Chemistry and Biological Activity of Rocaglamide Derivatives and Related Compounds in Aglaia Species (Meliaceae)

Proksch, Peter; Edrada, Ru Angelie; Ebel, Rainer; Bohnenstengel, Frank; Nugroho, Bambang W.

doi:10.2174/1385272013375049

Cited by 130 publications

(127 citation statements)

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“…The structural variation and biological properties of the flavaglines have been reviewed recently. 5,6 There have been only two previous studies on Aglaia foveolata Pannell, which was studied initially by a collaborative French and Malaysian research group, and afforded two new dammarane-type triterpenes, foveolins A and B. 7 In a later study, silvestrol and its isomer, episilvestrol, were identified as constituents of A. foveolata during a screening program for new antitumor agents from plants, 8 as part of a multidisciplinary, collaborative natural products drug discovery project.…”

Section: Introductionmentioning

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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Section: Introductionmentioning

confidence: 99%

Constituents of the leaves and stem bark of Aglaia foveolata

et al. 2007

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“…21 Activation of the stress-response c-Jun N-terminal protein kinase (JNK) may also promote c-FLIP L ubiquitination through phosphorylation of the E3 ubiquitin ligase Itch. 22,23 We have previously shown that Rocaglamide (Roc), a naturally occurring herbal compound, derived from the traditional Chinese medicinal plant Aglaia (for reviews, see Proksch et al 24 and Kim et al 25 ), preferentially induces apoptosis in malignant but not normal proliferating lymphocytes. 26 This preference has been partially explained by its activation of the stress-response mitogen-activated protein kinases (MAPK) p38 and JNK in contrast to suppression of survival MAPK ERK activity in malignant, but not normal cells.…”

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Rocaglamide breaks TRAIL resistance in HTLV-1-associated adult T-cell leukemia/lymphoma by translational suppression of c-FLIP expression

et al. 2010

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The human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL) is incurable by currently known therapies. ATL samples and cell lines derived from ATL patients show restricted sensitivity to tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL) and CD95 ligand (CD95L). We have recently shown that HTLV-1-infected cells express elevated levels of cellular caspase-8 FLICE-inhibitory protein (c-FLIP) conferring resistance to receptor-mediated apoptosis. This finding underscores the demand to develop new strategies for treatment of ATL. In this study, we show that the naturally occurring herbal compound Rocaglamide (Roc) sensitizes CD95L-and TRAIL-induced apoptosis in HTLV-1-infected cells by downregulation of c-FLIP expression. Investigation of the molecular mechanism of Roc-mediated downregulation of c-FLIP revealed that it inhibits phosphorylation of the translation initiation factor 4E (eIF4E), a key factor that controls the rate-limiting step of translation, through inhibition of the MEK-ERK-MNK1 signaling pathway. This event prevents de novo synthesis of short-lived proteins such as c-FLIP in HTLV-1-infected cells. Our data suggest that Roc may serve as an adjuvant for TRAIL-based anticancer therapy.

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“…To date, about 60 naturally occurring cyclopenta[b]benzofuran type compounds, many of which exhibit insecticidal and antiproliferative activities, have been isolated from over 30 Aglaia species. 3,4 The cyclopenta[b]benzofurans and two structurally related groups, the cyclopenta[bc]-benzopyrans and benzo [b]oxepines, are considered characteristic secondary metabolites of the genus Aglaia, because they have been isolated only from this taxon. 3 The collective name "flavagline" has been proposed for these compounds because their mutual biogenetic origin has been postulated to be a flavonoid nucleus linked to a cinnamic acid moiety.…”

Section: Ponapensin; Cyclopenta[bc]benzopyran; Nf-κb; Aglaia Ponapensismentioning

confidence: 99%

Ponapensin, a cyclopenta[bc]benzopyran with potent NF-κB inhibitory activity from Aglaia ponapensis

Salim

Pawlus

Chai

et al. 2007

Bioorganic & Medicinal Chemistry Letters

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Two new compounds, a cyclopenta[bc]benzopyran, ponapensin (1), and an aglaialactone, 5,6-desmethylenedioxy-5-methoxy aglalactone (2), together with nine known compounds were isolated from the CHCl 3 soluble extract of the leaves and twigs of Aglaia ponapensis. Their structures were established by spectroscopic data interpretation. Ponapensin (1) exhibited significant NF-κB inhibitory activity in an Elisa assay, and was found to be more potent than the positive control rocaglamide. All of the compounds isolated were also tested in a panel of human cancer cell lines, with the known sterol E-volkendousin (3) and methyl rocaglate (aglafoline) found to be the only active substances. Keywords Ponapensin; Cyclopenta[bc]benzopyran; NF-κB; Aglaia ponapensisThe genus Aglaia Lour. (Meliaceae) consists of about 130 species, which are distributed mainly in the Indo-Malayan region, southern mainland China, and the Pacific Islands. 1 Since rocaglamide, the first cyclopenta[b]benzofuran, was isolated as a constituent of Aglaia elliptifolia, and was found to be active in an in vivo P388 model, 2 the phytochemical investigation of the genus Aglaia has led to the isolation of many related compounds. To date, about 60 naturally occurring cyclopenta[b]benzofuran type compounds, many of which exhibit insecticidal and antiproliferative activities, have been isolated from over 30 Aglaia species. 3,4 The cyclopenta[b]benzofurans and two structurally related groups, the cyclopenta[bc]-benzopyrans and benzo [b]oxepines, are considered characteristic secondary metabolites of the genus Aglaia, because they have been isolated only from this taxon. 3 The collective name "flavagline" has been proposed for these compounds because their mutual biogenetic origin has been postulated to be a flavonoid nucleus linked to a cinnamic acid moiety.

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Chemistry and Biological Activity of Rocaglamide Derivatives and Related Compounds in Aglaia Species (Meliaceae)

Cited by 130 publications

References 1 publication

Constituents of the leaves and stem bark of Aglaia foveolata

Constituents of the leaves and stem bark of Aglaia foveolata

Rocaglamide breaks TRAIL resistance in HTLV-1-associated adult T-cell leukemia/lymphoma by translational suppression of c-FLIP expression

Ponapensin, a cyclopenta[bc]benzopyran with potent NF-κB inhibitory activity from Aglaia ponapensis

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