TY  - JOUR
AU  - Gajić, Mihajlo
AU  - Džambaski, Zdravko
AU  - Ilić, Budimir S.
AU  - Kocić, Gordana
AU  - Bondžić, Bojan
AU  - Šmelcerović, Andrija
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4729
AB  - In this study, seven new 4-oxothiazolidine derivatives were synthesized and assayed, along 7 known derivatives, for inhibitory properties against deoxyribonuclease I (DNase I) and xanthine oxidase (XO) in vitro. Among tested compounds, (5Z)-Ethyl-2-(2-(cyanomethylene)-4-oxothiazolidin-5-yliden)acetate (6) exhibited inhibitory activity against both enzymes (DNase I IC50 = 67.94 ± 5.99 μM; XO IC50 = 98.98 ± 13.47 μM), therefore being the first reported dual inhibitor of DNase I and XO. Observed DNase I inhibition qualifies compound 6 as the most potent small organic DNase I inhibitor reported so far. Derivatives of 2-alkyliden-4-oxothiazolidinone (1) inhibited DNase I below 200 μM, while the other tested 4-oxothiazolidine derivatives remained inactive against both enzymes. The molecular docking and molecular dynamics simulations into the binding sites of DNase I and XO enzyme allowed us to clarify the binding modes of this 4-oxothiazolidine derivative, which might aid future development of dual DNase I and XO.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Synthesis and analysis of 4-oxothiazolidines as potential dual inhibitors of deoxyribonuclease I and xanthine oxidase
VL  - 345
SP  - 109536
DO  - 10.1016/j.cbi.2021.109536
ER  - 

@article{
author = "Gajić, Mihajlo and Džambaski, Zdravko and Ilić, Budimir S. and Kocić, Gordana and Bondžić, Bojan and Šmelcerović, Andrija",
year = "2021",
abstract = "In this study, seven new 4-oxothiazolidine derivatives were synthesized and assayed, along 7 known derivatives, for inhibitory properties against deoxyribonuclease I (DNase I) and xanthine oxidase (XO) in vitro. Among tested compounds, (5Z)-Ethyl-2-(2-(cyanomethylene)-4-oxothiazolidin-5-yliden)acetate (6) exhibited inhibitory activity against both enzymes (DNase I IC50 = 67.94 ± 5.99 μM; XO IC50 = 98.98 ± 13.47 μM), therefore being the first reported dual inhibitor of DNase I and XO. Observed DNase I inhibition qualifies compound 6 as the most potent small organic DNase I inhibitor reported so far. Derivatives of 2-alkyliden-4-oxothiazolidinone (1) inhibited DNase I below 200 μM, while the other tested 4-oxothiazolidine derivatives remained inactive against both enzymes. The molecular docking and molecular dynamics simulations into the binding sites of DNase I and XO enzyme allowed us to clarify the binding modes of this 4-oxothiazolidine derivative, which might aid future development of dual DNase I and XO.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Synthesis and analysis of 4-oxothiazolidines as potential dual inhibitors of deoxyribonuclease I and xanthine oxidase",
volume = "345",
pages = "109536",
doi = "10.1016/j.cbi.2021.109536"
}

Gajić, M., Džambaski, Z., Ilić, B. S., Kocić, G., Bondžić, B.,& Šmelcerović, A.. (2021). Synthesis and analysis of 4-oxothiazolidines as potential dual inhibitors of deoxyribonuclease I and xanthine oxidase. in Chemico-Biological Interactions
Elsevier., 345, 109536.
https://doi.org/10.1016/j.cbi.2021.109536

Gajić M, Džambaski Z, Ilić BS, Kocić G, Bondžić B, Šmelcerović A. Synthesis and analysis of 4-oxothiazolidines as potential dual inhibitors of deoxyribonuclease I and xanthine oxidase. in Chemico-Biological Interactions. 2021;345:109536.
doi:10.1016/j.cbi.2021.109536 .

Gajić, Mihajlo, Džambaski, Zdravko, Ilić, Budimir S., Kocić, Gordana, Bondžić, Bojan, Šmelcerović, Andrija, "Synthesis and analysis of 4-oxothiazolidines as potential dual inhibitors of deoxyribonuclease I and xanthine oxidase" in Chemico-Biological Interactions, 345 (2021):109536,
https://doi.org/10.1016/j.cbi.2021.109536 . .