Bioactive Flavaglines and Other Constituents Isolated from Aglaia perviridis

Abstract

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 (HT-29) 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 [Mo2(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 (ED50 0.0007 µM). The new compounds 2–4 were also active against this cell line, with ED50 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.

Investigation of Vietnamese plants for potential anticancer agents

“…The structure elucidation of the structurally interesting compound, perviridisin B ( 1 ), was based on extensive NMR data interpretation. Compound 1 exhibited 11 downfield proton signals in the 1 H-NMR spectrum, characteristic of a cyclopenta[ b ]benzopyran backbone, similar to the values described for previously reported compounds (Inada et al 2001; Pan et al 2013). In addition, the 1 H- and 13 C-NMR spectra showed characteristic signals that suggested the presence of a putrescinyl 4-hydroxytiglate residue linked by an amide bond to the cyclopenta[ b ]benzopyran skeleton.…”

“…In addition, the 1 H- and 13 C-NMR spectra showed characteristic signals that suggested the presence of a putrescinyl 4-hydroxytiglate residue linked by an amide bond to the cyclopenta[ b ]benzopyran skeleton. The C-10 epimer of 1 was also isolated in this study; however, this epimer showed no discernible biological activity (Pan et al 2013). Potent cytotoxicity against HT-29 cells with IC 50 values of less than 1 μM was observed for both perviridisin B ( 1 ) and elaeocarpucin C ( 32 ) (Pan et al 2012; Pan et al 2013).…”

“…In some cases promising lead compounds have been evaluated against biological targets other than those strictly germane to cancer chemotherapeutic drug discovery. The isolation procedures for the new compounds, perviridisin B ( 1 ), a cyclopenta[ b ]benzopyran analogue purified from Aglaia perviridis and elaeocarpucin C ( 32 ), a 16,23-epoxycucurbitacin derivative obtained from Elaeocarpus chinensis , were directed by LC/MS dereplication and cytotoxicity-guided fractionation using HT-29 human colon cancer cells (Pan et al 2012; Pan et al 2013). The structure elucidation of the structurally interesting compound, perviridisin B ( 1 ), was based on extensive NMR data interpretation.…”

“…Potent cytotoxicity against HT-29 cells with IC 50 values of less than 1 μM was observed for both perviridisin B ( 1 ) and elaeocarpucin C ( 32 ) (Pan et al 2012; Pan et al 2013). In addition, compound 1 showed no toxicity to CCD-112CoN normal human colon cells (Pan et al 2013). …”

Overexpression of eIF4F components in meningiomas and suppression of meningioma cell growth by inhibiting translation initiation

“…This characteristic may limit the distribution of silvestrol to the brain. Intriguingly, rocaglaol, a silvestrol-related compound lacking this ring, possesses antitumor activity and a synthetic analog of rocaglaol displays activity in drug-resistant breast carcinoma cells that overexpress MDR1 (Mi et al, 2006; Pan et al, 2013). The finding that the growth-suppressive effects of rocaglaol are also mediated by inhibiting protein translation indicates that the dioxanyl ring of silvestrol is dispensable for eIF4A inhibition (Ohse et al, 1996).…”