期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 24, 期 15, 页码 3618-3621出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2014.05.040
关键词
Chemical biology; Oxazine; Acetylcholinesterase; Lipoxygenase; Alzheimer disease
资金
- Foundation for the Support of Small-scale Enterprises [76GU1/2013]
- President's grant council [MK-3918.2013.3]
- University Grants Commission [41-257-2012-SR]
- Vision Group Science and Technology, Department of Science and Technology (DST) [SR/FT/LS-142/2012]
- DST
- Karnataka University, INDIA
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-dimethy1-4-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 mu M, 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 (logP = 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. (C) 2014 Elsevier Ltd. All rights reserved.
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