In silico ADMET Study, Synthesis and Anticholinesterase Activity of 1,8-Naphthyridine Derivatives

Abstract

Background: This study aimed to synthesize 1,8-naphthyridine derivatives, conduct an in silico ADMET analysis, and evaluate the compounds' anti-cholinesterase activity in vitro. Materials and Methods: The Conrad-Limpach method employed ethylacetoacetate and 2-aminopyridine to synthesize 1,8-naphthyridine derivatives. A modified Ellman's methodology was employed to assess the anti-cholinesterase activity of our synthesized compounds and to determine the percent inhibition and IC50 values. Results: The compounds exhibit a yield ranging from 65% to 72%. All compounds satisfy Lipinski's five criteria; hence, they adhere to the rule. Conclusion: The synthesized compounds inhibited AChE activity in a dose-dependent manner, ranging from 3.54% to 64.06%. The IC50 values, derived from the inhibition percentage, were determined to be 9.99 µM, 10.87 µM, 7.64 µM, 17.01 µM, and 12.74 µM for HSN1 through HSN5, respectively. The suppression of cholinesterase enzyme obstructs the degradation of acetylcholine into its constituents, choline and acetyl-CoA. The chemicals inhibited the cholinesterase enzyme in a dose-dependent manner. The findings prompted us to determine that 1,8-naphthyridine derivatives may be refined to yield prospective AChE inhibitors.