JOURNAL OF PHARMACOLOGY AND
BIOMEDICINE
ISSN.2456-8244
The present study aimed to synthesize, characterize, and evaluate the anticholinesterase potential of novel 1,8- naphthyridine derivatives along with their physicochemical and pharmacokinetic properties. A series of five compounds, namely 4-methyl-1,8-naphthyridine-2,6-diyl dibenzoate derivatives (ANB1-5), were synthesized through a multistep synthetic pathway involving the formation of 2,6-dihydroxy-4-methyl-1,8-naphthyridine followed by esterification with substituted benzoyl chlorides. Anticholinesterase activity was determined using Ellman's colorimetric method, while drug-likeness and ADMET properties were predicted using SwissADME and pkCSM online tools. The synthesized derivatives exhibited moderate to good yields (67-71%) and demonstrated dose- dependent inhibition of acetylcholinesterase enzyme. Among the tested compounds, ANB3 exhibited the highest anticholinesterase activity with 65.07% inhibition at 10 mM concentration and the lowest IC₅₀ value (6.89 mM), indicating superior potency compared to the other derivatives. In silico studies revealed favorable pharmacokinetic profiles with excellent intestinal absorption (>95%), compliance with Lipinski's rule of five, and acceptable drug- likeness characteristics. The ADMET analysis suggested that ANB3 possessed the most balanced profile in terms of absorption, lipophilicity, and biological activity. Overall, the findings identify ANB3 as a promising lead candidate for further optimization and development as a potential anticholinesterase agent for the management of neurodegenerative disorders.
NAMES:
ONLINE ISSN:24568244
Keywords: 1,8-napthyridine, anti-cholinesterase, Ellman’s method, in-silico, Alzheimer’s disease
DOI:
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