Evaluation of (E)-1-Phenyl-N-(2-Phenyl)-1,3-Benzoxazol-6-yl) Methanimine Derivatives for In Vitro Inhibition of Sirt2 Enzyme in Parkinson’s Disease

Malligarjunan, Navinkumar; Jeeru, Tejaswini Reddy; Swaminathan, Gomathi

doi:10.48309/ajgc.2026.558256.1866

Evaluation of (E)-1-Phenyl-N-(2-Phenyl)-1,3-Benzoxazol-6-yl) Methanimine Derivatives for In Vitro Inhibition of Sirt2 Enzyme in Parkinson’s Disease

Document Type : Original Research Article

Authors

Navinkumar Malligarjunan

Tejaswini Reddy Jeeru

Gomathi Swaminathan

Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India

https://doi.org/10.48309/ajgc.2026.558256.1866

Abstract

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. In vitro assays further demonstrated notable SIRT2 inhibition, with IC₅₀ values comparable to or superior to the reference drug Memantine. Among the tested molecules, NOV 3 displayed the most potent activity, identifying it as a promising lead compound for developing new therapeutic agents against Parkinson’s disease.

Graphical Abstract

Keywords

SIRT2

Parkinson&rsquo

s disease

Benzoxazole

Molecular docking

In vitro

Subjects

Organic Chemistry

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