In silico exploration of Isoxazole derivatives of usnic acid: novel therapeutic prospects against α-Amylase for diabetes treatment

Roney, Miah and Issahaku, Abdul Rashid and Huq, A. K. M. Moyeenul and Suhaila, Sapari and Fazira Ilyana, Abdul Razak and Wilhelm, Anke and Normaiza, Zamri and Sharmin, Sabrina and Islam, Md. Robiul and Mohd Fadhlizil Fasihi, Mohd Aluwi (2024) In silico exploration of Isoxazole derivatives of usnic acid: novel therapeutic prospects against α-Amylase for diabetes treatment. Cell Biochemistry and Biophysics. pp. 1-17. ISSN 1085-9195. (In Press / Online First) (In Press / Online First)

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DOI/Official URL: https://doi.org/10.1007/s12013-024-01419-1

Abstract

Diabetes mellitus (DM) a metabolic disorder characterized by high blood sugar levels causing damage to various organs over time. Current anti-diabetic drugs have limitations and side effects, prompting a search for new inhibitors targeting the α-amylase enzyme. This study aims to discover such inhibitors from thirty isoxazole derivatives of usnic acid using in silico approaches. The potential inhibitory effects of compounds were investigated using ADMET, molecular docking, molecular dynamic simulation, principal component analysis and density functional theory studies. ADMET analysis exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities with no significant side effects which were then investigated using molecular docking experiment to determine the lead compound with the best binding affinity for the α-amylase enzyme. All compounds showed good binding affinity against α-amylase enzyme (−7.9 to −9.2 kcal/mol) where compound-13 showed the best binding affinity of −9.2 kcal/mol forming hydrogen bonds with Leu162, Tyr62, Glu233 and Asp300 amino acids. Furthermore, the binding posture and the stability of the compound-13-α-amylase enzyme complex was confirmed by molecular dynamic simulation experiment. Moreover, compound-13 showed binding energy value of −27.92 ± 5.61 kcal/mol, which indicated it could be an α-amylase inhibitor. Additionally, the reactivity of compound-13 was further confirmed by density functional theory analysis. The above findings suggest compound-13 to be a potential α-amylase inhibitor in DM. And setting the stage for further in vitro and in vivo experimental validation.

Item Type:	Article
Additional Information:	Indexed by Scopus
Uncontrolled Keywords:	Anti-diabetic; DFT; docking; MD Simulation; α-amylase
Subjects:	H Social Sciences > HD Industries. Land use. Labor R Medicine > R Medicine (General)
Faculty/Division:	Faculty of Industrial Sciences And Technology Institute of Postgraduate Studies Centre for Bioaromatic Research (Bioaromatic Centre)
Depositing User:	Miss Amelia Binti Hasan
Date Deposited:	16 Aug 2024 04:04
Last Modified:	16 Aug 2024 04:06
URI:	http://umpir.ump.edu.my/id/eprint/42377
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