1,2,3,4‐Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors
| Autor: | Dimitar Jakimov, Zdravko Džambaski, Andrija Smelcerovic, Vesna Kojić, Bojan P. Bondžić, Budimir S. Ilić, Gordana Kocic, Mihajlo Gajić |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Tetrahydroisoquinoline derivatives
Apoptosis DNase I Bioengineering Molecular Dynamics Simulation Inhibitory postsynaptic potential Biochemistry Cell Line Inhibitory Concentration 50 Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Catalytic Domain Tetrahydroisoquinolines Ic50 values Deoxyribonuclease I Humans Enzyme Inhibitors Cytotoxicity enzyme inhibition Molecular Biology IC50 030304 developmental biology 0303 health sciences Binding Sites Chemistry molecular docking General Chemistry General Medicine molecular dynamics 3. Good health Molecular Docking Simulation Cell culture 030220 oncology & carcinogenesis Apoptotic cell death Molecular Medicine |
| Zdroj: | Chemistry and Biodisversity |
| ISSN: | 1612-1880 1612-1872 |
| DOI: | 10.1002/cbdv.202100261 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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