TY  - JOUR
AU  - Bondžić, Aleksandra M.
AU  - Senćanski, Milan V.
AU  - Vujačić Nikezić, Ana V.
AU  - Kirillova, Marina V.
AU  - André, Vania
AU  - Kirillov, Alexander M.
AU  - Bondžić, Bojan P.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8806
AB  - Three coordination compounds featuring different types of tetracopper(II) cores, namely [O ⊂ Cu4N(CH2CH2O)34(BOH)4][BF4]2 (1), [Cu4(μ4-H2edte)(μ5-H2edte)(sal)2]n·7nH2O, (H4edte = N,N,N′,N′-tetrakis(2-hydroxyethyl)ethylenediamine, H2sal = salicylic acid) (2), and [Cu4(μ3-Hbes)4(μ-hba)K(H2O)3]n, H3bes = N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (3), were assayed for their potency to inhibit the acetyl (AChE) and butyrylcholinesterase (BuChE) enzymes aiming to test these compounds as potential dual inhibitors in the treatment of Alzheimer's disease. All the investigated compounds showed a strong inhibitory potency toward both enzymes with IC50 values in micromolar range of concentration; compound 1 displayed the most potent inhibitory behaviour toward both enzymes. The mechanism of the AChE and BuChE inhibition was examined by enzyme kinetic measurements. The obtained kinetic parameters, Vmax and Km indicated an uncompetitive type of inhibition of both enzymes by compound 1. For the other two compounds a non-competitive inhibition mode was observed. To get further insight into the mechanism of action and to elucidate binding modes in details we examined the interactions of 1–3 with acetylcholinesterase, using molecular docking approach. Grid based docking studies indicated that these compounds can bind to peripheral anionic site (PAS) of the AChE with Ki values in micromolar range. Moreover, blind docking revealed the capability of investigated compounds to bind to new allosteric site (i.e. binding site II) distinct from PAS. Showing that these Cu-based compounds can act as new allosteric inhibitors of AChE and identifying novel allosteric binding site on AChE represents a significant contribution toward the design of novel and more effective inhibitors of AChE. © 2020 Elsevier Inc.
T2  - Journal of Inorganic Biochemistry
T1  - Aminoalcoholate-driven tetracopper(II) cores as dual acetyl and butyrylcholinesterase inhibitors: Experimental and theoretical elucidation of mechanism of action
VL  - 205
SP  - 110990
DO  - 10.1016/j.jinorgbio.2019.110990
ER  - 

@article{
author = "Bondžić, Aleksandra M. and Senćanski, Milan V. and Vujačić Nikezić, Ana V. and Kirillova, Marina V. and André, Vania and Kirillov, Alexander M. and Bondžić, Bojan P.",
year = "2020",
abstract = "Three coordination compounds featuring different types of tetracopper(II) cores, namely [O ⊂ Cu4N(CH2CH2O)34(BOH)4][BF4]2 (1), [Cu4(μ4-H2edte)(μ5-H2edte)(sal)2]n·7nH2O, (H4edte = N,N,N′,N′-tetrakis(2-hydroxyethyl)ethylenediamine, H2sal = salicylic acid) (2), and [Cu4(μ3-Hbes)4(μ-hba)K(H2O)3]n, H3bes = N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (3), were assayed for their potency to inhibit the acetyl (AChE) and butyrylcholinesterase (BuChE) enzymes aiming to test these compounds as potential dual inhibitors in the treatment of Alzheimer's disease. All the investigated compounds showed a strong inhibitory potency toward both enzymes with IC50 values in micromolar range of concentration; compound 1 displayed the most potent inhibitory behaviour toward both enzymes. The mechanism of the AChE and BuChE inhibition was examined by enzyme kinetic measurements. The obtained kinetic parameters, Vmax and Km indicated an uncompetitive type of inhibition of both enzymes by compound 1. For the other two compounds a non-competitive inhibition mode was observed. To get further insight into the mechanism of action and to elucidate binding modes in details we examined the interactions of 1–3 with acetylcholinesterase, using molecular docking approach. Grid based docking studies indicated that these compounds can bind to peripheral anionic site (PAS) of the AChE with Ki values in micromolar range. Moreover, blind docking revealed the capability of investigated compounds to bind to new allosteric site (i.e. binding site II) distinct from PAS. Showing that these Cu-based compounds can act as new allosteric inhibitors of AChE and identifying novel allosteric binding site on AChE represents a significant contribution toward the design of novel and more effective inhibitors of AChE. © 2020 Elsevier Inc.",
journal = "Journal of Inorganic Biochemistry",
title = "Aminoalcoholate-driven tetracopper(II) cores as dual acetyl and butyrylcholinesterase inhibitors: Experimental and theoretical elucidation of mechanism of action",
volume = "205",
pages = "110990",
doi = "10.1016/j.jinorgbio.2019.110990"
}

Bondžić, A. M., Senćanski, M. V., Vujačić Nikezić, A. V., Kirillova, M. V., André, V., Kirillov, A. M.,& Bondžić, B. P.. (2020). Aminoalcoholate-driven tetracopper(II) cores as dual acetyl and butyrylcholinesterase inhibitors: Experimental and theoretical elucidation of mechanism of action. in Journal of Inorganic Biochemistry, 205, 110990.
https://doi.org/10.1016/j.jinorgbio.2019.110990

Bondžić AM, Senćanski MV, Vujačić Nikezić AV, Kirillova MV, André V, Kirillov AM, Bondžić BP. Aminoalcoholate-driven tetracopper(II) cores as dual acetyl and butyrylcholinesterase inhibitors: Experimental and theoretical elucidation of mechanism of action. in Journal of Inorganic Biochemistry. 2020;205:110990.
doi:10.1016/j.jinorgbio.2019.110990 .

Bondžić, Aleksandra M., Senćanski, Milan V., Vujačić Nikezić, Ana V., Kirillova, Marina V., André, Vania, Kirillov, Alexander M., Bondžić, Bojan P., "Aminoalcoholate-driven tetracopper(II) cores as dual acetyl and butyrylcholinesterase inhibitors: Experimental and theoretical elucidation of mechanism of action" in Journal of Inorganic Biochemistry, 205 (2020):110990,
https://doi.org/10.1016/j.jinorgbio.2019.110990 . .

TY  - JOUR
AU  - Bondzic, Bojan P.
AU  - Dzambaski, Zdravko
AU  - Bondžić, Aleksandra M.
AU  - Markovic, Rade
PY  - 2012
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5127
AB  - The a-C position in 4-oxo thiazolidinones functions as one of the three possible nucleophilic sites in these molecules. We used the inherent reactivity of alpha-C of the exocyclic double bond (a so called push pull system) to obtain bicyclic fused thiazolidinones via pi-annulation cyclization. Appropriate reaction conditions to selectively activate this position and secondary nitrogen towards N, pi-annulation were found. Furthermore, the intramolecular vinylogous iminium ion 6-exo-trig cyclization was used to access fused bicyclic precursors for the pi-annulation in order to obtain the novel tricyclic structures stereoselectively. (c) 2012 Elsevier Ltd. All rights reserved.
T2  - Tetrahedron
T1  - pi-Annulation reactions of 4-thiazolidinone enaminones in the synthesis of fused bi- and tri-cyclic compounds
VL  - 68
IS  - 47
SP  - 9556
EP  - 9565
DO  - 10.1016/j.tet.2012.09.080
ER  - 

@article{
author = "Bondzic, Bojan P. and Dzambaski, Zdravko and Bondžić, Aleksandra M. and Markovic, Rade",
year = "2012",
abstract = "The a-C position in 4-oxo thiazolidinones functions as one of the three possible nucleophilic sites in these molecules. We used the inherent reactivity of alpha-C of the exocyclic double bond (a so called push pull system) to obtain bicyclic fused thiazolidinones via pi-annulation cyclization. Appropriate reaction conditions to selectively activate this position and secondary nitrogen towards N, pi-annulation were found. Furthermore, the intramolecular vinylogous iminium ion 6-exo-trig cyclization was used to access fused bicyclic precursors for the pi-annulation in order to obtain the novel tricyclic structures stereoselectively. (c) 2012 Elsevier Ltd. All rights reserved.",
journal = "Tetrahedron",
title = "pi-Annulation reactions of 4-thiazolidinone enaminones in the synthesis of fused bi- and tri-cyclic compounds",
volume = "68",
number = "47",
pages = "9556-9565",
doi = "10.1016/j.tet.2012.09.080"
}

Bondzic, B. P., Dzambaski, Z., Bondžić, A. M.,& Markovic, R.. (2012). pi-Annulation reactions of 4-thiazolidinone enaminones in the synthesis of fused bi- and tri-cyclic compounds. in Tetrahedron, 68(47), 9556-9565.
https://doi.org/10.1016/j.tet.2012.09.080

Bondzic BP, Dzambaski Z, Bondžić AM, Markovic R. pi-Annulation reactions of 4-thiazolidinone enaminones in the synthesis of fused bi- and tri-cyclic compounds. in Tetrahedron. 2012;68(47):9556-9565.
doi:10.1016/j.tet.2012.09.080 .

Bondzic, Bojan P., Dzambaski, Zdravko, Bondžić, Aleksandra M., Markovic, Rade, "pi-Annulation reactions of 4-thiazolidinone enaminones in the synthesis of fused bi- and tri-cyclic compounds" in Tetrahedron, 68, no. 47 (2012):9556-9565,
https://doi.org/10.1016/j.tet.2012.09.080 . .