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

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 a...

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Veröffentlicht in:	Journal of enzyme inhibition and medicinal chemistry 2020-01, Vol.35 (1), p.506-510
Hauptverfasser:	Krasavin, Mikhail, Žalubovskis, Raivis, Grandāne, Aiga, Domračeva, Ilona, Zhmurov, Petr, Supuran, Claudiu T.
Format:	Artikel
Sprache:	eng
Schlagworte:	Anticancer agents Antigens, Neoplasm - metabolism Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biochemistry & Molecular Biology Cancer carbonic anhydrase inhibition Carbonic Anhydrase IX - antagonists & inhibitors Carbonic Anhydrase IX - metabolism Carbonic anhydrases Carbonic Anhydrases - metabolism Cell Proliferation - drug effects Cell Survival - drug effects Chemistry, Medicinal Coumarins - chemical synthesis Coumarins - chemistry Coumarins - pharmacology Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Humans Hypoxia Isoenzymes - antagonists & inhibitors Isoenzymes - metabolism Isoforms Life Sciences & Biomedicine MCF-7 Cells Medical innovations Molecular Structure Oxidative stress Pharmacology & Pharmacy Rapid Communication Science & Technology Short Communication Structure-Activity Relationship Thioredoxin thioredoxin reductase inhibition Thioredoxin-Disulfide Reductase - antagonists & inhibitors Thioredoxin-Disulfide Reductase - metabolism Tumor cell lines Tumor Cells, Cultured
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Zusammenfassung:	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.
ISSN:	1475-6366 1475-6374
DOI:	10.1080/14756366.2020.1712596