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Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents

Prodigiosin is one of the most potent anion transporters in lipid bilayer membranes reported to date. Inspired by the structure of this natural product, we have recently designed and synthesised a new class of H(+)/Cl(−) cotransporters named ‘perenosins’. Here we report a new library of indole-based...

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Autores principales: Jowett, Laura A., Howe, Ethan N. W., Soto-Cerrato, Vanessa, Van Rossom, Wim, Pérez-Tomás, Ricardo, Gale, Philip A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570892/
https://www.ncbi.nlm.nih.gov/pubmed/28839192
http://dx.doi.org/10.1038/s41598-017-09645-9
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author Jowett, Laura A.
Howe, Ethan N. W.
Soto-Cerrato, Vanessa
Van Rossom, Wim
Pérez-Tomás, Ricardo
Gale, Philip A.
author_facet Jowett, Laura A.
Howe, Ethan N. W.
Soto-Cerrato, Vanessa
Van Rossom, Wim
Pérez-Tomás, Ricardo
Gale, Philip A.
author_sort Jowett, Laura A.
collection PubMed
description Prodigiosin is one of the most potent anion transporters in lipid bilayer membranes reported to date. Inspired by the structure of this natural product, we have recently designed and synthesised a new class of H(+)/Cl(−) cotransporters named ‘perenosins’. Here we report a new library of indole-based perenosins and their anion transport properties. The new transporters demonstrated superior transmembrane transport efficiency when compared to other indole-based transporters, due to favourable encapsulating effects from the substituents on the perenosin backbone. Anion transport assays were used to determine the mechanism of chloride transport revealing that the compounds function as ‘strict’ HCl cotransporters. Cell viability studies showed that some compounds specifically trigger late-onset cell death after 72 h with a unique correlation to the position of alkyl chains on the perenosins. Further investigations of cell death mechanism showed a mixture of cell cycle arrest and apoptosis was responsible for the observed decrease in cell viability.
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spelling pubmed-55708922017-09-01 Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents Jowett, Laura A. Howe, Ethan N. W. Soto-Cerrato, Vanessa Van Rossom, Wim Pérez-Tomás, Ricardo Gale, Philip A. Sci Rep Article Prodigiosin is one of the most potent anion transporters in lipid bilayer membranes reported to date. Inspired by the structure of this natural product, we have recently designed and synthesised a new class of H(+)/Cl(−) cotransporters named ‘perenosins’. Here we report a new library of indole-based perenosins and their anion transport properties. The new transporters demonstrated superior transmembrane transport efficiency when compared to other indole-based transporters, due to favourable encapsulating effects from the substituents on the perenosin backbone. Anion transport assays were used to determine the mechanism of chloride transport revealing that the compounds function as ‘strict’ HCl cotransporters. Cell viability studies showed that some compounds specifically trigger late-onset cell death after 72 h with a unique correlation to the position of alkyl chains on the perenosins. Further investigations of cell death mechanism showed a mixture of cell cycle arrest and apoptosis was responsible for the observed decrease in cell viability. Nature Publishing Group UK 2017-08-24 /pmc/articles/PMC5570892/ /pubmed/28839192 http://dx.doi.org/10.1038/s41598-017-09645-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jowett, Laura A.
Howe, Ethan N. W.
Soto-Cerrato, Vanessa
Van Rossom, Wim
Pérez-Tomás, Ricardo
Gale, Philip A.
Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents
title Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents
title_full Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents
title_fullStr Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents
title_full_unstemmed Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents
title_short Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents
title_sort indole-based perenosins as highly potent hcl transporters and potential anti-cancer agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570892/
https://www.ncbi.nlm.nih.gov/pubmed/28839192
http://dx.doi.org/10.1038/s41598-017-09645-9
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