Article Cite This: J. Nat. Prod. 2018, 81, 307−315
pubs.acs.org/jnp
Structurally Diverse Cytotoxic Dimeric Chalcones from Oxytropis chiliophylla Yang Liu,† Xiaojing Zhang,† Norbo Kelsang,† Guangzhong Tu,‡ Dexin Kong,§ Jianghai Lu,*,⊥ Yingtao Zhang,† Hong Liang,† Pengfei Tu,† and Qingying Zhang*,† †
State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, People’s Republic of China ‡ Beijing Institute of Microchemistry, Beijing 100091, People’s Republic of China § School of Pharmaceutical Sciences, Tianjin Medical University, Tianjin 300070, People’s Republic of China ⊥ National Anti-Doping Laboratory, China Anti-Doping Agency, Beijing 100029, People’s Republic of China S Supporting Information *
ABSTRACT: Ten isomeric cyclobutane- and cyclohexenecontaining chalcone dimers, oxyfadichalcones A−G, were isolated from the aerial parts of Oxytropis chiliophylla. These included six new compounds and three pairs of enantiomers that are being reported from natural sources for the first time. The relative configurations were elucidated by spectroscopic data analysis, while the absolute configurations were determined by comparing the experimental and calculated electronic circular dichroism spectra. Quantitative LC-MS analysis of the main dimers from different parts of the plant revealed their characteristic accumulation in the viscous secretion and provided supporting evidence for the hypothesized photochemical biosynthesis. In addition, the cytotoxic activities of all isolates against the PC-3 human prostate cancer cell line are reported. triterpenoid, and four other compounds from the herb.12,13 In this study, we focused primarily on the isolation and identification of the characteristic chalcone dimers guided by LC-QTOF/MS. As a result, 10 isomeric cyclobutane- and cyclohexene-containing chalcone dimers, oxyfadichalcones A− G (1−3, 4a, 4b, 5, 6a, 6b, 7a, and 7b) (Figure 2), were obtained from the aerial parts of O. chiliophylla. Among the isolated compounds were six new compounds (2, 4a, 4b, 5, 6a, and 6b) and three new pairs of enantiomers (4a/4b, 6a/6b, and 7a/7b) that have not previously been reported from natural sources. Subsequently, the characteristic distribution of the main chalcone dimers in different parts of O. chiliophylla, including the viscous secretion, aerial parts after removal of the viscous secretion, and underground parts, was determined using an LC-MS method in multireaction monitoring (MRM) mode. The cytotoxic activities of all isolates were evaluated against the PC-3 human prostate cancer cell line.
Oxytropis chiliophylla Royle (Leguminosae) and Oxytropis falcate Bunge are the official botanical origin of the Tibetan medicine “Er-Da-Xia”, which, in the Chinese Pharmacopoeia, is regarded as the “King of Herbs” and has been widely used for the treatment of inflammation, fever, and bleeding for thousands of years.1,2 Many phytochemical and pharmaceutical investigations of O. falcata have been carried out and revealed that flavonoids, oleanane-type triterpenoids, and N-benzoylindole alkaloids are the principle constituents.3−7 Of these, flavonoids are known to have significant anti-inflammatory and analgesic activities.8,9 Three novel cyclobutane-containing chalcone dimers, oxyfadichalcones A−C, the biosyntheses of which might be related to the intense ultraviolet irradiation on the Qinghai-Tibet Plateau, have been isolated from O. falcate. However, some questions, including their absolute configurations, full structural assignments, and biological and ecological properties, remain unanswered due to limitations in quantity.7 O. chiliophylla, the main components of which are similar to those of O. falcata,10 is mainly found at altitudes of 2800−5200 m in the Tibet and Xinjiang Uygur Autonomous Regions in China, but this species is well known for the characteristic viscous secretion on the surface of its aerial parts.11 Moreover, investigations of O. chiliophylla are rare, and just two papers have reported the isolation of a total of 17 flavonoids, a © 2018 American Chemical Society and American Society of Pharmacognosy
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RESULTS AND DISCUSSION O. chiliophylla was first screened for the potential chalcone dimers formed from two different chalcone monomers using LC-QTOF/MS in negative ionization mode by extracting the Received: August 27, 2017 Published: February 5, 2018 307
DOI: 10.1021/acs.jnatprod.7b00736 J. Nat. Prod. 2018, 81, 307−315
Journal of Natural Products
Article
Figure 1. Extracting ion chromatogram of the aerial parts of O. chiliophylla generated by extracting m/z 479.1500 [M − H]− with the mass accuracy of
