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DOI: 10.1055/s-2008-1081348
© Georg Thieme Verlag KG Stuttgart · New York
Structure-Activity Relationship of Pentacylic Triterpene Esters from Uncaria rhynchophylla as Inhibitors of Phospholipase Cγ1
Publication History
Received: April 13, 2008
Revised: June 22, 2008
Accepted: June 24, 2008
Publication Date:
24 September 2008 (online)
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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Prof. Ji Suk Lee
College of Pharmacy andResearch Institute ofPharmaceutical Sciences
Department of Pharmacognosy
Seoul National University
599 Kwanangno
Kwanak-gu
Seoul 151–742
Korea
Phone: +82-2-880-7853
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Email: jslee103@snu.ac.kr