Terpenoids and a Flavonoid Glycoside from <i>Acacia pennata</i> Leaves as Hedgehog/GLI-Mediated Transcriptional Inhibitors

Rifai, Yusnita; Arai, Midori A.; Koyano, Takashi; Kowithayakorn, Thaworn; Ishibashi, Masami

doi:10.1021/np1000818

Cited by 58 publications

(49 citation statements)

References 25 publications

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“…Compound 2, obtained as a white powder, was assigned to have the molecular formula C 15 , thus suggesting the replacement of the alcohol group in 8 by a aldehyde group in the new compound 2. This conclusion was also supported by the apparent downshifted C-9 (D 9.3 ppm), caused by the deshielding effect of the aldehyde functionality.…”

Section: )mentioning

confidence: 99%

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Drimane Sesquiterpenoids from the Mangrove-Derived Fungus Aspergillus ustus

et al. 2011

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Fungi from mangrove have attracted much attention for their unique living conditions of wave-energy tidal mudflats, high moisture level, high salt concentration and lack of oxygen.1) This fungal group has been widely recognized as rich source of active secondary metabolites.2,3) As part of our ongoing search for novel bioactive compounds from microorganisms isolated from unusual or specialized ecological niches, 4-6) the culture extract of a fungus strain (Aspergillus ustus), isolated from the rhizosphere soil of the mangrove Acrostichum aureurm grown in Guangxi Province of China, showed cytotoxic activity against P388 (mice lymphocytic leukemia) cell line. The chemical composition research on the EtOAc extract of the A. ustus fermentation led us to identify five new drimane sesquiterpenes (1-5) together with 14 known analogues (Fig. 1).1,7-12) Herein, we report the structural elucidations and cytotoxic activities of these metabolites against P388, HL-60 (human promyelocytic leukemia cells), K562 (human erythromyeloblastoid leukemia cells) and BEL-7402 (human hepatoma cells).Compound 1 was obtained as a white powder. The molecular formula was determined as C 16 H 28 O 3 on the basis of its high resolution-electrospray ionization-mass spectra (HR-ESI-MS) peak at m/z 291.1930 [MϩNa] ϩ (Calcd for C 16 C-NMR (distortionless enhancement by polarization transfer (DEPT)) spectrum (Table 2) displayed 16 carbon resonances, assignable to five methyls, four methylenes, three methines and four quaternary carbons. Apart from one degree of unsaturation occupied by a double bond, the remaining two degrees of unsaturation required 1 to contain a bicyclic core ring system. The aforementioned data implied that 1 was a drimane sesquiterpense.13) The NMR resonances were similar to those reported for albrassitriol (20), but replacing one of the OHs by a methoxyl group.13) The structure of 1 was further confirmed by 1 H-1 H correlation spectroscopy (COSY) and heteronuclear multiple bond connectivity (HMBC) correlations (Fig. 2). The connection of C-11 and C-9 was determined by the HMBC correlations from H-11 to C-8 and C-10, and the location of -OCH 3 at C-6 was deduced via a correlation between the methoxy protons and C-6.The relative configuration of 1 was determined by the nuclear Overhauser effect spectroscopy (NOESY) spectrum. Correlations between H-13 and H-1b (eq) and between H-5 and H-1a (ax) suggested a trans-fused decalin nucleus.1) The correlation between H-5 and 6-OCH 3 indicated the configu- Five new drimane sesquiterpenes (1-5) together with 14 known analogues (6-19) were isolated from laboratory cultures of a mangrove-derived fungus Aspergillus ustus. Their structures were established by spectroscopic methods and antitumor activities were evaluated by sulforhodamine B (SRB) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods.

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confidence: 99%

“…The molecular formula was established as C 15 (Fig. 2) represented three structural moieties, C-1 to C-3, C-6(OH) to C-7(OH) and C-11(OH) to C-11.…”

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confidence: 99%

Drimane Sesquiterpenoids from the Mangrove-Derived Fungus Aspergillus ustus

et al. 2011

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“…Bioassay-guided fractionation of Zizyphus cambodiana extract led to the isolation of three active pentacyclic triterpenes, including colubrinic acid (15). 39) Potent inhibitors were isolated from Acacia pennata, 40) Adenium obesum 41) and Excoecaria agallocha. 42 We recently found a new type of Hh inhibitor from Excoecaria agallocha.…”

Section: Discovery Of Hh Signaling Inhibitors From Natural Productsmentioning

confidence: 99%

Approaches to Neural Stem Cells and Cancer Cells Based on Natural Products

Arai

2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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We have developed "protein-and cell-based screen methods" for the isolation of new natural products. By using VDR (vitamin D receptor) immobilized magnetic beads, two new natural products were isolated rapidly. To find inhibitors of Hes1 protein, which is one of the important transcriptional factors in neural stem cells, a Hes1 dimer plate assay was developed, and then first Hes1 dimer inhibitors were found from our natural products library. As a "cell-based screen method," a reporter gene assay for screening Hh (hedgehog) signaling inhibitors was constructed. New Hh signaling inhibitors were isolated from our natural extracts library. We evaluated their Hh inhibitory activity in Hh related protein synthesis and cytotoxicity against cancers, in which Hh signaling is aberrantly activated. In addition to the naturally made compounds library (extracts library), "small molecules based on natural products" were synthesized. The total synthesis of Melleumin A, B, which were isolated by our group, was achieved. From their synthetic derivatives, inhibitors of the Wnt signal, which has been reported to cause colon cancers, were discovered. Moreover, flavanone and chromone were selected as natural product scaffolds. Many flavonoids and chromones with diverse heterocyclic units were constructed using our efficient synthetic method.

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“…The direct association of GLI with a specific binding site (5’-GACCACCCA-3’) in the promoter region of the target gene has been reported to contribute to pancreatic and prostate cancer cells 3 . We previously reported Hedgehog/GLI inhibitors from various plants 4– 6 . We also isolated five lignan s (( 8 R* ,8’R*)-9-hydroxy-3,4-dimethoxy-3’,4’-methylenedioxy-9,9’-epoxylignan, kusunokinin, haplomyrfolol, dihydroclusin) including a new epoxylignan dmeo from Piper nigrum using the immobilization of GLI-GST on carboxylic acid magnetic dynabeads.…”

Section: Introductionmentioning

confidence: 99%

Characterization and stability evaluation of nanoencapsulated epoxylignans

et al. 2018

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3',6-dimethoxy-3'',4''-(methylenedioxy)-2,5-epoxylignan-4'-ol (DMEO), an epoxylignan isolated from Piper nigrum, has currently captured attention for its potential antitumor effect. However, low stability is limiting its therapeutic application. The application of nanocapsulation would be the main strategy for overcoming this problem. DMEO-loaded nanocapsules were prepared by an emulsion-diffusion method using Eudragit RL 100 (at concentrations of 1, 1.5 and 2%) and polyvinyl alcohol. As the polymer content increased, the encapsulation efficiency and mean particle size also increased. After 6 months of storage at 25°C (0% RH), no crystalline peaks were observed in the diffraction patterns of all nanocapsules, thereby suggested that the physical stability of nanoencapsulated DMEO was not affected by the concentration ratio of the polymer−stabilizer combinations.

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Terpenoids and a Flavonoid Glycoside from Acacia pennata Leaves as Hedgehog/GLI-Mediated Transcriptional Inhibitors

Cited by 58 publications

References 25 publications

Drimane Sesquiterpenoids from the Mangrove-Derived Fungus Aspergillus ustus

Drimane Sesquiterpenoids from the Mangrove-Derived Fungus Aspergillus ustus

Approaches to Neural Stem Cells and Cancer Cells Based on Natural Products

Characterization and stability evaluation of nanoencapsulated epoxylignans

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