11-Keto-α-Boswellic Acid, a Novel Triterpenoid from Boswellia spp. with Chemotaxonomic Potential and Antitumor Activity against Triple-Negative Breast Cancer Cells

Abstract

Boswellic acids, and particularly 11-keto-boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and potential antitumor efficacy. Although boswellic acids generally occur as α-isomers (oleanane type) and β-isomers (ursane type), 11-keto-boswellic acid (KBA) was found only as the β-isomer, β-KBA. Here, the existence and natural occurrence of the respective α-isomer, 11-keto-α-boswellic acid (α-KBA), is demonstrated for the first time. Initially, α-KBA was synthesized and characterized by high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy, and a highly selective, sensitive, and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed by Design of Experiments (DoE) using a pentafluorophenyl stationary phase. This method allowed the selective quantification of individual 11-keto-boswellic acids and provided evidence for α-KBA in Boswellia spp. oleogum resins. The contents of α-KBA as well as further boswellic acids and the composition of essential oils were used to chemotaxonomically classify 41 Boswellia oleogum resins from 9 different species. Moreover, α-KBA exhibited cytotoxicity against three treatment-resistant triple-negative breast cancer (TNBC) cell lines in vitro and also induced apoptosis in MDA-MB-231 xenografts in vivo. The respective β-isomer and the acetylated form demonstrate higher cytotoxic efficacies against TNBC cells. This provides further insights into the structure-activity relationship of boswellic acids and could support future developments of potential anti-inflammatory and antitumor drugs.

BAHD acetyltransferase contributes to wound‐induced biosynthesis of oleo‐gum resin triterpenes in Boswellia

“…, 2006; Schmiech et al. , 2021). We could not test whether BsAT1 catalyzes C3α‐ O ‐acetylation of 11‐keto‐αBA due to the unavailability of authentic 11‐keto‐αBA.…”

“…The semi‐synthetic 11‐keto‐αBA and 3‐acetyl‐11‐keto‐αBA have been made using the natural 3‐acetyl‐αBA; however, 11‐keto‐αBA and 3‐acetyl‐11‐keto‐αBA have not been isolated so far from the natural source, but they might be found in trace quantities in Boswellia species (Figure 1; Büchele et al. , 2006; Schmiech et al 2021). It could be possible that 11‐keto‐αBA and 3‐acetyl‐11‐keto‐αBA are biosynthesized at a low level due to the limited precursor flux towards αBAs.…”

“…Notably, 11‐keto‐αBA and 3‐acetyl‐11‐keto‐αBA have been semi‐synthesized from 3‐acetyl‐αBA (Büchele et al. , 2006; Schmiech et al 2021). Oxidosqualene cyclase and cytochrome P450 monooxygenase potentially catalyze triterpene cyclization and oxidation reactions (C11 and C24) in the BA biosynthetic pathway.…”

Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects

“…Desmethoxyyangonin, dihydromethysticin, flavokawain A, and flavokawain C, as the major chemical constituents of Piper methysticum Forst., have exhibited significant anti-inflammatory, anti-cancer, and neuro-protective effects [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. 11-keto-β-boswellic acid is a triterpenoid found in Boswellia serrata and has potential therapeutic efficacy against several chronic inflammatory diseases and neurodegenerative diseases [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Asperuloside, which is classified under the category of iridoid glycosides, has potential for the treatment of obesity, inflammatory diseases, cancer, bacterial infection, and renal fibrosis [ 61 , 62 , 63 , 64 , 65 , 66 ].…”

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“…The 11-keto-α-Boswellic acid was evaluated for the anti-tumour activity in the breast cancer cell line. It resulted in cytotoxicity against triple-negative breast cancer cells and also induced apoptosis in the cell line 42 . The Boswellic acids have been proven to have cytotoxic activity.…”