatic α-Amylase, a Type 2 Diabetes Target, by Dehydrodieugenol B Isolated from Ocimum tenuiflorum

ACS Omega. 2021 Jan 13;6(3):1780-1786. doi: 10.1021/acsomega.0c00617. eCollection 2021 Jan 26.

Authors

Prasad D Dandekar¹, Amol S Kotmale¹, Shrawan R Chavan¹, Pranita P Kadlag¹, Sangeeta V Sawant¹, Dilip D Dhavale¹, Ameeta RaviKumar¹

Affiliation

¹ Institute of Bioinformatics and Biotechnology, Garware Research Centre, Department of Chemistry, and Bioinformatics Centre, Savitribai Phule Pune University (Formerly University of Pune), Pune 411007 Maharashtra, India.

Abstract

Use of human pancreatic α-amylase (HPA) inhibitors is one of the effective antidiabetic strategies to lower postprandial hyperglycemia via reduction in the dietary starch hydrolysis rate. Many natural products from plants are being studied for their HPA inhibitory activity. The present study describes isolation of dehydrodieugenol B (DDEB) from Ocimum tenuiflorum leaves using sequential solvent extraction, structure determination by one-dimensional (1D) and two-dimensional (2D) NMR analyses, and characterization as an HPA inhibitor using kinetics, binding thermodynamics, and molecular docking. DDEB uncompetitively inhibited HPA with an IC₅₀ value of 29.6 μM for starch and apparent K _i ' of 2.49 and K_i of 47.6 μM for starch and maltopentaose as substrates, respectively. The circular dichroism (CD) study indicated structural changes in HPA on inhibitor binding. Isothermal titration calorimetry (ITC) revealed thermodynamically favorable binding (ΔG of -7.79 kcal mol^-1) with a dissociation constant (K _d) of 1.97 μM and calculated association constant (K _a) of 0.507 μM. Molecular docking showed stable HPA-inhibitor binding involving H-bonds and Pi-alkyl, alkyl-alkyl, and van der Waals (vDW) interactions. The computational docking results support the noncompetitive nature of DDEB binding. The present study could be helpful for exploration of the molecule as a potential antidiabetic drug candidate to control postprandial hyperglycemia.