Development of Oxazine‐Based Hybrids as Inhibitors of <i>α</i> ‐Amylase, <i>α</i> ‐Glucosidase, Acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE) Enzymes, and Potential Therapeutics for Diabetes, Alzheimer's Disease, and Oxidative Stress

ABSTRACT Oxazin‐4‐one‐based synthetic derivatives ( 1–30 ) were evaluated for inhibitory activity against α ‐amylase, α ‐glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The molecules demonstrated potent inhibition, with IC 50 values of 18.65 ± 0.23 µ M to 37.70 ± 0.06 µ M for α ‐amylase and 15.68 ± 0.36 to 37.47 ± 0.13 µ M for α ‐glucosidase, comparable to the reference drug acarbose (IC 50 = 16.98 ± 0.12 µ M and 14.19 ± 0.06 µ M, respectively). Antioxidant capacity was quantified using DPPH and ABTS radical scavenging assays. Kinetic analysis identified competitive and mixed‐type inhibition mechanisms, while molecular docking simulations characterized the binding interactions within the active sites. Overall, these findings suggest that oxazin‐4‐one derivatives may serve as promising multitarget starting points for further optimization toward metabolic, neurodegenerative, and oxidative‐stress‐related pathways.

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Publication Details

Journal
ChemistrySelect
Published
2026-07-27
DOI
https://doi.org/10.1002/slct.73911
Primary Topic
Enzyme function and inhibition
Type
article
Field-Weighted Citation Impact
0.00

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article

Development of Oxazine‐Based Hybrids as Inhibitors of α ‐Amylase, α ‐Glucosidase, Acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE) Enzymes, and Potential Therapeutics for Diabetes, Alzheimer's Disease, and Oxidative Stress

Uzma Salar, Muhammad Taha, Vasudevan Mani, Nisar Ullah et al.
ChemistrySelect
Enzyme function and inhibition
article

Development of Oxazine‐Based Hybrids as Inhibitors of α ‐Amylase, α ‐Glucosidase, Acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE) Enzymes, and Potential Therapeutics for Diabetes, Alzheimer's Disease, and Oxidative Stress

Uzma Salar, Muhammad Taha, Vasudevan Mani, Nisar Ullah, Sridevi Chigurupati, Yousaf Khan, Mehwish Solangi, Khan Ka, Supriya Srivatsava, Zaheer Ul‐Haq, Shamoon Tariq
article en

Abstract

ABSTRACT Oxazin‐4‐one‐based synthetic derivatives ( 1–30 ) were evaluated for inhibitory activity against α ‐amylase, α ‐glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The molecules demonstrated potent inhibition, with IC 50 values of 18.65 ± 0.23 µ M to 37.70 ± 0.06 µ M for α ‐amylase and 15.68 ± 0.36 to 37.47 ± 0.13 µ M for α ‐glucosidase, comparable to the reference drug acarbose (IC 50 = 16.98 ± 0.12 µ M and 14.19 ± 0.06 µ M, respectively). Antioxidant capacity was quantified using DPPH and ABTS radical scavenging assays. Kinetic analysis identified competitive and mixed‐type inhibition mechanisms, while molecular docking simulations characterized the binding interactions within the active sites. Overall, these findings suggest that oxazin‐4‐one derivatives may serve as promising multitarget starting points for further optimization toward metabolic, neurodegenerative, and oxidative‐stress‐related pathways.

ChemistrySelectVol. 11(29)
King Fahd University of Petroleum and Minerals (SA), Qassim University (SA), University of Karachi (PK), Pakistan Academy of Sciences (PK), Buraydah Colleges (SA), International Center for Chemical and Biological Sciences (PK), Imam Abdulrahman Bin Faisal University (SA)
Pakistan Academy of Sciences
Openalex Percentile: Top 15%
Enzyme function and inhibition
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