SC-560 and mofezolac isosteres as new potent COX-1 selective inhibitors with antiplatelet effect
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F23%3A00570616" target="_blank" >RIV/61389030:_____/23:00570616 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11160/23:10470932
Result on the web
<a href="https://doi.org/10.1002/ardp.202200549" target="_blank" >https://doi.org/10.1002/ardp.202200549</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/ardp.202200549" target="_blank" >10.1002/ardp.202200549</a>
Alternative languages
Result language
angličtina
Original language name
SC-560 and mofezolac isosteres as new potent COX-1 selective inhibitors with antiplatelet effect
Original language description
Selective cyclooxygenase (COX)-1 inhibitors can be employed as potential cardioprotective drugs. Moreover, COX-1 plays a key role in inflammatory processes and its activity is associated with some types of cancer. In this work, we designed and synthesized a set of compounds that structurally mimic the selective COX-1 inhibitors, SC-560 and mofezolac, the central cores of which were replaced either with triazole or benzene rings. The advantage of this approach is a relatively simple synthesis in comparison with the syntheses of parent compounds. The newly synthesized compounds exhibited remarkable activity and selectivity toward COX-1 in the enzymatic in vitro assay. The most potent compound, 10a (IC50 = 3 nM for COX-1 and 850 nM for COX-2), was as active as SC-560 (IC50 = 2.4 nM for COX-1 and 470 nM for COX-2) toward COX-1 and it was even more selective. The in vitro COX-1 enzymatic activity was further confirmed in the cell-based whole-blood antiplatelet assay, where three out of four selected compounds (10a,c,d, and 3b) exerted outstanding IC50 values in the nanomolar range (9–252 nM). Moreover, docking simulations were performed to reveal key interactions within the COX-1 binding pocket. Furthermore, the toxicity of the selected compounds was tested using the normal human kidney HK-2 cell line.
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
10401 - Organic chemistry
Result continuities
Project
<a href="/en/project/LTC18065" target="_blank" >LTC18065: Selective COX-1 inhibition as cardioprotective therapeutical target</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Archiv der Pharmazie
ISSN
0365-6233
e-ISSN
1521-4184
Volume of the periodical
356
Issue of the periodical within the volume
5
Country of publishing house
DE - GERMANY
Number of pages
12
Pages from-to
e2200549
UT code for WoS article
000932685300001
EID of the result in the Scopus database
2-s2.0-85147937585