Drug-like Inhibitors of DC-SIGN Based on a Quinolone Scaffold
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F22%3A73615723" target="_blank" >RIV/61989592:15110/22:73615723 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/22:73615723 RIV/60461373:22310/22:43924231
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>
Alternative languages
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 1 H−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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
—
Continuities
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Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Medicinal Chemistry Letters
ISSN
1948-5875
e-ISSN
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Volume of the periodical
13
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
935-942
UT code for WoS article
000810244600001
EID of the result in the Scopus database
2-s2.0-85130817816