Bioactive drimane sesquiterpenoids and aromatic glycosides from Cinnamosma fragrans

https://doi.org/10.1016/j.bmcl.2017.02.067Get rights and content

Abstract

Phytochemical investigation of the ethyl acetate and methanol extracts of the bark of Madagascan endemic and medicinal plant Cinnamosma fragrans led to the isolation of two drimane sesquiterpene derivatives: cinnafragroside A (1) and cinnafragrin E (2), two aromatic glycosides: 3,4,5-trimethoxyphenol 1-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (3) and 3,4-dimethoxyphenyl-1-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (4), together with 12 known compounds identified as: helicide (6), 1-(α-l-rhamnosyl(1→6)-β-d-glucopyranosyloxy)-3,4,5-trimethoxybenzene (7), vanilloloside (8), cinnamadin (9), ugandensolide (10), cinnamosmolide (11), cinnamolide (12), polygodial (13), cinnamodial (14), bemadienolide (15), 4-isopropyl-6-methyl-α-tetralone (16), and capsicodendrin (17). Another new compound, 11-norcinnafragrolide-9-one (5), was obtained during chemical derivatization of capsicodendrin and gave a hint to understanding the structure required for the antiproliferative activity of 17. The structures of the new compounds were elucidated based on the interpretation of their spectroscopic data including one and two dimensional nuclear magnetic resonance (1D- and 2D-NMR) and mass spectroscopic data. All isolated compounds were evaluated against the hormone dependent breast cancer cell line MCF-7. Compound 17 exhibited the most potent activity with an IC50 value of 0.6 μM. Our preliminary SAR study showed that the hydroxyl group at C-12′ and the presence of conjugated carbonyl contribute to the antiproliferative activity.

Section snippets

Note

The authors declare no competing financial interest.

Acknowledgements

This work was supported by the Public Health Prepardness for Infectious Diseases (PHPID) New Investigator Grant (To L.H.R) of The Ohio State University, U.S., Public Health Preparedness for Infectious Diseases (PHPID) New Investigator Grant (to L.H.R). We thank the instrumentation facility of the College of Pharmacy and the Campus Chemical Instrument Center (CCIC) of The Ohio State University for the acquisition of the NMR, Mass, UV, and IR spectroscopic data.

References (18)

  • C.J.W. Brooks et al.

    Tetrahedron

    (1969)
  • S.A. Opiyo et al.

    Phytochemistry Lett.

    (2011)
  • L. Canonica et al.

    Tetrahedron Lett

    (1967)
  • L. Canonica et al.

    Tetrahedron

    (1969)
  • T.-L. Ho et al.

    Tetrahedron

    (1995)
  • J.O. Andrianaivoravelona et al.

    Phytochemistry

    (1999)
  • Y. Ida et al.

    Phytochemistry

    (1993)
  • C.Y. Tan et al.

    Phytochem Lett

    (2017)
  • M. Randrianarivelojosia et al.

    Malar J

    (2003)
There are more references available in the full text version of this article.

Cited by (22)

  • Scalable total synthesis of natural vanillin-derived glucoside ω-esters

    2022, Carbohydrate Research
    Citation Excerpt :

    Other examples of pharmaceutically-active aryl glycosides include gastrodin [9], trichocarpine [10–12], curculigosides [13,14], and ovatosides [15] (Fig. 1). The vanillyl alcohol glycoside vanilloloside (1) is another structural analog of salicin that has been isolated from Nitraria sibirica [1], Zaleya pentandra [2], Bletilla striata, [3] Alangium alpinum, [16] Cinnamosma fragrans [17], and other medicinal herbs. A demethylated analogue of vanilloloside — calleryanin (2) — has been isolated from Strychnos axillaris [18] and several plants of genera Pyrus and Prunus [4,5].

  • Structural characterization of phenolic constituents from the rhizome of Imperata cylindrica var. major and their anti-inflammatory activity

    2022, Phytochemistry
    Citation Excerpt :

    On the basis of above-mentioned evidence, the absolute configuration of imperlignanoside D (10) was clarified to be 7S,7′S,8S,8′R. By comparing the spectroscopic data with those reported in literatures, the structures of known compounds 11–47 were identified as 4-hydroxy-3-methoxy phenyl-β-d-xylopyranosyl (1 → 6)-O-β-d-glucopyranoside (11) (Lin et al., 2010), cuneataside D (12) (Jin et al., 2015), 3,4-dimethoxyphenyl-β-d-glucopyranoside (13) (Xuan et al., 2006), 3,4-dimethoxyphenyl-1-O-β-d-apiofuranosyl (1 → 6)-β-d-glucopyranoside (14) (He et al., 2017), 3,4-dimethoxyphenyl-6-O-(α-l-rhamnopyranosyl)-β-d-glucopyranoside (15) (Jin et al., 2015), 3,4,5-trimethoxyphenyl 1-O-β-apiofuranosyl (1''→6′)-β-glucopyranoside (16) (Kanchanapoom et al., 2002), salicin (17) (Mizuno et al., 1991), 2′-O-(E)-p-coumaroylsalicin (18) (Dagvadorj et al., 2010), poliothrysoside (19) (Shaari and Waterman, 1994), salireposide (20) (Belyanin et al., 2012), 4′-hydroxybenzyl-2-hydroxybenzoate-1′-O-β-d-glucopyranoside (21) (Hou et al., 2021), p-hydroxybenzaldehyde (22) (Kim et al., 2003), p-hydroxybenzoic acid (23) (Demmak et al., 2019), 3,4-dihydroxybenzoic acid (24) (Song et al., 2007), 3-methoxy-4-hydroxybenzoic acid (25) (Kong et al., 1996), 4-hydroxy-3,5-dimethoxybenzaldehyde (26) (Wang et al., 2017), syringic acid (27) (Hu et al., 2006), glucosyringic acid (28) (Ma et al., 2020), echipuroside A (29) (Li et al., 2002), 4-hydroxy cinnamic acid (30) (Yang et al., 2014), caffeic acid (31) (Zhang et al., 2006), ethyl caffeate (32) (Shen et al., 2010), coniferaldehyde (33) (Song et al., 2008), ferulic acid (34) (Yang et al., 2001), (+)-(7S,8S)-guaiacylglycerol (35) (Gan et al., 2010; Tian et al., 2014; Wang et al., 2014; Warashina et al., 2005), (+)-(7S,8S)-guaiacylglycerol 8-O-β-d-glucopyranoside (36) (Gan et al., 2010; Qu et al., 2014), (7S,8S)-syringoylglycerol (37) (Gan et al., 2010; Matsuura et al., 2004; Wang et al., 2014), (7R,8R)-4-O-methylsyringoylglycerol (38) (Gan et al., 2010; Liu et al., 2012; Matsuura et al., 2004; Wang et al., 2014), 1,2′,4′,6′-tetraacetyl-3,6-diferuloyl-sucrose (39) (Li et al., 2013), sucrose diester of 4,4′-dihydroxy-3,3′-dimethoxy-β-truxinic acid (40) (Dinberg et al., 2001; Xu et al., 2016; Zhang et al., 2016), (−)-syringaresinol-4-O-β-d-glucopyranoside (41) (Shao et al., 2018; Yan et al., 2009), (6R,7S,8S)-7α-[(β-glucopyranosyl)oxy]lyoniresinol (42) (Ohashi et al., 1994; Ono et al., 2009), 5-methoxyflavone (43) (Fu et al., 2010), 6-hydroxy 5-methoxyflavone (44) (Awaad et al., 2006), 5,2′-dimethoxyflavone (45) (Lee et al., 2008), tricin 4′-O-(erythro-β-guaiacylglyceryl) ether (46) (Nakajima et al., 2003), tricin 4′-O-(erythro-β-4-hydroxyphenylglyceryl) ether (47) (Chang et al., 2010), respectively. The effects of compounds 1–47 on lipopolysaccharides (LPS)-stimulated nitric oxide (NO) release in RAW264.7 cells were measured through the Griess reaction at the concentration without significant cytotoxicity (Fig. S70) to clarify their potentical anti-inflammatory effects (Chen et al., 2020).

  • Analysis of herbal bioactives

    2021, Aromatic Herbs in Food: Bioactive Compounds, Processing, and Applications
  • Stop the crop: Insights into the insecticidal mode of action of cinnamodial against mosquitoes

    2021, Pesticide Biochemistry and Physiology
    Citation Excerpt :

    In some experiments we used a ‘zero Ca2+’ Ringer's solution in which CaCl2 was excluded and 1 mM EGTA (Thermo Fisher Scientific, Waltham, MA) was added. All natural drimane sesquiterpenes were isolated from medicinal plants and their structures were determined as previously described (He et al., 2017; Inocente et al., 2019; Inocente et al., 2018; Manwill et al., 2020). In brief, cinnamodial (CDIAL), polygodial (POLYG), ugandensolide (UGAN), cinnamosmolide (CMOS), cinnamolide (CML), drimenin (DRIM), and capsicodendrin (CPCD) were isolated from the bark of Cinnamosma fragrans Baill (Canellaceae), whereas warburganal (WARB) was isolated from the bark of Warburgia ugandensis Sprague (Canellaceae) (Inocente et al., 2019).

  • Bioactive drimane sesquiterpenoids and isocoumarins from the marine-derived fungus Penicillium minioluteum ZZ1657

    2020, Tetrahedron Letters
    Citation Excerpt :

    Its 1H NMR spectrum displayed characteristic signals for one oxymethylene (δH 4.52 and 4.20) and three methyls (δH 0.93, 0.92, 0.73). The NMR and HRESIMS data mentioned above suggested that 3 is an analogue of 1α-hydroxyconfertifolin (8) and cinnamolide [29] with two hydroxy moieties. The HMBC correlations (Fig. 5) of H-1 (δH 3.84, br t, 2.5 Hz) with C-3 (δC 33.8) and C-5 (δC 36.5), H-7 (δH 6.86, t, 4.1 Hz) with C-5, C-6 (δC 25.0), C-9 (δC 78.3), and C-12 (δC 168.6), H-15 (δH 0.73, 3H, s) with C-1, C-9, and C-10 (δC 39.5), and all of H-5 (δH 2.38, dd, 11.1, 5.6 Hz), H-11a (δH 4.52, d, 10.1 Hz), and H-11b (δH 4.20, d, 10.1 Hz) with C-9 demonstrated the presences of a C7-8 double bond and the two hydroxy moieties at C-1 and C-9 in 3.

View all citing articles on Scopus
View full text