Screening of Synthetic Heterocyclic Compounds as Antiplatelet Drugs
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F22%3A10443795" target="_blank" >RIV/00216208:11160/22:10443795 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jjlUegFnBM" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jjlUegFnBM</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.2174/1573406417666211026150658" target="_blank" >10.2174/1573406417666211026150658</a>
Alternative languages
Result language
angličtina
Original language name
Screening of Synthetic Heterocyclic Compounds as Antiplatelet Drugs
Original language description
Background: Antiplatelet drugs represent the keystone in the treatment and prevention of diseases of ischemic origin, including coronary artery disease. The current palette of drugs represents efficient modalities in most cases, but their effect can be limited in certain situations or associated with specific side effects. In this study, representatives of compounds selected from series having scaffolds with known or potential antiplatelet activity were tested. These compounds were previously synthetized by us, but their biological effects have not yet been reported. Objective: The aim of this study was to examine the antiplatelet and anticoagulation properties of selected compounds and determine their mechanism of action. Methods: Antiplatelet activity of compounds and their mechanisms of action were evaluated using human blood by impedance aggregometry and various aggregation inducers and inhibitors and compared to appropriate standards. Cytotoxicity was tested using breast adenocarcinoma cell cultures and potential anticoagulation activity was also determined. Results: In total, four of 34 compounds tested were equally or more active than the standard antiplatelet drug Acetylsalicylic Acid (ASA). In contrast to ASA, all 4 active compounds decreased platelet aggregation triggered not only by collagen, but also partly by ADP. The major mechanism of action is based on antagonism at thromboxane receptors. In higher concentrations, inhibition of thromboxane synthase was also noted. In contrast to ASA, the tested compounds did not block cyclooxygenase-1. Conclusion: The most active compound, 2-amino-4-(1H-indol-3-yl)-6-nitro-4H-chromene-3-carbonitrile (2-N), which is 4-5x times more potent than ASA, is a promising compound for the development of novel antiplatelet drugs.
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
<a href="/en/project/EF16_019%2F0000841" target="_blank" >EF16_019/0000841: Efficiency and safety improvement of current drugs and nutraceuticals: advanced methods - new challenges</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
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
Medicinal Chemistry
ISSN
1573-4064
e-ISSN
1875-6638
Volume of the periodical
18
Issue of the periodical within the volume
5
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
8
Pages from-to
536-543
UT code for WoS article
000756598400002
EID of the result in the Scopus database
2-s2.0-85127486518