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Preparation of Novel Analogues of the Nonredox‐Type Non‐Competitive Leukotriene Biosynthesis Inhibitor AKBA
Author(s) -
Sailer EckartRoderich,
Hoernlein Rainer F.,
Subramanian Lakshminarayanapuram R.,
Ammon Hermann P. T.
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290110
Subject(s) - boswellia serrata , chemistry , biosynthesis , enzyme , arachidonate 5 lipoxygenase , lipoxygenase , stereochemistry , biochemistry , enzyme inhibitor , ic50 , alcohol , in vitro , arachidonic acid , medicine , alternative medicine , pathology
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 (IC 50 = 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 (IC 50 = 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.