TY  - 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 . .

TY  - 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/123456789/2905
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 . .

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 .