Synthesis and analysis of 4-oxothiazolidines as potential dual inhibitors of deoxyribonuclease I and xanthine oxidase
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2021
Authors
Gajić, MihajloDžambaski, Zdravko
Ilić, Budimir S.
Kocić, Gordana
Bondžić, Bojan
Šmelcerović, Andrija
Article (Published version)
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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.
Keywords:
DNases / Oxidoreductases / Enzyme inhibition / Thiazolidinones / Molecular dynamicsSource:
Chemico-Biological Interactions, 2021, 345, 109536-Publisher:
- Elsevier
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200113 (Univeristy of Niš, Faculty of Medicine) (RS-MESTD-inst-2020-200113)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-MESTD-inst-2020-200026)
- Faculty of Medicine of the University of Niš (Internal project No. 40)
DOI: 10.1016/j.cbi.2021.109536
ISSN: 0009-2797
PubMed: 34058176
WoS: 000681131700007
Scopus: 2-s2.0-85108103742
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IHTMTY - 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 . .