Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases

Small drug-like molecules that can block the function of serotonin 5-HT2A receptors have garnered considerable attention due to their ability to inhibit platelet aggregation and the possible prevention of atherosclerotic lesions. Although clinical data provided compelling evidence for the efficacy o...

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Autores principales:	Monika Marcinkowska, Monika Kubacka, Agnieszka Zagorska, Anna Jaromin, Nikola Fajkis-Zajaczkowska, Marcin Kolaczkowski
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	5-HT2A receptor antagonist Antiplatelet agents 6-fluorobenzo[d]isoxazole derivatives Cardiovascular research Sarpogrelate Ketanserin Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0bb8cee8aad04c15b6bfe085a004d6ad
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spelling	oai:doaj.org-article:0bb8cee8aad04c15b6bfe085a004d6ad2021-11-14T04:30:36ZExploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases0753-332210.1016/j.biopha.2021.112424https://doaj.org/article/0bb8cee8aad04c15b6bfe085a004d6ad2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221012105https://doaj.org/toc/0753-3322Small drug-like molecules that can block the function of serotonin 5-HT2A receptors have garnered considerable attention due to their ability to inhibit platelet aggregation and the possible prevention of atherosclerotic lesions. Although clinical data provided compelling evidence for the efficacy of this approach in the prevention of various cardiovascular conditions, the chemical space of 5-HT2A receptor antagonists is limited to ketanserin and sarpogrelate. To expand the portfolio of novel chemical motifs with potential antiplatelet activity, we evaluated the antiplatelet activity of a series of 6-fluorobenzo[d]isoxazole derivatives that possess a high affinity for 5-HT2A receptor. Here we describe in vitro studies showing that 6-fluorobenzo[d]isoxazole derivatives exert promising antiplatelet activity in three various in vitro models of platelet aggregation, as well as limit serotonin-induced vasoconstriction. Compound AZ928 showed in vitro activity greater than the clinically approved drug sarpogrelate. In addition to promising antiplatelet activity, the novel series was characterized by a favorable safety profile. Our findings show that the novel series exerts promising antiplatelet efficacy while being deprived of potential side effects, such as hemolytic activity, which render these compounds as potential substances for further investigation in the field of cardiovascular research.Monika MarcinkowskaMonika KubackaAgnieszka ZagorskaAnna JarominNikola Fajkis-ZajaczkowskaMarcin KolaczkowskiElsevierarticle5-HT2A receptor antagonistAntiplatelet agents6-fluorobenzo[d]isoxazole derivativesCardiovascular researchSarpogrelateKetanserinTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112424- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	5-HT2A receptor antagonist Antiplatelet agents 6-fluorobenzo[d]isoxazole derivatives Cardiovascular research Sarpogrelate Ketanserin Therapeutics. Pharmacology RM1-950
spellingShingle	5-HT2A receptor antagonist Antiplatelet agents 6-fluorobenzo[d]isoxazole derivatives Cardiovascular research Sarpogrelate Ketanserin Therapeutics. Pharmacology RM1-950 Monika Marcinkowska Monika Kubacka Agnieszka Zagorska Anna Jaromin Nikola Fajkis-Zajaczkowska Marcin Kolaczkowski Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases
description	Small drug-like molecules that can block the function of serotonin 5-HT2A receptors have garnered considerable attention due to their ability to inhibit platelet aggregation and the possible prevention of atherosclerotic lesions. Although clinical data provided compelling evidence for the efficacy of this approach in the prevention of various cardiovascular conditions, the chemical space of 5-HT2A receptor antagonists is limited to ketanserin and sarpogrelate. To expand the portfolio of novel chemical motifs with potential antiplatelet activity, we evaluated the antiplatelet activity of a series of 6-fluorobenzo[d]isoxazole derivatives that possess a high affinity for 5-HT2A receptor. Here we describe in vitro studies showing that 6-fluorobenzo[d]isoxazole derivatives exert promising antiplatelet activity in three various in vitro models of platelet aggregation, as well as limit serotonin-induced vasoconstriction. Compound AZ928 showed in vitro activity greater than the clinically approved drug sarpogrelate. In addition to promising antiplatelet activity, the novel series was characterized by a favorable safety profile. Our findings show that the novel series exerts promising antiplatelet efficacy while being deprived of potential side effects, such as hemolytic activity, which render these compounds as potential substances for further investigation in the field of cardiovascular research.
format	article
author	Monika Marcinkowska Monika Kubacka Agnieszka Zagorska Anna Jaromin Nikola Fajkis-Zajaczkowska Marcin Kolaczkowski
author_facet	Monika Marcinkowska Monika Kubacka Agnieszka Zagorska Anna Jaromin Nikola Fajkis-Zajaczkowska Marcin Kolaczkowski
author_sort	Monika Marcinkowska
title	Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases
title_short	Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases
title_full	Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases
title_fullStr	Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases
title_full_unstemmed	Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases
title_sort	exploring the antiplatelet activity of serotonin 5-ht2a receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/0bb8cee8aad04c15b6bfe085a004d6ad
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Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif– as potential therapeutic agents in the prevention of cardiovascular diseases

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