ЦЕР - Централни Репозиторијум ИХТМ-а
Институт за хемију, технологију и металургију
    • English
    • Српски
    • Српски (Serbia)
  • Српски (ћирилица) 
    • Енглески
    • Српски (ћирилица)
    • Српски (латиница)
  • Пријава
Преглед рада 
  •   ЦЕР - Централни репозиторијум ИХТМ-а
  • IHTM
  • Radovi istraživača / Researchers' publications
  • Преглед рада
  •   ЦЕР - Централни репозиторијум ИХТМ-а
  • IHTM
  • Radovi istraživača / Researchers' publications
  • Преглед рада
JavaScript is disabled for your browser. Some features of this site may not work without it.

Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase

Само за регистроване кориснике
2019
Аутори
Bosak, Anita
Opsenica, Dejan
Šinko, Goran
Zlatar, Matija
Kovarik, Zrinka
Чланак у часопису (Објављена верзија)
,
Elsevier
Метаподаци
Приказ свих података о документу
Апстракт
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 / DFT
Извор:
Chemico-Biological Interactions, 2019, 308, 101-109
Издавач:
  • Elsevier Ireland Ltd
Пројекти:
  • Рационални дизајн и синтеза биолошки активних и координационих једињења и функционалних материјала, релевантних у (био)нанотехнологији (RS-172035)
  • Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-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
[ Google Scholar ]
7
7
URI
http://cer.ihtm.bg.ac.rs/handle/123456789/2886
Колекције
  • Radovi istraživača / Researchers' publications
Институција
IHTM
TY  - JOUR
AU  - Bosak, Anita
AU  - Opsenica, Dejan
AU  - Šinko, Goran
AU  - Zlatar, Matija
AU  - Kovarik, Zrinka
PY  - 2019
UR  - http://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",
url = "http://cer.ihtm.bg.ac.rs/handle/123456789/2886",
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. Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. Chemico-Biological Interactions. 2019;308:101-109
Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z. (2019). Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase.
Chemico-Biological InteractionsElsevier Ireland Ltd., 308, 101-109.
https://doi.org/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" 308 (2019):101-109,
https://doi.org/10.1016/j.cbi.2019.05.024 .

DSpace software copyright © 2002-2015  DuraSpace
О Централном репозиторијуму (ЦеР) | Пошаљите запажања

OpenAIRERCUB
 

 

Комплетан репозиторијумИнституцијеАуториНасловиТемеОва институцијаАуториНасловиТеме

Статистика

Преглед статистика

DSpace software copyright © 2002-2015  DuraSpace
О Централном репозиторијуму (ЦеР) | Пошаљите запажања

OpenAIRERCUB