| Abstract: | AKBA (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. |
