Synthesis and Biological Evaluation of Coumarin Derivatives Targeting Oxidative Stress in Neurodegenerative Diseases
Year: 2026
Type: article
Abstract: Neurodegenerative disorders, particularly Alzheimer’s disease, are closely associated with oxidative stress, cholinergic dysfunction, and progressive neuronal damage. In the present study, a series of coumarin derivatives (C1–C6) was designed, synthesized, and evaluated for their antioxidant and acetylcholinesterase inhibitory potential with the aim of identifying multifunctional lead compounds for neurodegenerative disorders. The coumarin scaffold was selected because of its well-established pharmacological versatility and its ability to accommodate structural modifications that may enhance biological activity. The synthesized derivatives were characterized by physicochemical analysis and Fourier-transform infrared spectroscopy, which confirmed the presence of characteristic functional groups such as hydroxyl, lactone carbonyl, aromatic C=C, and C–O moieties. Antioxidant activity was assessed using DPPH, ABTS, and ferric-reducing antioxidant power assays, while acetylcholinesterase inhibition was evaluated as a neurodegeneration-relevant target-based parameter. The results demonstrated that all compounds exhibited varying degrees of antioxidant and enzyme inhibitory activity depending on the nature of the substituents present on the coumarin nucleus. Among the tested derivatives, compound C4 showed the most promising overall biological profile, with comparatively lower IC₅₀ values in the DPPH and ABTS assays, higher ferric-reducing potential, and the strongest acetylcholinesterase inhibitory activity among the synthesized compounds. Structure–activity relationship analysis suggested that hydroxyl substitution significantly enhanced antioxidant activity, while appropriate electronic and steric features also contributed to enzyme inhibition. Overall, the findings indicate that rational modification of the coumarin scaffold can generate multifunctional derivatives with potential relevance in the management of oxidative stress-mediated neurodegenerative disorders. These results support further studies involving molecular docking, ADMET profiling, cellular models, and in vivo neuroprotective evaluation of the lead compound.
Source: Oriental Journal Of Chemistry
DOI: 10.13005/ojc/420535
Institutions: Noida Institute of Engineering and Technology Pharmacy Institute, Noida Institute of Engineering and Technology, Saveetha University, Nightingales Medical Trust, Teerthanker Mahaveer University, Shri Vidyarthi Sudhar Sangh’s Nagpur College of Pharmacy, Sri Balaji Vidyapeeth University, Vels University
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7225124339