Substituted Methanimine Derivatives: Neurodegenerative 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 2 (SIRT2), a class III histone deacetylase, is known to influence key cellular functions such as genome integrity, mitochondrial regulation, autophagy, and apoptosis. Increased SIRT2 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)-1-Phenyl-N-(2-Phenyl)-1,3-benzoxazol-6-yl) methanimine analogues (NOV 1-3), were designed and evaluated for their inhibitory potential against SIRT2. The target protein (PDB ID: 5YQL) was obtained from the RCSB PDB database, refined through loop modelling, and energy-minimized before molecular docking analysis. Docking studies showed that NOV 1-3 exhibited strong binding affinities and key interactions within the SIRT2 active site, suggesting effective inhibition. The synthesized compounds were structurally confirmed using IR, NMR, and mass spectroscopy.