Workup-Dependent Formation of 5-Lipoxygenase Inhibitory Boswellic Acid Analogues

Abstract

Pentacyclic triterpenes from the 11-keto-boswellic acid series were identified as the active principal ingredients of Boswellia resin, inhibiting the key enzyme of leukotriene biosynthesis, 5-lipoxygenase (5-LO). Of the genuine boswellic acids hitherto characterized, 3-O-acetyl-11-keto-beta-boswellic acid, AKBA (1), proved to be the most potent inhibitor of 5-LO. In the course of purification of further boswellic acid derivatives from Boswellia resin, we observed the degradation of the natural compound 3-O-acetyl-11-hydroxy-beta-boswellic acid (2) to the thermodynamically more stable product 3-O-acetyl-9, 11-dehydro-beta-boswellic acid (4). The metastable intermediate of this conversion, under moderate conditions of workup in methanolic solutions, was identified as 3-O-acetyl-11-methoxy-beta-boswellic acid (3). The novel artifactual boswellic acid derivatives inhibited 5-LO product formation in intact cells with different characteristics: 4 almost totally abolished 5-LO activity, with an IC(50) of 0.75 microM, whereas 3 and 9,11-dehydro-beta-boswellic acid (5), the deacetylated analogue of 4, were incomplete inhibitors. The data suggest that the conditions chosen for the workup of Boswellia extracts could significantly influence the potency of their biological actions and their potential therapeutic effectiveness.

Qualitative and Quantitative Analysis of 17 Different Types of Tetra- and Pentacyclic Triterpenic Acids in Boswellia papyrifera by a Semi-Automatic Homomodal 2D HPLC method

“…Figure 3 shows when compound 7 decreases that 10, vice versa, increases. This phenomenon was reported by Schweizer et al [28] before. Furthermore, there is also an increase of 9 referring to the assumed existence of an 11-hydroxy-b-boswellic acid, although we have not determined it yet.…”

“…As probable reason therefore, application of continuous liquid-liquid extraction (Kutscher-Steudel), where the matrix compounds were extracted for a longer time compared to the discontinuous extraction, could be determined. Hence, the metastable compound 7 reacted with the hydrochloric media leading to already known degradation products [28]. Figure 3 shows when compound 7 decreases that 10, vice versa, increases.…”

A verticillane‐type diterpene from Boswellia carterii essential oil

“…1 Especially the triterpenic acid constituents, boswellic acids, have already been shown to have pharmaceutical activity. 2,3 In previous studies of Boswellia carterii Birdw., it was reported that the diterpene fraction of olibanum contains cembrene A (cembra-3,7,11,15-tetraene) (1), 4,5 isocembrene (cembra-2,4(18),7,11-tetraene) (2), 6 incensole (4), 7 incensole oxide (5), 8 isoincensole oxide (6) 9 and incensole acetate (7) 10 (Scheme 1), but a clear indication of the provenance of the investigated samples was not given. In this study of an authentic B. carterii olibanum sample from Ethiopia, incensole and its acetate were identified by gas chromatography-mass spectrometry (GC-MS).…”

Synthesis and cytotoxic screening of beta-boswellic acid derivatives

“…Reaction of a methanolic solution of 5 or 6 with ion exchange resin IR120 H + for 1 hour at 60 °C gave pure product 9 in good yields. This compound has previously been isolated from the resin, too (but was most probably an artefact due to the acidic conditions during the isolation) 24 . The facile elimination reaction of 5 and 6 parallels previous findings of Rozen et al for glycyrrhetinic acid derivatives 25 .…”