Identification of Novel Aldose Reductase Inhibitors Based on Carboxymethylated Mercaptotriazinoindole Scaffold

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 excellent “leadlikeness” of 13 as a
promising candidate for further structure optimizations.