Drug-like Inhibitors of DC-SIGN Based on a Quinolone Scaffold

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F22%3A43924231" target="_blank" >RIV/60461373:22310/22:43924231 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/22:73615723 RIV/61989592:15310/22:73615723
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acsmedchemlett.2c00067" target="_blank" >https://pubs.acs.org/doi/10.1021/acsmedchemlett.2c00067</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsmedchemlett.2c00067" target="_blank" >10.1021/acsmedchemlett.2c00067</a>

Result language
angličtina
Original language name
Drug-like Inhibitors of DC-SIGN Based on a Quinolone Scaffold
Original language description
DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) is a pattern recognition receptor expressed on immune cells and involved in the recognition of carbohydrate signatures present on various pathogens, including HIV, Ebola, and SARS-CoV-2. Therefore, developing inhibitors blocking the carbohydrate-binding site of DC-SIGN could generate a valuable tool to investigate the role of this receptor in several infectious diseases. Herein, we performed a fragment-based ligand design using 4-quinolone as a scaffold. We synthesized a library of 61 compounds, performed a screening against DC-SIGN using an STD reporter assay, and validated these data using protein-based 1H-15N HSQC NMR. Based on the structure-activity relationship data, we demonstrate that ethoxycarbonyl or dimethylaminocarbonyl in position 2 or 3 is favorable for the DC-SIGN binding activity, especially in combination with fluorine, ethoxycarbonyl, or dimethylaminocarbonyl in position 7 or 8. Furthermore, we demonstrate that these quinolones can allosterically modulate the carbohydrate binding site, which offers an alternative approach toward this challenging protein target. © 2022 American Chemical Society. All rights reserved.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10401 - Organic chemistry

Project
<a href="/en/project/GJ18-26557Y" target="_blank" >GJ18-26557Y: 3-Hydroxyquinolin-4(1H)-ones as biologically interesting molecules</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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