11-Keto-Alpha-Boswellic Acid, A Novel Triterpenoid From Boswellia Spp. With Chemotaxonomic Potential And Antitumor Activity Against Triple-Negative Breast Cancer Cells

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 alpha-isomers (oleanane type) and beta-isomers (ursane type), 11-keto-boswellic acid (KBA) was found only as the beta-isomer, beta-KBA. Here, the existence and natural occurrence of the respective alpha-isomer, 11-keto-alpha-boswellic acid (alpha-KBA), is demonstrated for the first time. Initially, alpha-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 alpha-KBA in Boswellia spp. oleogum resins. The contents of alpha-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, alpha-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 beta-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.