Discovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibition
Berezin, Andrey A.
Lo Re, D.
Zissimou, Georgia A.
Koutentis, Panayiotis Andreas
Carty, Michael P.
SourceBioorganic and Medicinal Chemistry
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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 Sweeney, Martin; Coyle, Robert; Kavanagh, Paul; Berezin, Andrey A.; Lo Re, Daniele; Zissimou, Georgia A.; Koutentis, Panayiotis Andreas; Carty, Michael P.; Aldabbagh, Fawaz (2016)