engleski

4-aminoquinilines as reversible inhibitors of human cholinesterase activity

We synthesised eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7) carbon of 4-aminoquinoline, and tested their potency to inhibit human AChE and BChE. All of the compounds reversibly inhibited both enzymes with dissociation inhibition (Ki) constants from 0.50 to 50 µM exhibiting selectivity. In other words, for all compounds, AChE exhibited higher affinity than BChE. The most potent inhibitors of AChE were compounds with an octyl chain or adamantane, regardless of the group in position C(7). The shortening of the chain length caused the AChE inhibition decrease by 5-20 times. Docking studies made it clear that the high AChE affinity resulted from simultaneous interactions of the quinoline group with aromatic residues of both the catalytic active site and the peripheral site. In conclusion, the inhibition potency and selectivity classify several novel compounds as leads for further modification and optimization towards the development of new inhibitors of AChE and potential drugs for treatment of neurodegenerative diseases. Key words: acetylcholinesterase, butyrylcholinesterase, treatment, 4-aminoquinoline, Alzheimer’s disease Acknowledgment: this study was financed by the Croatian Science Foundation (Grant. No. 4307) and Ministry of Science and Technological Development of Serbia (Grants no. 172008 and 172035)

acetylcholinesterase, butyrylcholinesterase, treatment, 4-aminoquinoline, Alzheimer’s disease

This study was financed by the Croatian Science Foundation (Grant. No. 4307) and Ministry of Science and Technological Development of Serbia (Grants no. 172008 and 172035)