Screening of Synthetic Heterocyclic Compounds as Antiplatelet Drugs
Language English Country Netherlands Media print
Document type Journal Article
Grant support
CZ.02.1.01/0.0/0.0/16_019/0000841
EFSA-CDN project
SVV 260 549
Charles University
PubMed
34702153
DOI
10.2174/1573406417666211026150658
PII: MC-EPUB-118568
Knihovny.cz E-resources
- Keywords
- Pyridopyrimidine, acridine, aggregation, coagulation, coumarin, indole,
- MeSH
- Platelet Aggregation MeSH
- Aspirin pharmacology MeSH
- Heterocyclic Compounds * pharmacology MeSH
- Platelet Aggregation Inhibitors * pharmacology MeSH
- Humans MeSH
- Blood Platelets MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Aspirin MeSH
- Heterocyclic Compounds * MeSH
- Platelet Aggregation Inhibitors * MeSH
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.
Department of Chemistry Visva Bharati Santiniketan India
Department of Pharmacognosy Faculty of Pharmacy Charles University Hradec Králové Czech Republic
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