Inhibition of serine proteases by anti-inflammatory triterpenoids

The lupane triterpenoid lupeol, the ursane triterpenoid alpha-amyrin and es ters of these compounds are present in the bark of roots of Alstonia boonei (Apocynaceae) and have anti-inflammatory properties. alpha-Amyrin is a com petitive inhibitor of bovine trypsin and chymotrypsin (K-i values 29 mu M a nd 18 mu M, respectively). Lupeol linoleate, lupeol palmitate and alpha-amy rin linoleate are non-competitive inhibitors of trypsin (Ki values 7 mu M, 10 mu M and 16 mu M, respectively). alpha-Amyrin linoleate is also a non-co mpetitive inhibitor of chymotrypsin (Ki value 28 mu M). Lupeol is a competi tive inhibitor of both trypsin and chymotrypsin (K-i values 22 and 8 mu M, respectively). alpha-Amyrin palmitate is a potent non-competitive inhibitor of chymotrypsin (K-i 6 mu M). Lupeol, alpha-amyrin and the palmitic and li noleic acid esters of these compounds are ineffective or very weak as inhib itors of porcine pancreatic elastase and of Lucilia cuprina and Helicoverpa punctigera leucine aminopeptidases. These hydrophobic triterpenoids repres ent further examples of anti-inflammatory triterpenoids that are PKA inhibi tors as well as being selective protease inhibitors.