Discovery of diverse diterpenoid scaffolds from Euphorbia antiquorum and their activity against RANKL-induced osteoclastogenesis

Yin, Zhiyong; Yan, Detian; Peng, Hua; Sun, Zhejun; Cheng, Yanfang; Yuan, Shengheng; Chen, Ziyang; Gu, Qiong

doi:10.1016/j.bioorg.2019.103292

Cited by 17 publications

(19 citation statements)

References 24 publications

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“…Diterpenoid esters 1-9 were described earlier from only a few plant species. Ingol 3,12diacetate 7-tigliate (1) was previously isolated from E. hermentiana [28], 8-O-methyl-ingol 3,12-diacetate 7-tigliate (2) from E. acrurensis [29], E. hermentiana [28], and E. kamerunica [30], 8-O-methyl-ingol 3,12-diacetate 7-benzoate (3) from E. antiquorum [31], E. hermentiana [28], and E. kamerunica [30], ingol 3,7,12-triacetate 8-benzoate (4) from E. antiquorum [31], E. nivulia [16,32] E. hermentiana [28], and E. kamerunica [33], and ingol 3,7,12-triacetate 8-tigliate (5) from E. antiquorum [31], and E. kamerunica [33]. The ingenane-type compound 17acetoxyingenol 3-angelate 20-acetate (6) was previously reported from E. canariensis [34] and E. hermentiana [35], 17-acetoxyingenol 3 angelate 5,20-diacetate ( 7) from E. hermentiana [35], E. kamerunica [30], E. royleana [36], and E. trigona [20], 17-acetoxy-20-deoxyingenol 3-angelate ( 8) from E. acrurensis [29], E. hermentiana [35] and E. trigona [20], and 17-acetoxy-20-deoxyingenol 5-angelate ( 9) from E. hermentiana [35].…”

Section: Resultsmentioning

confidence: 99%

Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity

Hammadi

Kúsz

Dávid

et al. 2021

Plants

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Ingenol mebutate, isolated from Euphorbia peplus, is an ingenane-type diterpenoid, primarily used for the topical treatment of actinic keratosis, a premalignant skin condition. The aim of our work was to investigate other Euphorbia species to find structurally similar diterpenes that can be used as alternatives to ingenol mebutate. Pharmacological investigation of Euphorbia candelabrum, Euphorbia cotinifolia, Euphorbia ramipressa, and Euphorbia trigona revealed the potent keratinocyte (HPV-Ker cell line) inhibitory activity of these spurge species. From the methanolic extract of the aerial parts of Euphorbia trigona Miller, the most active species, five ingol (1–5) and four ingenane-type diterpenoids (6–9) were isolated by various chromatographic separation techniques, including open column chromatography, vacuum liquid chromatography, thin-layer chromatography, and high-performance liquid chromatography. The structures of the compounds were determined by NMR spectroscopic analysis and by comparison of the assignations with the literature data. The cytotoxic activity of the compounds against keratinocytes was tested in vitro by using ingenol mebutate as a positive control. Among the isolated compounds, two ingenane derivatives (6 and 7) exhibited remarkably stronger cytotoxic activity (IC50 values 0.39 μM and 0.32 μM, respectively) on keratinocytes than ingenol mebutate (IC50 value 0.84 μM). These compounds could serve as starting materials for further investigations to find alternatives to Picato® (with active substance ingenol mebutate), which was withdrawn from marketing authorization in the European Union.

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Section: Resultsmentioning

confidence: 99%

Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity

Hammadi

Kúsz

Dávid

et al. 2021

Plants

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“…Euphorbia antiquorum L., a medicinal plant, has traditionally been used for various treatments, for example, the latex has been used for emetic, purgative, and diuretic treatments, and the fresh stems for treatment of skin sores, scabies, and toothache [1][2][3]. Previous chemical studies on E. antiquorum in Thailand, Vietnam, and China have reported the wealth of diterpenoids, including lathyane, ent-atisane, ent-abietane, and ent-kaurane types [3][4][5][6][7][8]. Those isolated compounds showed various biological activities including cytotoxic, antiinflammatory, anti-HIV activities, and the inhibition of nitric oxide (NO) production [9].…”

Section: Introductionmentioning

confidence: 99%

“…As a continuation of our discovery of alpha-glucosidase inhibitory metabolites from E. antiquorum [10], the further investigation on the Vietnamese plant E. antiquorum L. was performed. In this paper, the isolation and structural elucidation of seven diterpenoids, ent-1α,3α,16β,17tetrahydroxyatisane (1), ethyl ent-3,4-seco-4,16β,17-trihydroxyatisane-3-carboxylate (2), entatisane-3-oxo-16β,17-acetonide (3) [11], ent-3α-acetoxy-16β,17-dihydroxyatisane (4) [12], ent-16β,17-dihydroxyatisane-3-one (5) [13], calliterpenone (6) [14], and ingol 12-acetate (7) [15] (Figure 1) from the most bioactive fraction of the title plant are reported. Their structures were elucidated by spectroscopic data analysis and compared with literature data.…”

Section: Introductionmentioning

confidence: 99%

Alpha-Glucosidase Inhibitory Diterpenes from Euphorbia antiquorum Growing in Vietnam

Tran

Dao²,

Tran³

et al. 2021

Molecules

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Bioactive-guided phytochemical investigation of Euphorbia antiquorum L. growing in Vietnam led to the isolation of five ent-atisanes, one seco-ent-atisane, and one lathyrane (ingol-type). The structures were elucidated as ent-1α,3α,16β,17-tetrahydroxyatisane (1), ethyl ent-3,4-seco-4,16β,17-trihydroxyatisane-3-carboxylate (2), ent-atisane-3-oxo-16β,17-acetonide (3), ent-3α-acetoxy-16β,17-dihydroxyatisane (4), ent-16β,17-dihydroxyatisane-3-one (5), calliterpenone (6), and ingol 12-acetate (7). Their chemical structures were unambiguously determined by analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry, as well as by comparison with literature data. Among them, 1 is a new compound while 2 is an ethylated artifact of ent-3,4-seco-4,16β,17-trihydroxyatisane-3-carboxylic acid, a new compound. Isolates were evaluated for alpha-glucosidase inhibition. Compound 3 showed the most significant inhibitory activity against alpha-glucosidase with an IC50 value of 69.62 µM. Further study on mechanism underlying yeast alpha-glucosidase inhibition indicated that 3 could retard the enzyme function by noncompetitive.

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“…As an ongoing searching for anti-osteoporosis active natural products, [36,37] chemical constituents of A. nipponensis and their activities were evaluated for their ability against RANKL-induced osteoclastogenesis. Fifteen compounds, including two new diterpenoids (1 and 14) and thirteen known ones (2 -13 and 15), were isolated from the whole plants of A. nipponensis ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Diterpenoids from the Whole Plants of Ajuga nipponensis and Their Inhibition of RANKL‐Induced Osteoclastogenesis

Wang

Teng

Zhang

et al. 2020

Chemistry & Biodiversity

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Two new diterpenoids, ajudecunoid A (1) and ajudecunoid B (14), along with thirteen known diterpenoids, were isolated from the whole plants of Ajuga nipponensis Makino. Their structures were elucidated by the extensive spectroscopic analysis (UV, IR, MS, and NMR). The absolute configurations of ajudecunoid A (1) and ajudecunoid B (14) were defined through analysis of X-ray crystallography. Fifteen compounds were evaluated for inhibition of the formation of osteoclasts in bone marrow-derived macrophages (BMM) cells. Two neoclerodane diterpenoids ajuganipponin B (5) and (12S)-6α,19-diacetoxy-18-chloro-4α-hydroxy-12-tigloyloxy-neoclerod-13-en-15,16-olide (12) showed significant inhibition of osteoclastogenesis with IC 50 values of 0.88 and 0.79 μM, respectively. Here we firstly reported diterpenoids with anti-osteoclastogenesis activity from A. nipponensis.

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Discovery of diverse diterpenoid scaffolds from Euphorbia antiquorum and their activity against RANKL-induced osteoclastogenesis

Cited by 17 publications

References 24 publications

Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity

Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity

Alpha-Glucosidase Inhibitory Diterpenes from Euphorbia antiquorum Growing in Vietnam

Diterpenoids from the Whole Plants of Ajuga nipponensis and Their Inhibition of RANKL‐Induced Osteoclastogenesis

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