IN SILICO IDENTIFICATION OF BIOACTIVE COMPOUNDS FROM MEDICINAL PLANTS AS POTENTIAL GLUCOKINASE INHIBITORS FOR DIABETES MANAGEMENT
Keywords:
Diabetes, Target-protein, Glucokinase, In silico studies, Molecular docking, PhytochemicalsAbstract
Diabetes, a chronic elevation in blood glucose levels, is primarily caused by the inactivation of glucoki-
nase, a glucose sensor enzyme present in insulin-secreting pancreatic beta cells. This study investi-
gated the inhibitory potential and proposed competitive binding mechanism of bioactive compounds
from six medicinal plants: (Mormordica charantia L., Aloe barbadensis Mill., Cinnamomum zeylanicum
L., Vernonia amygdalina H., Persea americana M., and Trigonella foenum-graecum L.) against Gluco-
kinase active sites. Thirty (30) bioactive compounds were selected and screened together with Pi-
ragliatin (control drug). The PubChem identification number, 3D structure, and canonical SMILES of
the phytocompounds and control drug were obtained using the PubChem online server. Drug likeness
screening and other molecular docking analyses were carried out using web-based tools
(SwissADME, AutoDock Vina, and Molinspiration). The absorption, distribution, metabolism, excretion
(ADMET), and toxicity profiles of the ligands were evaluated using ADMETlab online tool. The drug-
likeness screening showed that 23 of 30 bioactive compounds violated one or more of the four rules
(Lipinski, Ghose, Veber, and Egan). The protein-ligand docking revealed that anthraquinone, cin-
namaldehyde, coumarin, beta-amyrin, diosgenin, lutein, zeaxanthin, beta-carotene, and silymarin had
higher binding energies of -8.8 kcal/mol, -7.6 kcal/mol, -8.1 kcal/mol, -7.8 kcal/mol, -8.6 kcal/mol, -7.8
kcal/mol, -7.8 kcal/mol, -8.5 kcal/mol, -7.5 kcal/mol, respectively compared with that of Piragliatin (-7.0
kcal/mol). Compounds with higher binding affinity violated at least one rule except for the non-
carcinogenic anthraquinone with no drug-likeness screening violation. This study revealed anthraqui-
none and other lead bioactive compounds as potential antidiabetic drugs for further consideration and
wet lab experimentation.
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