Targeting Cholinergic, MAO, and Amyloid‐β Pathways: Spectroscopic, DFT, and In Silico Evaluation of Ethyl 5‐Chloroindole‐2‐Carboxylate for Alzheimer's Disease

ABSTRACT

Alzheimer's disease (AD) is a long‐term brain disorder that causes gradual memory loss and cognitive decline. In this study, ethyl 5‐chloroindole‐2‐carboxylate (ECIC) was studied using both experimental and computational methods. The molecular structure and vibrations were analyzed using DFT/B3LYP/6‐311++G(d,p), and the results were in good agreement with the FT‐IR, FT‐Raman, and UV–vis spectra. TD‐DFT calculations gave information about electronic properties, including the HOMO–LUMO energy gap (4.47 eV) and reactivity. Advanced topological analysis, including ELF, LOL, and RDG, was performed to examine the compound's electron density distribution. ADMET prediction showed that ECIC has good pharmacokinetic properties and safe characteristics. Docking studies showed that ECIC binds to 4EY7 (−8.1 kcal mol ⁻¹ ), 1GOS (−8.0 kcal mol ⁻¹ ), and 2BEG (−6.1 kcal mol ⁻¹ ), with binding affinities comparable to those of the standard drug, indicating good interactions with Alzheimer's‐related proteins. In vitro antioxidant activity by DPPH assay showed an IC ₅₀ value of 34.54 µg mL ⁻¹ for ECIC. The ferric reducing power assay demonstrated ECIC's concentration‐dependent reducing ability. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities showed IC ₅₀ values of 40.68 and 35.89 µg mL ⁻¹ , respectively. Overall, the combined experimental and computational results suggest that ECIC has potential as a candidate for Alzheimer's disease and support further experimental investigation.