Drug screening of α‐amylase inhibitors as candidates for treating diabetes

In the present study, the identification of potential α‐amylase inhibitors is explored as a potential strategy for treating type‐2 diabetes mellitus. A computationally driven approach using molecular docking was employed to search for new α‐amylase inhibitors. The interactions of potential drugs wit...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2023-08, Vol.27 (15), p.2249-2260
Main Authors: Alp, Meryem, Misturini, Alechania, Sastre, German, Gálvez‐Llompart, Maria
Format: Article
Language:English
Subjects:
Acarbose
Acarbose - chemistry
Acarbose - pharmacology
Acarbose - therapeutic use
alpha-Amylases
Antidiabetics
Binding sites
Candidates
database screening
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - metabolism
docking
Drug Evaluation, Preclinical
Drug interaction
Drug screening
Drugs
Enzymes
Glucose
Glycoside Hydrolase Inhibitors - chemistry
Glycoside Hydrolase Inhibitors - metabolism
Glycoside Hydrolase Inhibitors - pharmacology
Humans
Hyperglycemia
Insulin resistance
Lethal dose
Ligands
Metabolism
Molecular Docking Simulation
molecular dynamics
Original
protein binding
Proteins
Simulation
Toxicity
type‐2 diabetes
α-Amylase
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Summary:In the present study, the identification of potential α‐amylase inhibitors is explored as a potential strategy for treating type‐2 diabetes mellitus. A computationally driven approach using molecular docking was employed to search for new α‐amylase inhibitors. The interactions of potential drugs with the enzyme's active site were investigated and compared with the contacts established by acarbose (a reference drug for α‐amylase inhibition) in the crystallographic structure 1B2Y. For this active site characterization, both molecular docking and molecular dynamics simulations were performed, and the residues involved in the α‐amylase–acarbose complex were considered to analyse the potential drug's interaction with the enzyme. Two potential α‐amylase inhibitors (AN‐153I105594 and AN‐153I104845) have been selected following this computational strategy. Both compounds established a large number of interactions with key binding site α‐amylase amino acids and obtained a comparable docking score concerning the reference drug (acarbose). Aiming to further analyse candidates' properties, their ADME (absorption, distribution, metabolism, excretion) parameters, druglikeness, organ toxicity, toxicological endpoints and median lethal dose (LD50) were estimated. Overall estimations are promising for both candidates, and in silico toxicity predictions suggest that a low toxicity should be expected.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.17831