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

Sukhorukov, A. Y. and Nirvanappa, A. C. and Swamy, J. and Ioffe, S. L. and Nanjunda Swamy, S. and Basappa and Rangappa, K. S. (2014) Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase. Bioorganic and Medicinal Chemistry Letters, 24 (15). pp. 3618-3621. 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
Uncontrolled Keywords: Article, concentration response, controlled study, drug potency, drug synthesis, IC50, nonhuman, structure activity relation, unclassified drug, chemical structure, chemistry, drug screening, Molecular Structure, Structure-Activity Relationship, synthesis, dose response, Dose-Response Relationship, Drug, metabolism, molecular docking, enzyme active site, 1, 6 dimethyl 4 phenyl 5, computer model, enzyme inhibition, article, acetylcholinesterase, cholinesterase inhibition, cholinesterase inhibitor, molecular library, Small Molecule Libraries, nuclear magnetic resonance spectroscopy, Acetylcholinesterase, Models, Alzheimer disease, drug protein binding, IC 50, lipophilicity, drug penetration, Molecular, oxazine derivative, Oxazines, 2 (2 acetyl 6, 2 (acetyl 6, 2 oxazin 3 yl)methyl] 1h isoindole 1, 2 oxazine derivative, 2-((2-acetyl-6, 2-oxazin-3-yl)methyl)-1H-isoindole-1, 3(2h) dione, 3(2H)-dione, 6 dihydro 2h 1, 6-dihydro-2H-1, 6-dimethyl-4-phenyl-5, arachidonate 5 lipoxygenase, Arachidonate 5-Lipoxygenase, blood brain barrier, Cholinesterase Inhibitors, lipoxygenase inhibitor, Lipoxygenase Inhibitors, neostigmine, pharmacology, phthalimide derivative, Phthalimides
Subjects: C Chemical Science > Chemistry
Divisions: Department of > Chemistry
Depositing User: Arshiya Kousar Library Assistant
Date Deposited: 31 Aug 2019 06:22
Last Modified: 31 Aug 2019 06:22

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