Sulfocoumarins as dual inhibitors of human carbonic anhydrase isoforms IX/XII and of human thioredoxin reductase
Mikhail Krasavin, Raivis Žalubovskis, Aiga Grandāne, Ilona Domračeva, Petr A. Zhmurov, Claudiu T. Supuran
Abstract
The hypothesis that sulfocoumarin acting as inhibitors of human carbonic anhydrase (CA, EC 4.2.1.1) cancer-associated isoforms hCA IX and – hCA XII is being able to also inhibit thioredoxin reductase was verified and confirmed. The dual targeting of two cancer cell defence mechanisms, i.e. hypoxia and oxidative stress, may both contribute to the observed antiproliferative profile of these compounds against many cancer cell lines. This unprecedented dual anticancer mechanism may lead to a new approach for designing innovative therapeutic agents.
Topics & Concepts
Thioredoxin reductaseThioredoxinGene isoformCarbonic anhydraseEnzymeCancer cellBiochemistryDual roleChemistryReductaseCancerBiologyCombinatorial chemistryGeneGeneticsEnzyme function and inhibitionSynthesis and Catalytic ReactionsChemical Reactions and Mechanisms