Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase
Само за регистроване кориснике
2019
Чланак у часопису (Објављена верзија)
,
Elsevier
Метаподаци
Приказ свих података о документуАпстракт
Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a... stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.
Кључне речи:
Cholinesterase / Alzheimer's disease / pKa values / Quinoline-based compounds / selectivity / docking / DFTИзвор:
Chemico-Biological Interactions, 2019, 308, 101-109Издавач:
- Elsevier Ireland Ltd
Финансирање / пројекти:
- Рационални дизајн и синтеза биолошки активних и координационих једињења и функционалних материјала, релевантних у (био)нанотехнологији (RS-MESTD-Basic Research (BR or ON)-172035)
- Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-MESTD-Basic Research (BR or ON)-172008)
- Croatian Science Foundation (IP-2018-01-7683)
Напомена:
- Peer-reviewed version: http://cer.ihtm.bg.ac.rs/handle/123456789/2905
DOI: 10.1016/j.cbi.2019.05.024
ISSN: 0009-2797
PubMed: 31100281
WoS: 000474214200010
Scopus: 2-s2.0-85065775348
Институција/група
IHTMTY - JOUR AU - Bosak, Anita AU - Opsenica, Dejan AU - Šinko, Goran AU - Zlatar, Matija AU - Kovarik, Zrinka PY - 2019 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2886 AB - Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V. PB - Elsevier Ireland Ltd T2 - Chemico-Biological Interactions T1 - Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase VL - 308 SP - 101 EP - 109 DO - 10.1016/j.cbi.2019.05.024 ER -
@article{ author = "Bosak, Anita and Opsenica, Dejan and Šinko, Goran and Zlatar, Matija and Kovarik, Zrinka", year = "2019", abstract = "Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.", publisher = "Elsevier Ireland Ltd", journal = "Chemico-Biological Interactions", title = "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase", volume = "308", pages = "101-109", doi = "10.1016/j.cbi.2019.05.024" }
Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z.. (2019). Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions Elsevier Ireland Ltd., 308, 101-109. https://doi.org/10.1016/j.cbi.2019.05.024
Bosak A, Opsenica D, Šinko G, Zlatar M, Kovarik Z. Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions. 2019;308:101-109. doi:10.1016/j.cbi.2019.05.024 .
Bosak, Anita, Opsenica, Dejan, Šinko, Goran, Zlatar, Matija, Kovarik, Zrinka, "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase" in Chemico-Biological Interactions, 308 (2019):101-109, https://doi.org/10.1016/j.cbi.2019.05.024 . .