dc.creator | Bosak, Anita | |
dc.creator | Opsenica, Dejan | |
dc.creator | Šinko, Goran | |
dc.creator | Zlatar, Matija | |
dc.creator | Kovarik, Zrinka | |
dc.date.accessioned | 2019-05-30T01:17:48Z | |
dc.date.available | 2020-06-15 | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0009-2797 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/2905 | |
dc.description.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. | en |
dc.language.iso | en | |
dc.publisher | Elsevier Ireland Ltd | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS// | |
dc.relation | Croatian Science Foundation (IP-2018-01-7683) | |
dc.rights | embargoedAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Chemico-Biological Interactions | |
dc.subject | Cholinesterase | |
dc.subject | Alzheimer's disease | |
dc.subject | pKa values | |
dc.subject | Quinoline-based compounds | |
dc.subject | selectivity | |
dc.subject | docking | |
dc.subject | DFT | |
dc.title | Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase | en |
dc.type | article | en |
dc.rights.license | BY-NC-ND | |
dcterms.abstract | Шинко, Горан; Опсеница, Дејан; Златар, Матија; Босак, Aнита; Коварик, Зринка; | |
dc.rights.holder | Elsevier | |
dc.citation.volume | 308 | |
dc.citation.spage | 101 | |
dc.citation.epage | 109 | |
dc.citation.rank | M21 | |
dc.description.other | This is peer-reviewed version of the article: [https://doi.org/10.1016/j.cbi.2019.05.024] | |
dc.description.other | [http://cer.ihtm.bg.ac.rs/handle/123456789/2886] | |
dc.identifier.pmid | 31100281 | |
dc.identifier.doi | 10.1016/j.cbi.2019.05.024 | |
dc.identifier.fulltext | https://cer.ihtm.bg.ac.rs/bitstream/id/7042/10.1016@j.cbi.2019.05.024.pdf | |
dc.identifier.scopus | 2-s2.0-85065775348 | |
dc.identifier.wos | 000474214200010 | |
dc.type.version | acceptedVersion | |