Discovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibition
Ημερομηνία
2016Συγγραφέας
Sweeney, M.Coyle, R.
Kavanagh, P.
Berezin, Andrey A.
Lo Re, D.
![ORCID logo](https://orcid.org/sites/default/files/images/orcid_16x16.png)
![ORCID logo](https://orcid.org/sites/default/files/images/orcid_16x16.png)
Carty, Michael P.
Aldabbagh, Fawaz
Source
Bioorganic and Medicinal ChemistryVolume
24Issue
16Pages
3565-3570Google Scholar check
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Εμφάνιση πλήρους εγγραφήςΕπιτομή
The thioredoxin (Trx)–thioredoxin reductase (TrxR) system plays a key role in maintaining the cellular redox balance with Trx being over-expressed in a number of cancers. Inhibition of TrxR is an important strategy for anti-cancer drug discovery. The natural product pleurotin is a well-known irreversible inhibitor of TrxR. The cytotoxicity data for benzo[1,2,4]triazin-7-ones showed very strong correlation (Pearson correlation coefficients ∼0.8) to pleurotin using National Cancer Institute COMPARE analysis. A new 3-CF3substituted benzo[1,2,4]triazin-7-one gave submicromolar inhibition of TrxR, although the parent compound 1,3-diphenylbenzo[1,2,4]triazin-7-one was more cytotoxic against cancer cell lines. Benzo[1,2,4]triazin-7-ones exhibited different types of reversible inhibition of TrxR, and cyclic voltammetry showed characteristic quasi-reversible redox processes. Cell viability studies indicated strong dependence of cytotoxicity on substitution at the 6-position of the 1,3-diphenylbenzo[1,2,4]triazin-7-one ring. © 2016 Elsevier Ltd
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Discovery of anti-cancer activity for benzo1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibition
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