Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives

Abstract A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. The antioxidant activity of all derivatives was investigated by three in vitro antioxidant assays, and the derivative with pyrrolidinedithiocarbamate moiety was the most active as a ra...

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Autores principales:	Beata Jasiewicz, Weronika Kozanecka-Okupnik, Michał Przygodzki, Beata Warżajtis, Urszula Rychlewska, Tomasz Pospieszny, Lucyna Mrówczyńska
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/017779a06b6b4985a8841ab1b91cf341
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spelling	oai:doaj.org-article:017779a06b6b4985a8841ab1b91cf3412021-12-02T16:30:10ZSynthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives10.1038/s41598-021-94904-z2045-2322https://doaj.org/article/017779a06b6b4985a8841ab1b91cf3412021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94904-zhttps://doaj.org/toc/2045-2322Abstract A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. The antioxidant activity of all derivatives was investigated by three in vitro antioxidant assays, and the derivative with pyrrolidinedithiocarbamate moiety was the most active as a radical scavenger and Fe3+-Fe2+ reducer. It can be stated that possible hydrogen and electron transfer mechanism is suggested for the quenching of the free radical. Moreover, the indolyl radical stabilization and the presence of unsubstituted indole nitrogen atom are mandatory for the observed antioxidant activity, which strongly depends on the type of the substituent directly connected to the methylene group at the C-3 position. Human red blood cells (RBC) have been used as a cell model to study derivatives interaction with the cell membrane. Haemolytic activity and RBC shape transformation were observed for certain derivatives in a concentration-dependent manner. However, most of the derivatives at sublytic concentration showed high cytoprotective activity against oxidative haemolysis induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The cytoprotective properties of derivatives can be explained mostly due to their interactions with the RBC membrane components. Taking together, theoretical estimations and experimental data confirm the beneficial interactions between the selected C-3 substituted indole derivatives and the RBC membrane under oxidative stress conditions. These results encourage us to further structural optimization of C-3 substituted indole derivatives as potent antioxidant compounds.Beata JasiewiczWeronika Kozanecka-OkupnikMichał PrzygodzkiBeata WarżajtisUrszula RychlewskaTomasz PospiesznyLucyna MrówczyńskaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beata Jasiewicz Weronika Kozanecka-Okupnik Michał Przygodzki Beata Warżajtis Urszula Rychlewska Tomasz Pospieszny Lucyna Mrówczyńska Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives
description	Abstract A series of fifteen indole derivatives substituted at the C-3 position were synthesized and characterized. The antioxidant activity of all derivatives was investigated by three in vitro antioxidant assays, and the derivative with pyrrolidinedithiocarbamate moiety was the most active as a radical scavenger and Fe3+-Fe2+ reducer. It can be stated that possible hydrogen and electron transfer mechanism is suggested for the quenching of the free radical. Moreover, the indolyl radical stabilization and the presence of unsubstituted indole nitrogen atom are mandatory for the observed antioxidant activity, which strongly depends on the type of the substituent directly connected to the methylene group at the C-3 position. Human red blood cells (RBC) have been used as a cell model to study derivatives interaction with the cell membrane. Haemolytic activity and RBC shape transformation were observed for certain derivatives in a concentration-dependent manner. However, most of the derivatives at sublytic concentration showed high cytoprotective activity against oxidative haemolysis induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The cytoprotective properties of derivatives can be explained mostly due to their interactions with the RBC membrane components. Taking together, theoretical estimations and experimental data confirm the beneficial interactions between the selected C-3 substituted indole derivatives and the RBC membrane under oxidative stress conditions. These results encourage us to further structural optimization of C-3 substituted indole derivatives as potent antioxidant compounds.
format	article
author	Beata Jasiewicz Weronika Kozanecka-Okupnik Michał Przygodzki Beata Warżajtis Urszula Rychlewska Tomasz Pospieszny Lucyna Mrówczyńska
author_facet	Beata Jasiewicz Weronika Kozanecka-Okupnik Michał Przygodzki Beata Warżajtis Urszula Rychlewska Tomasz Pospieszny Lucyna Mrówczyńska
author_sort	Beata Jasiewicz
title	Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives
title_short	Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives
title_full	Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives
title_fullStr	Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives
title_full_unstemmed	Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives
title_sort	synthesis, antioxidant and cytoprotective activity evaluation of c-3 substituted indole derivatives
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/017779a06b6b4985a8841ab1b91cf341
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Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives

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