4-Aminoqionolines as reversible inhibitors of human cholinesterase activity
Апстракт
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 deve...lopment of new inhibitors of AChE and potential drugs for treatment of neurodegenerative diseases.
Кључне речи:
acetylcholinesterase / butyrylcholinesterase / treatment / 4-aminoquinoline / Alzheimer’s disease / DockingИзвор:
Military Medical Science Letters, 2018, 87, Suppl. 1, 83-83Издавач:
- Faculty of Military Health Sciences, Czech Republic
Финансирање / пројекти:
- Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-172008)
- Рационални дизајн и синтеза биолошки активних и координационих једињења и функционалних материјала, релевантних у (био)нанотехнологији (RS-172035)
Напомена:
- 13th International Meeting on Cholinesterases and and the 7th International Conference on Paraoxonases, 9th to 14th of September 2018 Hradec Králové, Czech Republic
Институција/група
IHTMTY - CONF AU - Bosak, Anita AU - Opsenica, Dejan AU - Šinko, Goran AU - Zlatar, Matija AU - Kovarik, Zrinka PY - 2018 UR - https://mmsl.cz/artkey/mms-201888-0083.php UR - https://cer.ihtm.bg.ac.rs/handle/123456789/3216 AB - 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. PB - Faculty of Military Health Sciences, Czech Republic C3 - Military Medical Science Letters T1 - 4-Aminoqionolines as reversible inhibitors of human cholinesterase activity VL - 87 IS - Suppl. 1 SP - 83 EP - 83 UR - https://hdl.handle.net/21.15107/rcub_cer_3216 ER -
@conference{ author = "Bosak, Anita and Opsenica, Dejan and Šinko, Goran and Zlatar, Matija and Kovarik, Zrinka", year = "2018", abstract = "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.", publisher = "Faculty of Military Health Sciences, Czech Republic", journal = "Military Medical Science Letters", title = "4-Aminoqionolines as reversible inhibitors of human cholinesterase activity", volume = "87", number = "Suppl. 1", pages = "83-83", url = "https://hdl.handle.net/21.15107/rcub_cer_3216" }
Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z.. (2018). 4-Aminoqionolines as reversible inhibitors of human cholinesterase activity. in Military Medical Science Letters Faculty of Military Health Sciences, Czech Republic., 87(Suppl. 1), 83-83. https://hdl.handle.net/21.15107/rcub_cer_3216
Bosak A, Opsenica D, Šinko G, Zlatar M, Kovarik Z. 4-Aminoqionolines as reversible inhibitors of human cholinesterase activity. in Military Medical Science Letters. 2018;87(Suppl. 1):83-83. https://hdl.handle.net/21.15107/rcub_cer_3216 .
Bosak, Anita, Opsenica, Dejan, Šinko, Goran, Zlatar, Matija, Kovarik, Zrinka, "4-Aminoqionolines as reversible inhibitors of human cholinesterase activity" in Military Medical Science Letters, 87, no. Suppl. 1 (2018):83-83, https://hdl.handle.net/21.15107/rcub_cer_3216 .