Abstract Many triterpenoids have shown ability to inhibit hydrolyzing activity of angiotensin-converting enzyme; however, there has been no report about the structure-activity relationship and inhibition patterns of these compounds. In this study, 32 lanostane-type triterpenoids derived from Ganoderma lingzhi were assayed to determine the structural features involved in the observed inhibition effects. In silico and in vitro experiments were also used to determine the kinetics of the reaction. Fifteen compounds showed measurable in vitro IC50 values ranging from 0.194 to 0.941 mM. It was shown that carboxyl groups play an important role in inhibiting the enzyme; further, a hydroxyl group or carbonyl group at either C7 or C15 increases the inhibition rate, and a double bond at C24,25 decreases the activity. Based on the docking data we speculated that triterpenoids could not fit into the active site of the enzyme; therefore, the inhibition mode could not be competitive. Dixon plotting showed that the inhibition patterns should be uncompetitive and non-competitive instead.
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