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Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent

INTRODUCTION: The gasotransmitter hydrogen sulphide (H(2)S), an endogenous ubiquitous signalling molecule, is known for its beneficial effects on different mammalian systems. H(2)S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury. METHODS: A library of forty-fi...

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Autores principales: Citi, Valentina, Corvino, Angela, Fiorino, Ferdinando, Frecentese, Francesco, Magli, Elisa, Perissutti, Elisa, Santagada, Vincenzo, Brogi, Simone, Flori, Lorenzo, Gorica, Era, Testai, Lara, Martelli, Alma, Calderone, Vincenzo, Caliendo, Giuseppe, Severino, Beatrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728584/
https://www.ncbi.nlm.nih.gov/pubmed/33318865
http://dx.doi.org/10.1016/j.jare.2020.02.017
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author Citi, Valentina
Corvino, Angela
Fiorino, Ferdinando
Frecentese, Francesco
Magli, Elisa
Perissutti, Elisa
Santagada, Vincenzo
Brogi, Simone
Flori, Lorenzo
Gorica, Era
Testai, Lara
Martelli, Alma
Calderone, Vincenzo
Caliendo, Giuseppe
Severino, Beatrice
author_facet Citi, Valentina
Corvino, Angela
Fiorino, Ferdinando
Frecentese, Francesco
Magli, Elisa
Perissutti, Elisa
Santagada, Vincenzo
Brogi, Simone
Flori, Lorenzo
Gorica, Era
Testai, Lara
Martelli, Alma
Calderone, Vincenzo
Caliendo, Giuseppe
Severino, Beatrice
author_sort Citi, Valentina
collection PubMed
description INTRODUCTION: The gasotransmitter hydrogen sulphide (H(2)S), an endogenous ubiquitous signalling molecule, is known for its beneficial effects on different mammalian systems. H(2)S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury. METHODS: A library of forty-five isothiocyanates, selected for their different chemical properties, has been evaluated for its hydrogen sulfide (H(2)S) releasing capacity. The obtained results allowed to correlate several factors such as steric hindrance, electronic effects and position of the substituents to the observed H(2)S production. Moreover, the chemical-physical profiles of the selected compounds have been studied by an in silico approach and from a combination of the obtained results, 3-pyridyl-isothiocyanate (25) has been selected as the most promising one. A detailed pharmacological characterization of its cardioprotective action has been performed. RESULTS: The results herein obtained strongly indicate 3-pyridyl-isothiocyanate (25) as a suitable pharmacological option in anti-ischemic therapy. The cardioprotective effects of compound 25 were tested in vivo and found to exhibit a positive effect. CONCLUSION: Results strongly suggest that isothiocyanate-based H(2)S-releasing drugs, such as compound 25, can trigger a ‘‘pharmacological pre-conditioning” and could represent a suitable pharmacological option in antiischemic therapy.
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spelling pubmed-77285842020-12-13 Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent Citi, Valentina Corvino, Angela Fiorino, Ferdinando Frecentese, Francesco Magli, Elisa Perissutti, Elisa Santagada, Vincenzo Brogi, Simone Flori, Lorenzo Gorica, Era Testai, Lara Martelli, Alma Calderone, Vincenzo Caliendo, Giuseppe Severino, Beatrice J Adv Res Article INTRODUCTION: The gasotransmitter hydrogen sulphide (H(2)S), an endogenous ubiquitous signalling molecule, is known for its beneficial effects on different mammalian systems. H(2)S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury. METHODS: A library of forty-five isothiocyanates, selected for their different chemical properties, has been evaluated for its hydrogen sulfide (H(2)S) releasing capacity. The obtained results allowed to correlate several factors such as steric hindrance, electronic effects and position of the substituents to the observed H(2)S production. Moreover, the chemical-physical profiles of the selected compounds have been studied by an in silico approach and from a combination of the obtained results, 3-pyridyl-isothiocyanate (25) has been selected as the most promising one. A detailed pharmacological characterization of its cardioprotective action has been performed. RESULTS: The results herein obtained strongly indicate 3-pyridyl-isothiocyanate (25) as a suitable pharmacological option in anti-ischemic therapy. The cardioprotective effects of compound 25 were tested in vivo and found to exhibit a positive effect. CONCLUSION: Results strongly suggest that isothiocyanate-based H(2)S-releasing drugs, such as compound 25, can trigger a ‘‘pharmacological pre-conditioning” and could represent a suitable pharmacological option in antiischemic therapy. Elsevier 2020-03-03 /pmc/articles/PMC7728584/ /pubmed/33318865 http://dx.doi.org/10.1016/j.jare.2020.02.017 Text en © 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Citi, Valentina
Corvino, Angela
Fiorino, Ferdinando
Frecentese, Francesco
Magli, Elisa
Perissutti, Elisa
Santagada, Vincenzo
Brogi, Simone
Flori, Lorenzo
Gorica, Era
Testai, Lara
Martelli, Alma
Calderone, Vincenzo
Caliendo, Giuseppe
Severino, Beatrice
Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent
title Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent
title_full Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent
title_fullStr Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent
title_full_unstemmed Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent
title_short Structure-activity relationships study of isothiocyanates for H(2)S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent
title_sort structure-activity relationships study of isothiocyanates for h(2)s releasing properties: 3-pyridyl-isothiocyanate as a new promising cardioprotective agent
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728584/
https://www.ncbi.nlm.nih.gov/pubmed/33318865
http://dx.doi.org/10.1016/j.jare.2020.02.017
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