Structure-activity relationship of pentacylic triterpene esters from Uncaria rhynchophylla as inhibitors of phospholipase Cgamma1.
A systematic structure-activity relationship of 3beta-hydroxy-27- P- E-coumaroyloxyurs-12-en-28-oic acid ( 7), a triterpene ester isolated from UNCARIA RHYNCHOPHYLLA as a phospholipase Cgamma1 inhibitor, was undertaken with a view toward elucidating its chemical mode of action on PLCgamma1. Related derivatives and analogues of 7 were synthesized and their inhibitory activities against PLCgamma1 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 PLCgamma1. 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.
Lee
Ji Suk
JS
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea. jslee103@snu.ac.kr
Yoo
Hunseung
H
Suh
Young Ger
YG
Jung
Jae Kyung
JK
Kim
Jinwoong
J
D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004952:Esters; D053978:Pentacyclic Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D032070:Uncaria / Q000737:chemistry*
C533644:3beta-hydroxy-27- P- E-coumaroyloxyurs-12-en-28-oic acid; D004791:Enzyme Inhibitors; D004952:Esters; D053978:Pentacyclic Triterpenes; D051966:Phospholipase C gamma