• Something wrong with this record ?

Screening of Synthetic Heterocyclic Compounds as Antiplatelet Drugs

M. Hrubša, K. Nurjamal, A. Carazo, N. Nayek, J. Karlíčková, L. Applová, I. Karmakar, S. Parvin, J. Fadraersada, K. Macáková, P. Mladěnka, G. Brahmachari

. 2022 ; 18 (5) : 536-543. [pub] -

Language English Country Netherlands

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc22019558

Grant support
CZ.02.1.01/0.0/0.0/16_019/0000841 EFSA-CDN project
SVV 260 549 Charles University

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22019558
003      
CZ-PrNML
005      
20221018084754.0
007      
ta
008      
220720s2022 ne f 000 0|eng||
009      
AR
024    7_
$a 10.2174/1573406417666211026150658 $2 doi
035    __
$a (PubMed)34702153
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Hrubša, Marcel $u Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
245    10
$a Screening of Synthetic Heterocyclic Compounds as Antiplatelet Drugs / $c M. Hrubša, K. Nurjamal, A. Carazo, N. Nayek, J. Karlíčková, L. Applová, I. Karmakar, S. Parvin, J. Fadraersada, K. Macáková, P. Mladěnka, G. Brahmachari
520    9_
$a 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.
650    _2
$a Aspirin $x farmakologie $7 D001241
650    _2
$a trombocyty $7 D001792
650    12
$a heterocyklické sloučeniny $x farmakologie $7 D006571
650    _2
$a lidé $7 D006801
650    _2
$a agregace trombocytů $7 D010974
650    12
$a inhibitory agregace trombocytů $x farmakologie $7 D010975
655    _2
$a časopisecké články $7 D016428
700    1_
$a Nurjamal, Khondekar $u Department of Chemistry, Visva-Bharati (Central University), Santiniketan, India
700    1_
$a Carazo, Alejandro $u Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
700    1_
$a Nayek, Nayana $u Department of Chemistry, Visva-Bharati (Central University), Santiniketan, India
700    1_
$a Karlíčková, Jana $u Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
700    1_
$a Applová, Lenka $u Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic $7 xx0277670
700    1_
$a Karmakar, Indrajit $u Department of Chemistry, Visva-Bharati (Central University), Santiniketan, India
700    1_
$a Parvin, Shamima $u Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
700    1_
$a Fadraersada, Jaka $u Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
700    1_
$a Macáková, Kateřina $u Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
700    1_
$a Mladěnka, Přemysl $u Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
700    1_
$a Brahmachari, Goutam $u Department of Pharmacognosy, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
773    0_
$w MED00180387 $t Medicinal chemistry $x 1875-6638 $g Roč. 18, č. 5 (2022), s. 536-543
856    41
$u https://pubmed.ncbi.nlm.nih.gov/34702153 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220720 $b ABA008
991    __
$a 20221018084751 $b ABA008
999    __
$a ok $b bmc $g 1822958 $s 1170801
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 18 $c 5 $d 536-543 $e - $i 1875-6638 $m Medicinal chemistry $n Med Chem $x MED00180387
GRA    __
$a CZ.02.1.01/0.0/0.0/16_019/0000841 $p EFSA-CDN project
GRA    __
$a SVV 260 549 $p Charles University
LZP    __
$a Pubmed-20220720

Find record

Citation metrics

Archiving options