Eun-Kyoung Seo

New bioactive aromatic compounds from Vismia guianensis

Five benzophenones, vismiaguianones A-E, and two benzocoumarins, vismiaguianins A and B were isolated from the CHCl3 extract of the roots of Vismia guianensis by bioassay-directed fractionation using the DNA strand-scission assay and KB cell line. Of the isolates obtained, vismiaguianone B exhibited DNA strand-scission activity, whereas vismiaguianones D and E and vismiaguianin A were found to be significantly cytotoxic.

Cytotoxic prenylated flavanones from Monotes engleri.

From the leaves of Monotes engleri, five prenylated flavanones were isolated as constituents that displayed cytotoxic activity against several human cancer cell lines. There of these substances are novel, namely, 6-(1,1-dimethylallyl)naringenin, 6-(1,1-dimethylallyl)eriodictyol and 3-O-methyl-6-(1,1-dimethylallyl)-eriodictyol, with the other two active substances being the known flavanones, 6,8-diprenyleriodictyol and hiravanone. Additionally, two novel, but non-cytotoxic, biogenetically related flavanones were isolated, 6-[(2RS)-hydroxy-3-methyl-3-butenyl]-8-prenyleriodictyol and 5,4-dihydroxy-4,4-dimethyl-5-methyl-5H-dihydrofurano[2,3: 6,7]flavanone. The structures of the new compounds were determined by spectral analysis 1D- and 2D-NMR experiments.

Heat shock factor 1 inducers from the bark of Eucommia ulmoides as cytoprotective agents.

The barks of Eucommia ulmoides (Eucommiae Cortex, Eucommiaceae) have been used as a traditional medicine in Korea, Japan, and China to treat hypertension, reinforce the muscles and bones, and recover the damaged liver and kidney functions. Among these traditional uses, to establish the recovery effects on the damaged organs on the basis of phytochemistry, the barks of E. ulmoides have been investigated to afford three known phenolic compounds, coniferaldehyde glucoside (1), bartsioside (2), and feretoside (3), which were found in the family Eucommiaceae for the first time. The compounds 1–3 were evaluated for their inducible activities on the heat shock factor 1 (HSF1), and heat shock proteins (HSPs) 27 and 70, along with four compounds, geniposide (4), geniposidic acid (5), pinoresinol diglucoside (6), and liriodendrin (7), which were previously reported from E. ulmoides. Compounds 1–7 increased expression of HSF1 by a factor of 1.214, 1.144, 1.153, 1.114, 1.159, 1.041, and 1.167 at 3u2005μM, respectively. Coniferaldehyde glucoside (1) showed the most effective increase of HSF1 and induced successive expressions of HSP27 and HSP70 in a dose‐dependent manner without cellular cytotoxicity, suggesting a possible application as a HSP inducer to act as cytoprotective agent.

2,4-Bis(4-hydroxybenzyl)phenol inhibits heat shock transcription factor 1 and sensitizes lung cancer cells to conventional anticancer modalities.

Heat shock factor 1 (HSF1) is a transcription factor that regulates expression of heat shock protein (HSP) genes in response to stress. HSPs are expressed at high levels in a wide range of tumors. It has been reported that HSF1 and HSPs are associated closely in tumorigenesis. In the present study, a screen was performed using a luciferase reporter under the control of a heat shock element to find inhibitors of HSF1 activity, and 2,4-bis(4-hydroxybenzyl)phenol (1), isolated from the rhizomes of Gastrodia elata, was identified as an active compound. This substance effectively inhibited HSF1 activity and decreased levels of HSP27 and HSP70. Compound 1 induced the degradation of HSF1 protein through dephosphorylation of HSF1 on S326, which decreases HSF1 protein stability. In addition, 1 also induced growth arrest and apoptosis of NCI-H460 human lung cancer cells. Markers of apoptosis, such as cleaved PARP and cleaved caspase-3, were detected after treatment with 1. Furthermore, cotreatment with 1 and conventional anticancer modalities such as paclitaxel, cisplatin, or ionizing radiation potentiated their effects on lung cancer cells. These results suggest that inhibition of HSF1 by 1 may help overcome resistance to conventional anticancer modalities in HSF1-overexpressed cancer cells.

Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

Five new chalcones, 4,2,4-trihydroxy-3-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2,4-trihydroxy-3-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2,4-trihydroxy-3-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2,3-furano-4-hydroxy-4-methoxychalcone (4), and (±)-4-hydroxy-2,3-(2,3-dihydro-2-methoxyfurano)-4-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2,4-trihydroxy-3-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.

Induction of NAD(P)H: quinone reductase by rutaecarpine isolated from the fruits of Evodia rutaecarpa in the murine hepatic Hepa-1c1c7 cell line.

Rutaecarpine is a quinazolinocarboline alkaloid isolated from Evodia rutaecarpa (Juss.), which has been used in traditional Chinese medicine. The bioactivity-guided fractionation has led to the isolation of rutaecarpine from the extract of the fruits of E. rutaecarpa as the major component possessing NAD(P)H:quinone reductase (QR) activity. The activator protein-1 (AP-1), a transcriptional factor, in the antioxidant response element (ARE) region plays an important role in mediating induction of the target genes by xenobiotics, including chemopreventive agents. The present study demonstrates that rutaecarpine induces QR activity and gene expression by transactivation of AP-1. To study the induction of QR activity and AP-1-mediated QR gene expression by rutaecarpine, we performed enzyme and reporter gene assays. This compound markedly induced the enzyme activity and mRNA expression levels of QR in a dose-dependent manner. Using the luciferase reporter gene assay, a dose-dependent transactivation of AP-1-mediated luciferase expression was observed upon treatment of rutaecarpine. These results suggest that rutaecarpine induces QR gene expression and activity through an increase in AP-1 activation.

Synthesis and Biological Activity of Optically Active Phenylbutenoid Dimers

The total synthesis of optically active phenylbutenoid dimers 1, 3, and ent-3 is described. The key step to access optically active cyclohexene rings was achieved by Diels-Alder reaction of chiral acryloyloxazolinone 9 and phenylbetadiene 10.

Bioactive constituents of the family differocarpaceae

Abstract The family Dipterocarpaceae consists three subfamilies, Dipterocarpoideae, Monotoideae, and Pakaraimoideae. Plants of the largest subfamily, Dipteroearpoideae, are the sources of resveratrol oligomers (oligostilbenoids), sesquiterpenes, and triterpenes, in particular. Resveratrol oligomers, the most characteristic compound class of this subfamily, have been associated with several types of biological activity, such as antibacterial, antiviral, and cytotoxic effects. The two remaining subfamilies, Monotoideae and Pakaraimoideae, which are distinguished from the Dipterocarpoideae by the absence of resin, do not elaborate resveratrol oligomers. Compounds of the oligostilbenoid type seem worthy of more extensive biological investigation than has been the ease to date.

In vitro and in vivo evaluation of phenylbutenoid dimers as inhibitors of P-glycoprotein.

The expression of P-glycoprotein (P-gp), an ATP-dependent efflux transporter, is closely associated with the failure of chemotherapy and drug absorption. Two synthesized optically active phenylbutenoid dimers, 3S-(3,4-dimethoxyphenyl)-4R-{(E)-3,4-dimethoxystyryl}cyclohex-1-ene (1) and 3R-(3,4-dimethoxyphenyl)-4S-{(E)-3,4-dimethoxystyryl}cyclohex-1-ene (2), were tested for their P-gp inhibitory effects by measuring cellular accumulation and efflux of daunomycin in P-gp-overexpressed human breast cancer cells (MCF-7/ADR). Compound 2 significantly increased the accumulation of daunomycin (539%) and decreased the efflux of this compound (55.4%), and similar results were observed for 1. ATPase assays and Western blot analysis were performed to identify the mechanisms by which compounds 1 and 2 inhibit P-gp. In addition, changes in the pharmacokinetic profile of paclitaxel coadministered with 2 in rats were evaluated. Paclitaxel (25 mg/kg) when orally administered with 2 (5 mg/kg) improved its relative bioavailability by 185%. Compound 2 effectively improved cellular accumulation by reducing the efflux of daunomycin and significantly enhanced oral exposure to paclitaxel. Therefore, compound 2 may be useful for improving oral exposure and cellular availability of drugs that are also substrates of P-gp.

The dereplication of plant-derived natural products

Publisher Summary The dereplication of natural products is gaining greater importance in optimizing the process of natural product drug discovery as the pace of evaluating natural product extracts for their biological potential has increased. Over the years, as new technologies are introduced into analytical chemistry, they have been applied to detect known compounds before isolation and structure elucidation is initiated. Initially, chromogenic reagents were used to obtain information on the chemical classes of compounds found in natural product extracts. Though not very powerful in predictive nature as to the identity of compounds present, chemical class information was used in order to prioritize natural product extracts for subsequent isolation. The power of partially separating extracts with paper and thin-layer chromatographic techniques before subsequently spraying with chromogenic reagents, increased the ability of researchers to distinguish different classes of compounds from one another. TLC techniques were of major importance to many natural product drug discovery groups and are still widely used today. One of the most critical technologies to become available in the past decade and to advance the prioritization process is that of the computer. With the advent of small and powerful computers, information that is widely distributed and difficult to search, is now readily searchable by using any desired parameter such chemical, taxonomic, or pharmacological.