title: Structure-activity relationships of the nonredox-type non-competitive leukotriene biosynthesis inhibitor acetyl-11-keto-β-boswellic acid.
abstract: Acetyl-11-keto-β-boswellic acid (AKBA) from Boswellia serrata Roxb. and italics Boswellia carterii Birdw. is the first selective, direct, non-competitive and non-redox-type inhibitor of 5-lipoxygenase, the key enzyme for leukotriene biosynthesis (Safayhi et al., 1992). Previously, we showed that AKBA interacts with the 5-lipoxygenase via a pentacyclic triterpene selective effector site (Safayhi et al., 1995). In order to study the impact of AKBA's functional groups on enzyme inhibition, natural and synthetic analogues of this boswellic acid were tested for 5-lipoxygenase inhibition in intact rat neutrophils (Sailer et al., 1996 a). The results reveal that the carboxylic group of AKBA combined with the 11-keto-group is essential for enzyme inhibition, whereas the acetoxy-group on position C-3 α increases the affinity of AKBA to its effector site. Furthermore, other experiments demonstrated that minor structural modifications could cause a total loss of binding affinity and/or inhibitory activity of these compounds.
authors.affiliation: Department of Pharmacology, Institute for Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, D-72076 Tuebingten, Germany.
authors.forename: E R
authors.initials: ER
authors.lastname: Sailer
authors.forename: R F
authors.initials: RF
authors.lastname: Hoernlein
authors.forename: H P
authors.initials: HP
authors.lastname: Ammon
authors.forename: H
authors.initials: H
authors.lastname: Safayhi