Preparation of Novel Analogues of the Nonredox‐Type Non‐Competitive Leukotriene Biosynthesis Inhibitor AKBA

Abstract

AbstractAKBA (acetyl‐11‐keto‐β‐boswellic acid, 1) and KBA (11‐keto‐β‐BA, 2) from Boswellia serrata Roxb. and Boswellia carterii Birdw. are direct, nonredox‐type inhibitors of 5‐lipoxygenase, the key enzyme for leukotriene biosynthesis (IC50 = 1.5 and 3μM in intact neutrophils, respectively). In order to study the impact of the carboxyl function for enzyme inhibition, we synthesized novel analogues of boswellic acids. The C‐4 alcohol derivative of KBA (4) still exerted 5‐lipoxygenase inhibitory activity (IC50 = 4.5 μM), whereas (8), the C‐4 alcohol analogue of β‐boswellic acid (7), the methyl ester analogue of KBA (5), and acetyl‐11‐keto‐amyrin (9) possessed no inhibitory potential in concentrations up to 50 μM. These findings reveal that a hydrophilic group at C4 in combination with an 11‐keto‐function is essential for 5‐lipoxygenase inhibition by boswellic acids.