Evaluation of (<em style="mso-bidi-font-style: normal;">E)-۱-Phenyl-<em style="mso-bidi-font-style: normal;">N-(۲-Phenyl)-۱,۳-Benzoxazol-۶-yl) Methanimine Derivatives for In Vitro Inhibition of Sirt۲ Enzyme in Parkinson’s Disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the striatum and the presence of Lewy bodies composed mainly of α-synuclein. Sirtuin ۲ (SIRT۲), a class III histone deacetylase, is known to influence key cellular functions such as genome integrity, mitochondrial regulation, autophagy, and apoptosis. Increased SIRT۲ expression in aging and PD models highlights its relevance as a potential therapeutic target. In this study, a set of benzoxazole-based methanimine derivatives, (E)-۱-Phenyl-N-(۲-phenyl)-۱,۳-benzoxazol-۶-yl) methanimine analogues (NOV ۱–۳), were designed and evaluated for their inhibitory potential against SIRT۲. The target protein (PDB ID: ۵YQL) was obtained from the RCSB PDB database, refined through loop modelling, and energy-minimized before molecular docking analysis. Docking studies showed that NOV ۱–۳ exhibited strong binding affinities and key interactions within the SIRT۲ active site, suggesting effective inhibition. The synthesized compounds were structurally confirmed using IR, NMR, and mass spectroscopy. In vitro assays further demonstrated notable SIRT۲ inhibition, with IC₅₀ values comparable to or superior to the reference drug Memantine. Among the tested molecules, NOV ۳ displayed the most potent activity, identifying it as a promising lead compound for developing new therapeutic agents against Parkinson’s disease.

کلیدواژه ها:

SIRT۲ ، Parkinson&rsquo ، s disease ، Benzoxazole ، Molecular docking ، In vitro