Identification α-Amylase Inhibitors of  Vernonia amygdalina  Leaves Extract Using Metabolite Profiling Combined with Molecular Docking

Norainny Yunitasari; Tri Joko Raharjo; Respati Tri Swasono; Harno Dwi Pranowo

doi:10.22146/ijc.71499

Identification α-Amylase Inhibitors of Vernonia amygdalina Leaves Extract Using Metabolite Profiling Combined with Molecular Docking

https://doi.org/10.22146/ijc.71499

Norainny Yunitasari^(1*), Tri Joko Raharjo⁽²⁾, Respati Tri Swasono⁽³⁾, Harno Dwi Pranowo⁽⁴⁾

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, PO BOX BLS 21, Yogyakarta 55281, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, PO BOX BLS 21, Yogyakarta 55281, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, PO BOX BLS 21, Yogyakarta 55281, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, PO BOX BLS 21, Yogyakarta 55281, Indonesia
(*) Corresponding Author

Abstract

Vernonia amygdalina was reported to be used as a therapy for Diabetes Mellitus (DM). One of the mechanisms of therapy DM was to inhibit the action of the α-amylase enzyme. This study aimed to prove the presence of compounds that could inhibit the action of α-amylase. Vernonia amygdalina leaves were macerated with methanol and partitioned into n-hexane, dichloromethane (DCM), and ethyl acetate (EtOAc). Furthermore, they were tested for α-amylase inhibitory activity and analyzed using liquid chromatography-high resolutions mass spectrometry (LC-HRMS). Molecular docking and molecular dynamics simulation (MD simulation) examined unique compounds in the extract with good activity and chromatogram results. The EtOAc extracts showed potential as α-amylase inhibitors indicated by their IC₅₀ values, namely 3.0 μg/mL. There are five unique compounds in the EtOAc extract predicted as 3-[(2Z)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-(2-phenylethyl)benzoic acid (compound 1), 2-hexylpentanedioic acid (compound 2), (2E,4E)-5-[1-hydroxy-2,6-dimethyl-4-oxo-6-({3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] oxy}methyl)cyclohex-2-en-1-yl]-3-methylpenta-2,4-dienoic acid (compound 3), 3,5,5-trimethyl-4-(3-{[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-1-yl)oxy}butyl)cyclohex-2-en-1-one (compound 4), and 2-{[(6E)-2,10-dihydroxy-2,6,10-trimethyldodeca-6,11-dien-3-yl]oxy}-6-(hydroxymethyl)oxane-3, 4,5-triol (compound 5). The molecular docking analysis showed that compound 3 had better interaction energy (E_i) (-8.59 kcal/mol) and inhibition constant (Ki) values (0.503 μM) than acarbose. These data were supported by MD simulations based on the parameters of RMSD value, the radius of gyration, and protein-ligand interaction energy.

Keywords

ethyl acetate extract; diabetes mellitus; LC-HRMS; protein 4GQR; molecular dynamic simulation

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DOI: https://doi.org/10.22146/ijc.71499