2015
DOI: 10.1021/jm5015814
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Identification of Novel Aldose Reductase Inhibitors Based on Carboxymethylated Mercaptotriazinoindole Scaffold

Abstract: Fifteen compounds, sharing an indole-1-acetic acid moiety as a common fragment, were selected from commercial databases for testing aldose reductase inhibition. 3-Mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (13) was the most promising inhibitor, with an IC50 in the submicromolar range and high selectivity, relative to aldehyde reductase. The crystal structure of aldose reductase complexed with 13 revealed an interaction pattern explaining its high affinity. Physicochemical parameters underline the ex… Show more

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Cited by 44 publications
(60 citation statements)
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“…Compound 1 belongs to a group of novel carboxymethylated mercapto-triazino-indole derivatives, recently projected as aldose reductase inhibitors. 39 The biological activity of 1 was characterized with an IC 50 in submicromolar range for aldose reductase inhibition and high selectivity in relation to congeneric aldo-keto reductases. In addition, physicochemical properties of 1 corresponding to excellent 'drug-likeness' render the compound a prospective agent with a therapeutic potential in the treatment of diabetic complications.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Compound 1 belongs to a group of novel carboxymethylated mercapto-triazino-indole derivatives, recently projected as aldose reductase inhibitors. 39 The biological activity of 1 was characterized with an IC 50 in submicromolar range for aldose reductase inhibition and high selectivity in relation to congeneric aldo-keto reductases. In addition, physicochemical properties of 1 corresponding to excellent 'drug-likeness' render the compound a prospective agent with a therapeutic potential in the treatment of diabetic complications.…”
Section: Discussionmentioning
confidence: 99%
“…This finding is in agreement with preferred thione tautomeric forms of 1 at neutral pH shown before. 39 Analogically, 2-mercaptopyrimidines, 44 substituted 1,2,4-triazole-3-thiones, 45 and the mercaptoimidazole derivative ergothioneine 46 exist in water solutions predominantly in the thione tautomer forms.…”
Section: Discussionmentioning
confidence: 99%
“…64 acid (CMTI) was characterized by a corresponding IC 50 value in a submicromolar region. A reasonable degree of selectivity with respect to the closely related aldehyde reductase and AKR1B10 oxidoreductase (Stefek et al 2015) was recorded.…”
mentioning
confidence: 85%
“…Recently novel carboxymethylated mercaptotriazinoindoles have been identified as efficient inhibitors of aldose reductase (Stefek et al 2015). Of them, 3-mercapto- 5H-1,2,4-triazino[5,6-b]indole-5-acetic Vol.…”
mentioning
confidence: 99%
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