Synthesis of Some Oxime Derivatives as Novel Elastase Inhibitors: Molecular Dynamics Studies and Computational Insight

ABSTRACT

Oximes and oxime ethers are important compounds in organic chemistry, both structurally and in terms of applications. The biological properties of oximes are directly related to the chemical properties of their functional groups, metal‐binding capacities, and ability to interact with biological targets in a multifaceted way. This study presents the synthesis of 5‐hydroxyimino 2a‐b and 5‐methoxyimino 2c derivatives from 5‐oxo pentanoic acid methyl esters ( 1a‐c ) containing phenyl, p‐chlorophenyl, and thiophenyl groups, elucidation of their structures through various spectroscopic analysis methods (IR, ¹ H NMR, ¹³ C NMR, MS, and elemental analysis), and investigation of their elastase inhibition activities. In the elastase inhibition results, compounds were found to exhibit antielastase activity. Compound 2a , containing the p ‐chlorophenyl substituent, had the highest antielastase activity (IC ₅₀  = 426.68 ± 46.90 µM) and was found to have a lower IC ₅₀ value compared to the positive control, ursolic acid (486.19 ± 44.22 µM). Furthermore, molecular docking was used to predict binding affinities and found to be −5.8 kcal/mol for compound 2a and −6.8 kcal/mol for ursolic acid. Molecular dynamics simulations were conducted to evaluate the stability of protein–ligand interactions. These results suggest that compound 2a could be a potential elastase inhibitor candidate and scaffold for pharmaceutical or cosmetic applications.