In silico analysis
of Juarezic acid and Avenalumic acid analogs
Kuchana Madhavi, Chelimela Ramya, Mandyam Srinivasulu Puja Sri and Shaik Naailah
Sulthana
Res. J. Chem. Environ.; Vol. 29(1); 31-38;
doi: https://doi.org/10.25303/291rjce031038; (2025)
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.
