Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity
Mikhail Krasavin, Tatiana V. Sharonova, Vladimir V. Sharoyko, Daniil Zhukovsky, Stanislav Kalinin, Raivis Žalubovskis, Tatiana Tennikova, Claudiu T. Supuran
Abstract
CA 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.
Topics & Concepts
Thioredoxin reductaseCytotoxicityCarbonic anhydraseThioredoxinChemistryBiochemistryEnzymeCancer cellGene isoformSmall moleculeCancerBiologyIn vitroGeneGeneticsEnzyme function and inhibitionSynthesis and Catalytic ReactionsCholinesterase and Neurodegenerative Diseases