Myoung Chong Song

Anthracyclines, such as doxorubicin, are effective anticancer drugs composed of a tetracyclic polyketide aglycone and one or more deoxysugar moieties, which play a critical role in their biological activity. A facile one-pot combinatorial biosynthetic system was developed for the generation of a range of glycosylated derivatives of anthracyclines. Cocultivation of Streptomyces venezuelae mutants producing two anthracycline aglycones with eight different nucleotide deoxysugar-producing S. venezuelae mutants that coexpress a substrate-flexible glycosyltransferase led to the generation of 16 aklavinone or ε-rhodomycinone glycosides containing diverse deoxysugar moieties, seven of which are new. This demonstrates the potential of the one-pot combinatorial biosynthetic system based on cocultivation as a facile biological tool capable of combining diverse aglycones and deoxysugars to generate structurally diverse polyketides carrying engineered sugars for drug discovery and development.

Milbemycins, produced from Streptomyces hygroscopicus subsp. aureolacrimosus and Streptomyces bingchenggensis, are 16-membered macrolides that share structural similarity with avermectin produced from Streptomyces avermitilis. Milbemycins possess strong acaricidal, insecticidal, and anthelmintic activities but low toxicity. Due to the high commercial value of the milbemycins and increasing resistance to the avermectins and their derivatives, it is imperative to develop an efficient combinatorial biosynthesis system exploiting an overproduction host strain to produce the milbemycins and novel analogs in large quantities. The respective replacement of AveA1 and AveA3 (or module 7 in AveA3) of the avermectin polyketide synthase (PKS) in the avermectin high-producing strain S. avermitilis SA-01 with MilA1 and MilA3 (or module 7 in MilA3) of the milbemycin PKS resulted in the production of milbemycins A3, A4, and D in small amounts and their respective C5-O-methylated congener milbemycin...

The S-adenosyl-l-methionine-dependent O-methyltransferases TylE and TylF catalyze the last two methylation reactions in the tylosin biosynthetic pathway of Streptomyces fradiae. It has long been known that the TylE-catalyzed C2‴-O-methylation of the 6-deoxy-d-allose bound to demethylmacrocin or demethyllactenocin precedes the TylF-catalyzed C3‴-O-methylation of the d-javose (C2‴-O-methylated 6-deoxy-d-allose) attached to macrocin or lactenocin. This study reveals the unexpected substrate promiscuity of TylE and TylF responsible for the biosynthesis of d-mycinose (C3‴-O-methylated d-javose) in tylosin through the identification of a new minor intermediate 2‴-O-demethyldesmycosin (2; 3‴-methyl-demethyllactenocin), which lacks a 2‴-O-methyl group on the mycinose moiety of desmycosin, along with 2‴-O-demethyltylosin (1; 3‴-methyl-demethylmacrocin) that was previously detected from the S. fradiae mutant containing a mutation in the tylE gene. These results unveil the unique substrate fle...

The aerial parts of Chrysanthemum coronarium L. were extracted with MeOH, and the extract was partitioned using EtOAc, n-BuOH, and . The repeated column chromatography of the EtOAc and n-BuOH fractions gave two terpenes, phytol and 8-hydroxylinalol 8-O--D-glucopyranoside, identified by several spectral analyses, including NMR and MS. This paper is the first report on the isolation of these terpenes from Chrysanthemum coronarium L.

The MeOH extracts obtained from whole plant of Trigonotis peduncularis Benth. were solvent fractionated using EtOAc, n-BuOH and water, successively. The EtOAc and n-BuOH fractions gave four flavonol glycosides through application of silica gel and octadecyl silica gel (ODS) column chromatographies. The chemical structures of the flavonol glycosides were determined by the interpretation of several spectral data including 2D-NMR as kaempferol-3-O-β-D-glucopyranoside (astragalin, 1), kaempferol-3-O-α-L-rhamnopyranosyl (16)-β-D-glucopyra-noside (nicotiflorin, 2), quercetin-3-O-α-L-rhamnopyranosyl(16)-β-D-glucopyranoside (rutin, 3), quercetin-3-O-β-D-glucopyranoside (isoquercitrin, 4). The flavonoids have been first isolated from this plant. Nicotiflorin (100 µg/ ml) showed 68.3Û1.2% of the inhibitory effect on hACAT1(human Acyl CoA: cholesterol transferase 1) activity.

ABSTRACT The aerial parts of Chrysanthemum coronarium were extracted in MeOH, and the extract was partitioned using EtOAc, n-BuOH and H2O. The repeated column chromatography of EtOAc fraction gave four sterols, whose chemical structures were identified as stigmast-4-en-6-o1-3-one (1), stigmast-4- en-6-ol-3-one (2), which have been so far reported only in the aquatic plants and were isolated for the first time from the land plants, -sitosterol (3) and daucosterol (4) based on several spectral data including gCOSY, gHSQC, gHMBC and comparison of the data with those of literature. And the repeated column chromatography of EtOAc and n-BuOH fractions gave nine polyacetylens, which were identified as 2-[(lZ,4Z)-5-methylsulfinyl-2-pentyn-4-enyliden]-1,6- dioxaspiro[4,4]non-3-ene (5), 2-[(IE,4Z)-5-methylsulfinyl-2-pentyn-4-enyliden]- 1,6-dioxaspiro[4,4]non-3-ene (6), 2-[lZ-2,4-dipentyn-6-methyliden]-1,6-dioxaspiro [4,4]non-3-ene (7), 2-[lE-2,4-dipentyn-6-methyliden]-1,6-ioxaspiro[4,4]non-3- ene (8), 2-[lE-2,4-dipentyn-6-methyliden]-1,6-dioxaspiro[4,5]non-3-ene (9), 2-[lZ- 2,4-dipentyn-6-methylidene]-1,6-dioxaspiro[4,4]non-3,7-dien-9-ol (10), 2-[lE-2, 4-dipentyn-6-methyliden]-1,6-dioxaspiro[4,4]non-3,7-dien-9-ol (11), 2-[lE-2,4- dipentyn-6-methyliden]-1,6-dioxaspiro[4,4] non-3,7-dien-9-ol (12) and 2-[1Z- 2,4-dipentyn-6-methyliden ]-1,6-dioxaspiro[4,4]non-3,7-dien-9-o1 (13). Some of them showed the inhibitory effect on the activity of ACAT (Acyl-CoA: cholesterol acyltransferase), the catalyzing enzymes of the intracellular esterification of cholesterol, and FPTase (Farnesyl-protein transferase), the farnesylation enzymes for Ras protein in charge of cancer promotion, PLT aggregation, and the growth of HUVEC (Human umbilical vascular endothelial cell) or A549 cells.

One of the major challenges in computational approaches to drug design is the accurate prediction of the binding affinity of novel biomolecules. In the present study an automated procedure which combines docking and 3D-QSAR methods was applied to several drug targets. The developed receptor-based 3D-QSAR methodology was tested on several sets of ligands for which the three-dimensional structure of the target protein has been solved--namely estrogen receptor, acetylcholine esterase and protein-tyrosine-phosphatase 1B. The molecular alignments of the studied ligands were determined using the docking program AutoDock and were compared with the X-ray structures of the corresponding protein-ligand complexes. The automatically generated protein-based ligand alignment obtained was subsequently taken as basis for a comparative field analysis applying the GRID/GOLPE approach. Using GRID interaction fields and applying variable selection procedures, highly predictive models were obtained. It ...

This study was performed to characterize natural CLnA isomer production by Bifidobacterium breve LMC520 of human origin in comparison to conjugated linoleic acid (CLA) production. B. breve LMC520 was found to be highly active in terms of CLnA production, of which the major portion was identified as cis-9,trans-11,cis-15 CLnA isomer by GC-MS and NMR analysis. B. breve LMC520 was incubated for 48 h using MRS medium (containing 0.05% L-cysteine · HCl) under different environmental conditions such as atmosphere, pH, and substrate concentration. The high conversion rate of α-linolenic acid (α-LNA) to CLnA (99%) was retained up to 2 mM α-LNA, and the production was proportionally increased nearly 7-fold with 8 mM by the 6 h of incubation under anaerobic conditions at a wide range of pH values (between 5 and 9). When α-LNA was compared with linoleic acid (LA) as a substrate for isomerization by B. breve LMC520, the conversion of α-LNA was higher than that of LA. These results demonstrated that specific CLnA isomer could be produced through active bacterial conversion at an optimized condition. Because many conjugated octadecatrienoic acids in nature are shown to play many positive roles, the noble isomer found in this study has potential as a functional source.

ABSTRACT Two new iridoids were isolated and identified to three known ones, namely, loganic acid (2), sweroside (3), and 7-O-tigloylsecologanol (4), from the stems of Viburnum erosum. Dried stems of V. erosum were extracted with 80% methanol (MeOH), and the concentrated extract was partitioned successively with ethyl acetate (EtOAc), n-butyl alcohol (n-BuOH), and H2O. Five compounds were isolated after repeated silica gel (SiO2), octadecyl SiO2 (ODS), and Sephadex LH-20 column chromatography of the EtOAc fraction. The chemical structures of the compounds were determined based on spectroscopic data from 1H- and 13C-NMR, DEPT, and 2D-NMR (gCOSY, gHSQC, gHMBC) data. The new iridoids were identified as 3,7-dihydroxy-8-methyl-cyclopenta[c]pyran-4-carboxylic acid (1) and rel-(1S,5R,9S)-9-ethenyl-1-(β-D-glucopyrinosyloxy)-5,9-dihydro-5-{2-[(2-methylbut-2-enoyl)oxy]ethyl}-1H-pyran-4-carboxylic acid (5) and named viburnin and epi-7-O-tigloylsecologanolic acid, respectively. This is the first report of the isolation of these five iridoids from V. erosum.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ixeris dentata formaalbiflora was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc,n-BuOH and H2O. Eight sesquiterpenes were isolated through repeated silica gel and octadecyl silica gel (C18, ODS) column chromatography of the EtOAc andn-BuOH fractions. Physicochemical analysis using NMR, MS and IR revealed the chemical structures of the sesquiterpenes, which were zaluzanin (1), 9a-hydroxyguaian-4(15), 10(14), 11(13)-triene-6, 12-olide (2), 3β-O-β-D-glucopyranosyl-8β-hydroxyguaian-4(15), 10(14)-diene-6,12-olide (3), 3-O-β-D-glucopyranosyl-8β-hydroxyguauan-10(14)-ene-6,12-olide (4), ixerinM (5), glucozaluzanin C (6), crepiside I (7), and ixerin D (8). This is the first time that these sesquiterpene lactones have been isolated from this plant. Compounds1, 2 and7 revealed relatively high cytotoxicities on human colon carcinoma cell and lung adenocarcinoma cell, while compounds5 and7 showed acyl-CoA: cholesterol acyltransferase (ACAT) inhibitory activity.

A new lignan glycoside, 6-acetyl-1-[1,3-(4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinyl)-beta-d-fructofuranosyl]-alpha-d-glucopyranoside (1), named impecyloside, was isolated from the rhizomes of Imperata cylindrica. The structure of the compound was determined by spectroscopic data including FABMS, UV, IR, 1H NMR and 13C NMR (DEPT) and 2D NMR (COSY, HSQC, HMBC).

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The aerial parts of Chrysanthemum coronarium L. were extracted with MeOH, and the concentrated extract was partitioned using EtOAc, n-BuOH, and H2O, successively. Repeated column chromatography of the EtOAc and n-BuOH fractions gave a new heterocycle, 5,5′-dibuthoxy-2,2′-bifuran (1) along with five known compounds: methyl trans-ferulate (2), prunasin (3), sambunigrin (4), pterolactam (5), and adenosine (6), which were identified by several spectroscopic methods including NMR and MS. This paper is the first report on the isolation of these compounds from C. coronarium L. The IC50 values of compound 1 for human Acyl-CoA:cholesterol acyltransferase (hACAT)-1 and hACAT-2 were 0.16 mM and 0.19 mM, respectively. Compound 2 inhibited low-density lipoprotein (LDL) oxidation with an IC50 value of 7.7 μM.

Repeated silica gel and octadecyl silica gel (ODS) column chromatography of the aerial parts of Artemisia princeps PAMPANINI (Sajabalssuk) led to the isolation of a new sesquiterpenoid, 3-((S)-2-methylbutyryloxy)-costu-1(10),4(5)-dien-12,6 alpha-olide (2), along with two previously reported sesquiterpenoids: 8 alpha-angeloyloxy-3beta,4 beta-epoxy-6 beta H,7 alpha H,8 beta H-guaia-1(10),11(13)-dien-12,6 alpha-olide (1, carlaolide B) and 3beta,4 beta-epoxy-8 alpha-isobutyryloxy-6 beta H,7 alpha H,8 beta H-guaia-1(10),11(13)-dien-12,6 alpha-olide (3, carlaolide A). The structure of compound 2 was elucidated by spectroscopic data analysis, including one dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) experiments. Of the isolates, compound 2 exhibited potent cytotoxicity against human cervix adenocarcinoma cells and induced apoptosis.

The 80% aqueous MeOH extracts from the root of Angelica dahurica, found to inhibit the activities of GABA degradative enzymes GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), were fractionated using EtOAc, n-BuOH and H2O. Repeated column chromatography for the EtOAc and n-BuOH fractions led to the isolation of two new coumarins, oxypeucedanin hydrate-3″-butyl ether and isopraeroside IV along with six known coumarins, isoimperatorin, imperatorin, phellopterin, oxypeucedanin hydrate, nodakenin and 3′-hydroxymarmesinin, and two polyacetylenes, falcarindiol and octadeca-1,9-dien-4,6-diyn-3,8,18-triol. Of the isolated pure compounds, imperatorin and falcarindiol inactivated the GABA-T activities in both time- and concentration-dependent manners. The kinetic studies showed that imperatorin and falcarindiol reacted with the GABA-T with a second-order rate constant of 2.3 ± 0.2 mm−1 min−1 and 1.5 ± 0.1 mm−1 min−1, respectively. It is postulated that imperatorin and falcarindiol are able to elevate the neurotransmitter GABA levels in the central nervous system by an inhibitory action on the GABA degradative enzyme GABA-T. Copyright © 2005 John Wiley & Sons, Ltd.

Campesterol, a plant sterol in nature, is known to have cholesterol lowering and anticarcinogenic effects. Since angiogenesis is essential for cancer, it was surmised that an antiangiogenic effect may be involved in the anticancer action of this compound. This study investigated the effect of campesterol on basic fibroblast growth factor (bFGF)-induced angiogenesis in vitro in human umbilical vein endothelial cells (HUVECs) and an in vivo chorioallantoic membrane (CAM) model. Campesterol isolated from an ethylacetate fraction of Chrysanthemum coronarium L. showed a weak cytotoxicity in non-proliferating HUVECs. Within the non-cytotoxic concentration range, campesterol significantly inhibited the bFGF-induced proliferation and tube formation of HUVECs in a concentration-dependent manner, while it did not affect the motility of HUVECs. Furthermore, campesterol effectively disrupted the bFGF-induced neovascularization in chick chorioallantoic membrane (CAM) in vivo. Taken together, these results support a potential antiangiogenic action of campesterol via an inhibition of endothelial cell proliferation and capillary differentiation. Copyright © 2007 John Wiley & Sons, Ltd.

The fruits of Cornus kousa Burg. were extracted with 80% aqueous MeOH, and the concentrated extract partitioned with EtOAc, n-BuOH and H2O. Six lignans were isolated from the EtOAc fraction through repeated silica gel, ODS and Sephadex LH-20 column chromatographies. From the physico-chemical data, including NMR, MS and IR, the chemical structures of the compounds were determined to be (+)-pinoresinol (1), (-)-balanophonin (2), (+)-laricresinol (3), erythro-guaiacylglycerol-β-coniferyl aldehyde ether (4), threo-guaiacylglycerol-β-coniferyl aldehyde ether (5) and dihydrodehydrodiconiferyl alcohol (6), which were isolated for the first time from this plant. Most of these compounds showed cytotoxicity against human colon carcinoma (HCT-116) and human hepatocellular carcinoma (HepG2) cell lines in vitro, with IC50 values ranging from 19.1 to 71.3 μg/mL.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.