Ponapensin, a Cyclopenta[bc]benzopyran with Potent NF‐ϰB Inhibitory Activity from Aglaia ponapensis.

Salim, Angela A.; Pawlus, Alison D.; Chai, Heebyung; Farnsworth, Norman R.; Kinghorn, A. Douglas; Carcache‐Blanco, Esperanza J.

doi:10.1002/chin.200720200

Cited by 13 publications

(36 citation statements)

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“…Previously, only a limited number of cyclopenta [b]benzopyran-type has been tested for the NF-κB inhibitory activity, 23,24 and only one showed potent NF-κB inhibitory activity. 23 The isolation of silvestrol (1) in this investigation is significant, since the leaves of A. foveolata potentially could be used as a renewable resource for the future supply of this promising antileukemic agent, in the event of its further development.…”

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confidence: 99%

Constituents of the leaves and stem bark of Aglaia foveolata

et al. 2007

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The previously known potent cytotoxic agent silvestrol (1) (0.002% w/w yield) and five new flavagline derivatives (2-6) were isolated from the leaves of Aglaia foveolata collected in Indonesia. The new compound 5 has an unprecedented cyclic amide moiety in its cyclopenta [b]benzopyran skeleton, while compound 6 is a novel benzo [b]oxepine derivative in which the oxepine ring is cleaved. Pyramidatine (7), a biogenetic precursor of the new flavaglines 2-6, was isolated from the leaf extract investigated. Silvestrol was also isolated from the stem bark of A. foveolata (yield of 0.02% w/w) along with a new baccharane-type triterpenoid (8). The structures of the new compounds were elucidated on the basis of their NMR and mass spectrometric data. All new compounds isolated were tested against a panel of cancer cell lines, but only compound 2 was cytotoxic (IC 50 range = 1.4-1.8 μM), and is the first member of the cyclopenta[b]benzopyran class found to exhibit this type of activity. Compound 2 also showed significant NF-κB inhibitory activity in an Elisa assay (IC 50 = 0.37 μM).

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confidence: 99%

Constituents of the leaves and stem bark of Aglaia foveolata

et al. 2007

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“…These proton signals suggested that 1 is based on a typical cyclopenta [b]benzopyran skeleton as found previously in several other Aglaia species. 3,10,12,41,42 Besides the signals ascribed to the general cyclopenta [b]benzopyran skeletal feature, a putrescinyl 4-hydroxytiglate moiety was recognized. The latter was based on the carbon signals of four CH 2 groups at δ C 38.3 (C-13), 27.9 (C-14), 26.2 (C-15) and 39.8 (C-16), a carbonyl group at δ C 169.6 (C-18), a trisubstituted double bond at δ C 133.…”

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confidence: 99%

“…which revealed the presence of four rocaglaol derivatives (9)(10)(11)(12). In addition, the occurrence of unknown cytotoxic compounds was suggested with possible molecular formulas of C 29 H 28 O 9 and C 27 H 26 O 7 .…”

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“…Cyclopenta [b]benzopyran derivatives, with most of them being rocaglaol and related analogues, and triterpenoids, mainly of the glabretal-, baccharane-, and dammarane-types, were isolated as the major constituents from the above-mentioned taxa. [6][7][8][9][10][11][12][13] Among the flavaglines from Aglaia species, two cyclopenta [b]benzofurans have been reported to exhibit inhibitory activity in vivo in tumor-bearing experimental animals, 2-5 namely, rocaglamide 14 and silvestrol. 9,[15][16][17][18] Silvestrol was isolated and fully structurally characterized from A. foveolata Pannell 9 , obtained from Kalimantan, Indonesia, and also obtained from A.…”

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Bioactive Flavaglines and Other Constituents Isolated from Aglaia perviridis

Li¹,

Acuña²,

Li³

et al. 2013

Planta Med

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Eight new compounds, including two cyclopenta [b]benzopyran derivatives (1, 2), two cyclopenta [b]benzofuran derivatives (3, 4), three cycloartane triterpenoids (5-7), and an apocarotenoid (8), together with 16 known compounds, were isolated from the chloroform-soluble partitions of separate methanol extracts of a combination of the fruits leaves and twigs, and of the roots of Aglaia perviridis collected in Vietnam. Isolation work was monitored using human colon cancer cells and facilitated with an LC/MS dereplication procedure. The structures of the new compounds (1-8) were determined on the basis of spectroscopic data interpretation. The Mosher ester method was employed to determine the absolute configurations of 5-7, and the absolute configurations of the 9,10-diol unit of compound 8 was established by a dimolybdenum tetraacetate [Mo 2 (AcO) 4 ] induced circular dichroism (ICD) procedure. Seven known rocaglate derivatives (9-15) exhibited significant cytotoxicity against the HT-29 cell line, with rocaglaol (9) being the most potent (ED 50 0.0007 µM). The new compounds 2-4 were also active against this cell line, with ED 50 values ranging from 0.46 to 4.7 µM. The cytotoxic compounds were evaluated against a normal colon cell line, CCD-112CoN. In addition, the new compound perviridicin B (2), three known rocaglate derivatives (9, 11, 12), as well as a known sesquiterpene, 2-oxaisodauc-5-en-12-al (17), showed significant NF-κB (p65) inhibitory activity in an ELISA assay.* Corresponding Author. Tel: +1-614-247-8094. Fax: +1-614-247-8119. kinghorn@pharmacy.ohio-state.edu. # Dedicated to Dr. Lester A. Mitscher, of the University of Kansas, for his pioneering work on the discovery of bioactive natural products and their derivatives ASSOCIATED CONTENT Supporting Information. 1 H, 13 C and 2D NMR spectra of compounds 1-8, 1 H NMR of (R)-and (S)-MTPA esters of 5-7. This material is available free-of-charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript J Nat Prod. Author manuscript; available in PMC 2014 March 22. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAglaia Lour., containing more than 120 species, is the largest genus of the plant family Meliaceae. 1 Aglaia species have attracted considerable interest in the area of natural products research, since they are a rich source of the "flavagline" class of bioactive agents. Flavagline derivatives have been proposed to be biogenetically derived from the coupling of a flavonoid unit and a cinnamic acid amide moiety, and can be divided into three subtypes, namely, the cyclopenta [b]benzofurans, the cyclopenta [b]benzopyrans, and the benzo [b]oxepines. [2][3][4][5] More than 100 flavaglines have been isolated from over 30 Aglaia species to date. [2][3][4][5] In a search for new anticancer agents from tropical plants, several Aglaia species, including Aglaia crassinervia, 6 A. edulis, 7 A. elliptica, 8 A. foveolata, 9-11 A. ponapensis, 12 and A. rubiginosa, 13 mainly collected from Indonesia, have been in...

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“…The plant genus Aglaia produces a number of secondary metabolites including the cyclopenta [b]benzofurans [1] rocaglamide 1, silvestrol 2, and cyclopenta [b,c]benzopyrans [2] (aglains) including ponapensin 3 (Figure 1). Cyclopenta [b]benzofuran natural products possess potent anticancer properties due to modulation of the activity of the RNA helicase eukaryotic initiation factor 4A (eIF4A), which is involved in loading ribosomes onto mRNA templates during translation initiation, a step frequently deregulated in cancer.…”

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