engleski

Design, synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans- 4/5- arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans- amino- 4-/5-arylethenyl- oxazoles were designed and synthesized by the Buchwald- Hartwig amination of a previously synthesized trans- chloro- arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino- 4-/5- arylethenyl-oxazole derivatives which inhibited BChE (IC50 in µM range) potently and AChE (IC50>>100 µM) poorly. Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.

arylethenyl-oxazole ; benzylamine ; cholinesterase ; electrocyclization ; naphthoxazole ; synthesis

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