Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity

A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell’s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic...

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Autores principales: Krasavin, Mikhail, Sharonova, Tatiana, Sharoyko, Vladimir, Zhukovsky, Daniil, Kalinin, Stanislav, Žalubovskis, Raivis, Tennikova, Tatiana, Supuran, Claudiu T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Short Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067156/
https://www.ncbi.nlm.nih.gov/pubmed/32131646
http://dx.doi.org/10.1080/14756366.2020.1734800
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author Krasavin, Mikhail
Sharonova, Tatiana
Sharoyko, Vladimir
Zhukovsky, Daniil
Kalinin, Stanislav
Žalubovskis, Raivis
Tennikova, Tatiana
Supuran, Claudiu T.
author_facet Krasavin, Mikhail
Sharonova, Tatiana
Sharoyko, Vladimir
Zhukovsky, Daniil
Kalinin, Stanislav
Žalubovskis, Raivis
Tennikova, Tatiana
Supuran, Claudiu T.
author_sort Krasavin, Mikhail
collection PubMed
description A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell’s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.
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spelling pubmed-70671562020-03-19 Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity Krasavin, Mikhail Sharonova, Tatiana Sharoyko, Vladimir Zhukovsky, Daniil Kalinin, Stanislav Žalubovskis, Raivis Tennikova, Tatiana Supuran, Claudiu T. J Enzyme Inhib Med Chem Short Communication A hypothesis that simultaneous targeting cancer-related carbonic anhydrase hCA IX and hCA XII isoforms (whose overexpression is a cancer cell’s defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design. Taylor & Francis 2020-03-05 /pmc/articles/PMC7067156/ /pubmed/32131646 http://dx.doi.org/10.1080/14756366.2020.1734800 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Krasavin, Mikhail
Sharonova, Tatiana
Sharoyko, Vladimir
Zhukovsky, Daniil
Kalinin, Stanislav
Žalubovskis, Raivis
Tennikova, Tatiana
Supuran, Claudiu T.
Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
title Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
title_full Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
title_fullStr Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
title_full_unstemmed Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
title_short Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
title_sort combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067156/
https://www.ncbi.nlm.nih.gov/pubmed/32131646
http://dx.doi.org/10.1080/14756366.2020.1734800
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