Abstract
Computer-aided drug design (CADD) plays a key role in modern drug discovery. In the present in silico study, two sets of compounds were developed computationally considering the structures of juarezic acid and avenalumic acid. In the first set (compounds 1 – 8), the carboxylic acid group was replaced by ester, amide or nitrile. In the second set (compounds 9 – 16), α-nitrile substituent was introduced and verified its effect on molecular properties especially log P, hydrogen bond acceptor and TPSA as well as druglikeness, pharmacokinetics, bioactivity score and toxicity using Molinspiration Cheminformatics, SwissADME and OSIRIS Property Explorer. All the compounds were evaluated in silico and were found to obey Lipnski’s rule confirming their druglikeness and pharmacokinetic properties. Among all, avenalumic acid, avenalumamide, α-cyanoavenalumic acid and juarezic acid (compounds 5, 7, 13 and 1) were estimated as active enzyme inhibitors. Additionally, α-cyanoavenalumic acid 13 was estimated as an active nuclear receptor ligand. These observations indicate the essential structural requirements like phenolic hydroxyl group, a diene system conjugating with carboxylic acid or amide and α-nitrile substitution for the bioactivity as enzyme inhibitor and nuclear receptor ligand. Most of the compounds appear to have BBB permeability and low toxicity risks. Hence, they may be synthesized and screened for their CNS activity.
Published Version
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