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.
Authors
- Uzma Salar (ORCID: https://orcid.org/0000-0003-1871-9112)
- Muhammad Taha (ORCID: https://orcid.org/0000-0003-3047-9289)
- Vasudevan Mani (ORCID: https://orcid.org/0000-0002-8440-8366)
- Nisar Ullah (ORCID: https://orcid.org/0000-0002-8172-2771)
- Sridevi Chigurupati (ORCID: https://orcid.org/0000-0002-1081-2964)
- Yousaf Khan (ORCID: https://orcid.org/0000-0001-5455-7849)
- Mehwish Solangi (ORCID: https://orcid.org/0000-0003-1082-9499)
- Khan Ka
- Supriya Srivatsava
- Zaheer Ul‐Haq (ORCID: https://orcid.org/0000-0002-8530-8711)
- Shamoon Tariq (ORCID: https://orcid.org/0000-0001-5692-8703)
Institutions
- 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)
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
Funders
- Pakistan Academy of Sciences