Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

A library of novel bis -Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after struct...

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Bibliographic Details
Published in:Scientific reports Vol. 14; no. 1; pp. 3419 - 14
Main Authors: Gul, Saba, Jan, Faheem, Alam, Aftab, Shakoor, Abdul, Khan, Ajmal, AlAsmari, Abdullah F., Alasmari, Fawaz, Khan, Momin, Bo, Li
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 10.02.2024
Nature Publishing Group
Nature Portfolio
Subjects:
631/114
631/154
631/45
639/638
Acarbose
Acids
bis-Schiff bases
Carbohydrates
Carbon
Chemistry
DFT
Diabetes
Diabetes mellitus
Drugs
Enzymes
Ethanol
Humanities and Social Sciences
Hyperglycemia
Libraries
Materials science
Molecular docking
multidisciplinary
NMR spectroscopy
Protons
Science
Science (multidisciplinary)
Solvents
Thiobarbituric acid
α-Glucosidase
α-Glucosidase inhibition
Schiff bases
α-Glucosidase inhibition
DFT
Thiobarbituric acid
NMR spectroscopy
Molecular docking
bis-Schiff bases
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:A library of novel bis -Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC 50  = 0.10 ± 0.05 µM), and 9 (IC 50  = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC 50  = 0.27 ± 0.04 µM). Similarly, derivatives ( 5 , 6 , 7 , 10 and 4 ) showed significant to good inhibitory activity in the range of IC 50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-54021-z