Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Notes
Trivaric Acid, a Potent Depside Human Leukocyte Elastase Inhibitor
Zhihui ZhengShen ZhangXinhua LuYing MaYuling FanYing ShiAihua DongBaoling Duan
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2012 Volume 35 Issue 12 Pages 2247-2251

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Abstract

Human leukocyte elastase (HLE) is a serine protease implicated in several inflammatory diseases, and represents a major target for anti-inflammatory drug development. In the present study, nordivaricatic acid (1), divarinyl divarate (2), and trivaric acid (3), three depsides isolated from the culture of a soil derived fungal strain were identified as inhibitors of HLE. Two didepsides 1 and 2 showed low inhibitory activity. In contrast, trivaric acid, a para-tridepside, exhibited highly potent inhibitory activity with an IC50 value of 1.8 µM and a Ki of 0.6 µM. Kinetic investigations with trivaric acid showed that this inhibition is reversible, competitive pattern. Further studies on the selectivity of three depsides toward serine proteases showed that they did not inhibit chymotrypsin, trypsin and thrombin even at 150 µM.

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© 2012 The Pharmaceutical Society of Japan
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