Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase

Sukhorukov, Alexey Yu. and Anilkumar, C. N. and Swamy, Jagadish and Sema, L. Ioffe and Nanjunda Swamy, S. and Rangappa, K. S. and Basappa, (2014) Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase. Bioorganic & Medicinal Chemistry Letters. pp. 1-4. ISSN 0960-894X

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Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 μM, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of −1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (log P = 2.66), suggesting a potential ability to penetrate the blood–brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer’s agents.

Item Type: Article
Additional Information: Unmapped bibliographic data: JO - Bioorganic & Medicinal Chemistry Letters [Field not mapped to EPrints]
Uncontrolled Keywords: Chemical biology, Oxazine, Acetylcholinesterase, Lipoxygenase, Alzheimer disease
Subjects: Physical Sciences > Chemistry
Divisions: PG Campuses > Manasagangotri, Mysore > Chemistry
Depositing User: Praveen Kumari B.L
Date Deposited: 16 Jun 2014 05:39
Last Modified: 06 Oct 2015 05:35

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