Structure-Activity Relationship of Pentacylic Triterpene Esters from Uncaria rhynchophylla as Inhibitors of Phospholipase Cγ1

Abstract

A systematic structure-activity relationship of 3β-hydroxy-27-p-E-coumaroyloxyurs-12-en-28-oic acid (7), a triterpene ester isolated from Uncaria rhynchophylla as a phospholipase Cγ1 inhibitor, was undertaken with a view toward elucidating its chemical mode of action on PLCγ1. Related derivatives and analogues of 7 were synthesized and their inhibitory activities against PLCγ1 were evaluated in vitro. The results indicate that 3-OH and 27-esterification may be essential, and that 28-COOH and the 2′ double bond appear to be important for activity. Furthermore, the compound possessing a p-coumaroyloxy at position 27 rather than at the 3 and 28 positions shows the greatest inhibitory activity against PLCγ1. Therefore, this inhibitor will be providing a chemical lead for the further development of cancer chemopreventive or cancer chemotherapeutic agents that have lower toxicity against normal tissues.

Key words

Uncaria rhynchophylla - Rubiaceae - triterpene esters - PLCγ1 - structure-activity relationship

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