Collagenase inhibitors from Viola yedoensis

Fractionation of acetone and methanol extracts of Viola yedoensis, under the guidance of inhibition against Clostridium histolyticum collagenase (ChC), resulted in the isolation of esculetin (1) (IC₅₀ 12 μM) and scopoletin (2) (IC₅₀ 1.8 μM) as the active constituents, together with trans-p-coumaric acid (3), cis-p-coumaric acid (4), 3-O-β-d-glucosyl- 7-O-α-L-rhamnosylkaempferol (5), rutin (6), isovitexin (7), isoorientin (8), vicenin-2 (9), isoscoparin (10), vanillic acid (11) and adenosine (12). Modification of phenolic hydroxy groups of 1 showed that small O-alkyl groups largely increased the activity, whereas larger O-alkyl groups decreased the activity, and 6,7-dimethoxycoumarin (scoparone 13) potently inhibited ChC (IC₅₀ 24 nM).