Exploration of newly synthesized sulfonohydrazides as potential enzyme inhibitors: synthesis, characterization, and <i>in silico</i> studies

<p>To synthesize novel sulfonohydrazide derivatives and evaluate their physicochemical and enzyme‑inhibitory profiles, together with the corresponding structure–activity relationships.</p> <p>A series of six hydrazide derivatives (NLs₁–NLs₆) was synthesized and subjected to comprehensive <i>in vitro</i> enzymatic evaluation against four critical targets: 15-Lipoxygenase (15-LOX), Carbonic anhydrase II (β-CA-II), Butyrylcholinesterase (BChE), and Acetylcholinesterase (AChE).

Furthermore, to determine the stability and binding of the synthesized compounds, molecular dynamic simulations and molecular docking were performed.</p> <p>Bromo- and fluoro-substituted NLs₂ (IC₅₀ = 0.29 ± 0.02 µM) and NLs₃ (IC₅₀ = 0.54 ± 0.01 µM) showed significant activity against AChE. Furthermore, compound NLs₄ demonstrated significant cholinesterase inhibitory activities, i.e. AChE and BChE, although the inhibitory potential against AChE (IC₅₀ = 0.72 ± 0.11 µM) was comparatively higher than that of BChE (IC₅₀ = 0.65 ± 0.03 µM).