Sulfocoumarins as dual inhibitors of human carbonic anhydrase isoforms IX/XII and of human thioredoxin reductase

Research output: Contribution to journal › Article › peer-review

Laboratory of Chemical Pharmacology

DOI

https://doi.org/10.1080/14756366.2020.1712596
Final published version

Mikhail Krasavin
Raivis Žalubovskis
Aiga Grandāne
Ilona Domračeva
Petr Zhmurov
Claudiu T. Supuran

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.

Original language	English
Pages (from-to)	506-510
Number of pages	5
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	35
Issue number	1
Early online date	2 Dec 2019
DOIs	https://doi.org/10.1080/14756366.2020.1712596
State	Published - 1 Jan 2020

Scopus subject areas

Drug Discovery
Pharmacology

Research areas

Anticancer agents, carbonic anhydrase inhibition, hypoxia, oxidative stress, thioredoxin reductase inhibition, Humans, Structure-Activity Relationship, Cell Survival/drug effects, Thioredoxin-Disulfide Reductase/antagonists & inhibitors, Coumarins/chemical synthesis, Antineoplastic Agents/chemical synthesis, Carbonic Anhydrase IX/antagonists & inhibitors, Dose-Response Relationship, Drug, MCF-7 Cells, Carbonic Anhydrases/metabolism, Molecular Structure, Cell Proliferation/drug effects, Isoenzymes/antagonists & inhibitors, Tumor Cells, Cultured, Enzyme Inhibitors/chemical synthesis, Antigens, Neoplasm/metabolism, Drug Screening Assays, Antitumor, SYSTEM, COUMARINS, IX, POTENT, BENZENESULFONAMIDES, SELECTIVE INHIBITORS

ID: 51052715