TY  - JOUR
AU  - Gajić, Mihajlo
AU  - Ilić, Budimir S.
AU  - Bondžić, Bojan
AU  - Džambaski, Zdravko
AU  - Kojić, Vesna V.
AU  - Jakimov, Dimitar S.
AU  - Kocić, Gordana
AU  - Šmelcerović, Andrija
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4815
AB  - Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC50 values below 200 μM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (2) (IC50=134.35±11.38 μM) exhibiting slightly better IC50 value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one (15) (IC50=147.51±14.87 μM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (18) (IC50=149.07±2.98 μM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (22) (IC50=148.31±2.96 μM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.
PB  - Wiley
T2  - Chemistry and Biodisversity
T1  - 1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors
VL  - 18
IS  - 8
SP  - e2100261
DO  - 10.1002/cbdv.202100261
ER  - 

@article{
author = "Gajić, Mihajlo and Ilić, Budimir S. and Bondžić, Bojan and Džambaski, Zdravko and Kojić, Vesna V. and Jakimov, Dimitar S. and Kocić, Gordana and Šmelcerović, Andrija",
year = "2021",
abstract = "Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC50 values below 200 μM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (2) (IC50=134.35±11.38 μM) exhibiting slightly better IC50 value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one (15) (IC50=147.51±14.87 μM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (18) (IC50=149.07±2.98 μM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (22) (IC50=148.31±2.96 μM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.",
publisher = "Wiley",
journal = "Chemistry and Biodisversity",
title = "1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors",
volume = "18",
number = "8",
pages = "e2100261",
doi = "10.1002/cbdv.202100261"
}

Gajić, M., Ilić, B. S., Bondžić, B., Džambaski, Z., Kojić, V. V., Jakimov, D. S., Kocić, G.,& Šmelcerović, A.. (2021). 1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors. in Chemistry and Biodisversity
Wiley., 18(8), e2100261.
https://doi.org/10.1002/cbdv.202100261

Gajić M, Ilić BS, Bondžić B, Džambaski Z, Kojić VV, Jakimov DS, Kocić G, Šmelcerović A. 1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors. in Chemistry and Biodisversity. 2021;18(8):e2100261.
doi:10.1002/cbdv.202100261 .

Gajić, Mihajlo, Ilić, Budimir S., Bondžić, Bojan, Džambaski, Zdravko, Kojić, Vesna V., Jakimov, Dimitar S., Kocić, Gordana, Šmelcerović, Andrija, "1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors" in Chemistry and Biodisversity, 18, no. 8 (2021):e2100261,
https://doi.org/10.1002/cbdv.202100261 . .