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4-Aminoqionolines as reversible inhibitors of human cholinesterase activity

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2018
954584.MMSL_mms-201888-0083.pdf (65.10Kb)
Authors
Bosak, Anita
Opsenica, Dejan
Šinko, Goran
Zlatar, Matija
Kovarik, Zrinka
Conference object (Published version)
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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 deve...lopment of new inhibitors of AChE and potential drugs for treatment of neurodegenerative diseases.

Keywords:
acetylcholinesterase / butyrylcholinesterase / treatment / 4-aminoquinoline / Alzheimer’s disease / Docking
Source:
Military Medical Science Letters, 2018, 87, Suppl. 1, 83-83
Publisher:
  • Faculty of Military Health Sciences, Czech Republic
Funding / projects:
  • The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
  • Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-172035)
Note:
  • 13th International Meeting on Cholinesterases and and the 7th International Conference on Paraoxonases, 9th to 14th of September 2018 Hradec Králové, Czech Republic

ISSN: 0372-7025

[ Google Scholar ]
Handle
https://hdl.handle.net/21.15107/rcub_cer_3216
URI
https://mmsl.cz/artkey/mms-201888-0083.php
https://cer.ihtm.bg.ac.rs/handle/123456789/3216
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
IHTM
TY  - 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 .

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