title: Structure-activity relationship of pentacylic triterpene esters from Uncaria rhynchophylla as inhibitors of phospholipase Cgamma1.
abstract: 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.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea. jslee103@snu.ac.kr
authors.forename: Ji Suk
authors.initials: JS
authors.lastname: Lee
authors.forename: Hunseung
authors.initials: H
authors.lastname: Yoo
authors.forename: Young Ger
authors.initials: YG
authors.lastname: Suh
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Kim
mesh_terms: 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*
chemical_list: C533644:3beta-hydroxy-27- P- E-coumaroyloxyurs-12-en-28-oic acid; D004791:Enzyme Inhibitors; D004952:Esters; D053978:Pentacyclic Triterpenes; D051966:Phospholipase C gamma