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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Detalles Bibliográficos
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
Descripción
Sumario: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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