Arbutin derivatives from the buds of Vaccinium dunalianum and their MS/MS spectrometric fragmentations

Four arbutin derivatives were isolated from the buds of Vaccinium dunalianum in which 4-hydroxyphenyl-6′-(3''-O-β-D-glucopyranosyl-4''-hydroxycinnamoyl)-O-β-D-glucopyranoside (1) was a new compound. The structure of the new compound was determined on the basis of NMR and HR-ESI-MS data. All the arbutin derivatives were subjected to the MS/MS analyses from which the MS/MS spectrometric fragmentations were summarized.     

Chemical constituents from the stem bark of Acer tegmentosum

A new phenolic glycoside, 4-hydroxyphenylethyl-1-O-β-D-[6′-O-(4-hydroxybenzoyl)]-glucopyranoside (1) was isolated from the stem bark of Acer tegmentosum, along with seven known phenolic compounds (2–8). The structure of compound 1 was determined by spectral analyses, including HR-ESI-MS, 1D and 2D NMR (COSY, HMQC and HMBC) experiments. Compounds 3 and 4 were found in the family Aceraceae for the first time.     

Flavone C-glycosides from Coronilla varia

One new and 5 known flavone C-glycosides were isolated from leaves and stems of Coronilla varia. The new compound was shown to be isoorientin 2″-O-rhamnoside. The known compounds were isovitexin, isoorientin, isovitexin 4′-O-glucoside, isoorientin 4′-O-glucoside, and isoorientin 7-O-glucoside.     

5-Methyl ether flavone glucosides from the leaves of Bruguiera gymnorrhiza

Two new 5-methyl ether flavone glucosides (7,4′,5′-trihydroxy-5,3′-dimethoxyflavone 7-O-β-D-glucopyranoside and 7,4′-dihydroxy-5-methoxyflavone 7-O-β-D-glucopyranoside) were isolated from the leaves of Thai mangrove Bruguiera gymnorrhiza together with 7,3′,4′,5′-tetrahydroxy-5-methoxyflavone, 7,4′,5′-trihydroxy-5,3′-dimethoxyflavone, luteolin 5-methyl ether 7-O-β-D-glucopyranoside, 7,4′-dihydroxy-5,3′-dimethoxyflavone 7-O-β-D-glucopyranoside, quercetin 3-O-β-D-glucopyranoside, rutin, kaempferol 3-O-rutinoside, myricetin 3-O-rutinoside and an aryl-tetralin lignan rhamnoside. The structure of a lignan rhamnoside was found to be related to racemiside, an isolated compound from Cotoneaster racemiflora, and also discussed. Structure determinations were based on analyses of physical and spectroscopic data including 1D- and 2D-NMR.     

Chemical constituents from Nuxia congesta and their chemotaxonomic significance

A phytochemical investigation of the aerial parts of Nuxia congesta led to the isolation and identification of fifteen compounds, including a new flavonoid, nuxiacin (5-hydroxy-3,8-dimethoxy flavone-7-O-β-D-glycopyranoside) (1). The structure of the new compound was determined using various spectroscopic data including 1D and 2D NMR and mass spectroscopy. All compounds were isolated from N. congesta for the first time. The chemotaxonomic significance of the isolated compounds in the family Stilbaceae and order Lamiales are discussed herein.     

Bioactivity-guided isolation of antiproliferative compounds from Centaurea carduiformis DC

In this study, antiproliferative activity of methanol extract of Centaura carduiformis DC. subsp. carduiformis var. carduiformis DC (CC) was examined against Vero, HeLa and C6 cell lines in 1000 and 500 μg/mL concentrations using the BrdU ELISA assay. The CC root (CCR) has the most effective antiproliferative activity. The root extract was fractionated using various solvent and determined antiproliferative activities. Two new and two known flavonoids were isolated from CC roots. The isolated known compound of 7-O-β-d-glucopyranosyl-4′-methylapigenin and new compound of 7-O-β-d-6″-O-glucopyranosyl-6″-O-β-d-furanosylpinocembrin were isolated from the ethyl acetate fractions. However, wogonin and new compound of N-(pentyloxy(m-tolyl)methyl)acetamideisowogonin were obtained from chloroform fractions. The chemical structures of pure compounds were elucidated with different chemical and spectroscopic methods (IR, ¹H NMR, ¹³C NMR, HETCOR, COSY, GC-MS, etc.) and their antiproliferative activities were determined against Vero, HeLa and C6 cell lines. The IC₅₀ results showed that the compound 4 has the highest activity against Vero (250 μg/mL) and HeLa (735 μg/mL) cell lines than isolated other compounds from determined values.     

C-Glycosylflavones from Zea mays that inhibit insect development

A new C-glycosylflavone isolated from corn silk inhibits the growth and development of the corn earworm, Heliothis zea. This new compound was shown to be a 2″-O-α-l-rhamnosyl-6-C-(6-deoxy-xylo-hexos-4-ulosyl)luteolin. Also found co-occurring in corn silk were minor amounts of the corresponding 6-C-glycosylated analogs of chrysoeriol and apigenin.     

7′-hydroxy (−)-R-abscisic acid: A metabolite of feeding (−)-R-abscisic acid to Xanthium strumarium

Feeding of(±)-abscisic acid to leaves of Xanthium strumarium resulted in formation of a new metabolite. The compound was identified as 7′-hydroxy (−)-R-abscisic acid by high resolution mass spectrometry of its methyl ester and monoacetate, and by optical rotary dispersion. The numbering system for abscisic acid has been extended to include the exocyclic methyl groups. Feeding racemic [2-¹⁴C]abscisic acid to Xanthium leaves resulted in ca 20% conversion of the radiolabelled compound into the new metabolite. Evidence is presented that, in Xanthium, only the synthetic (−)-R-enantiomer of abscisic acid is hydroxylated at the 7′-position.     

A novel series of histamine H4 receptor antagonists based on the pyrido[3,2-d]pyrimidine scaffold: Comparison of hERG binding and target residence time with PF-3893787

In this work we describe the optimization of a lead compound based on the quinazoline template to give a new series of potent pyrido[3,2-d]pyrimidines as histamine H₄ receptor antagonists. The pyrido[3,2-d]pyrimidine ligands have significantly reduced hERG binding compared to clinical stage compound PF-3893787 while showing good affinities at the human and rodent histamine receptors. The receptor residence time of several of these new compounds was determined for the human H₄R and compared with JNJ7777120 and PF-3893787. The pyrido[3,2-d]pyrimidines showed residence times lower than JNJ7777120 but comparable to the residence time of PF-3893787. Overall, the pyrido[3,2-d]pyrimidines show an excellent in vitro profile that warrants their further investigation in relevant models of human disease.     

6-O-α-Sinuatosylaucubin from Verbascum sinuatum

From Verbascum sinuatum, besides aucubin, harpagide, 6-O-β-d-xylopyranosylaucubin and sinuatol (6-O- α-l-rhamnopyranosylaucubin), a new iridoid glycoside, sinuatoside, has been isolated and its structure elucidated as 6-O-(3-O-β-d-xylopyranosyl)α-d-galactopyranosyl aucubin on the basis of spectral data and chemical modifications. For the new disaccharide unit of the latter compound the name sinuatose is proposed.     

Flavonoide aus salix alba. Die struktur des Terniflorins und eines weiteren acylflavonoides

Eight flavonoids were isolated from the leaves of Salix alba. One, apigenin 7-O-(4-p-coumarylglucoside), is a new natural compound; another, terniflorin, the 6-isomer, is an artefact. The others are quercetin 3-O-glucoside, quercetin 3-O-rutinoside, isorhamnetin 3-O-glucoside, isorhamnetin 3-O-rutinoside and quercetin 7,′3-dimethylether 3-O-glucoside.     

3-O-feruloyl-4-O-caffeoylquinic acid from coffee beans

A new phenolic ester was isolated from unroasted robusta coffee beans (Coffea canephora) by HPLC. The isolated compound was identified as an ester of caffeic acid and ferulic acid with quinic acid (3-O-feruloyl-4-O-caffeoylquinic acid) using ¹H NMR and mass spectroscopy.     

3,4,8,9,10-Pentahydroxy-dibenzo[b,d]pyran-6-one from Tamarix nilotica

A new natural product, 3,4,8,9,10-pentahydroxy-dibenzo-[b,d]pyran-6-one was isolated from the flowers of Tamarix nilotica which also contains the known compound ellagic acid, 2,3,7,8-tetrahydroxy [1]benzopyrano[5,4,3-cde][1]benzopyran-5,10-dione. The structure of the new compound was determined by chemical and spectroscopic methods. The ¹³C MNR spectrum of ellagic acid was recorded and assigned.     

Flavonoid glucuronides from Picria fel-terrae

Three flavonoid glucuronides are reported from a n-BuOH extract of Picria fel-terrae (Scrophulariaceae). The structures were established by UV, one- and two-dimensional NMR and mass spectrometry as apigenin 7-O-β-glucuronide, luteolin 7-O-β-glucuronide and apigenin 7-O-β-(2″-O-α-rhamnosyl)glucuronide, the latter one being a new compound.     

A furostanol glucuronide from Solanum lyratum

A new furostanol glucuronide and three known glycosides, SL-O, aspidistrin and methyl proto-aspidistrin, were isolated from the fresh immature berries of Solanum lyratum. The structure of the new compound was characterized as 26-O-β-D-glucopyranosyl-(22ξ,25R-3β,22,26-trihydroxyfurost-5-ene 3-O-α-L-rhamnopyranosyl-(1 → 2)-[β-D-glucopyranosyl-(1 → 3)]-β-D-glucuronopyranoside.     

Discovery of a pyrazolo[1,5-a]pyrimidine derivative (MT-3014) as a highly selective PDE10A inhibitor via core structure transformation from the stilbene moiety

We have developed a new class of PDE10A inhibitor, a pyrazolo[1,5-a]pyrimidine derivative MT-3014 (1). A previous compound introduced was deprioritized due to concerns for E/Z-isomerization and glutathione-adduct formation at the core stilbene structure. We discovered pyrazolo [1,5-a] pyrimidine as a new lead scaffold by structure-based drug design utilizing a co-crystal structure with PDE10A. The lead compound was optimized for in vitro activity, solubility, and selectivity against human ether-á-go-go related gene cardiac channel binding. We observed that MT-3014 shows excellent efficacy in rat conditioned avoidance response test and suitable pharmacokinetic properties in rats, especially high brain penetration.     

Isomerization of 1-O-Indol-3-Ylacetyl-β-d-Glucose : Enzymatic Hydrolysis of 1-O, 4-O, and 6-O-Indol-3-YlacetyL-β-d-Glucose and the Enzymatic Synthesis of Indole-3-Acetyl Glycerol by a Hormone Metabolizing Complex

The first compound in the series of reactions leading to the ester conjugates of indole-3-acetic acid (IAA) in kernels of Zea mays sweet corn is the acyl alkyl acetal, 1-O-indol-3-ylacetyl-β-d-glucose (1-O-IAGlu). The enzyme catalyzing the synthesis of this compound is UDP-glucose:indol-3-ylacetate glucosyl-transferase (IAGlu synthase). The IAA moiety of the high energy compound 1-O-IAGlu may be enzymatically transferred to myo-inositol or to glycerol or the 1-O-IAGlu may be enzymatically hydrolyzed. Alternatively, nonenzymatic acyl migration may occur to yield the 2-O, 4-O, and 6-O esters of IAA and glucose. The 4-O and 6-O esters may then be enzymatically hydrolyzed to yield free IAA and glucose. This work reports new enzymatic activities, the transfer of IAA from 1-O-IAGlu to glycerol, and the enzymecatalyzed hydrolysis of 4-O- and 6-O-IAGlu. Data is also presented on the rate of non-enzymatic acyl migration of IAA from the 1-O to the 4-O and 6-O positions of glucose. We also report that enzymes catalyzing the synthesis of 1-O-IAGlu and the hydrolysis of 1-O, 4-O, and 6-O-IAGlu fractionate as a hormone metabolizing complex. The association of synthetic and hydrolytic capabilities in enzymes which cofractionate may have physiological significance.     

Isocarlinoside,a di-C-glycosylflavone from Lespedeza capitata

Six di-C-glycosylflavones isolated from Lespedeza capitata leaves were identified as schaftoside, neoschaftoside, isoschaftoside, carlinoside, neocarlinoside and a new natural compound: isocarlinoside (6-C-α-l-arabinopyranosyl-8-C-β-d-glucopyranosylluteolin).     

Synthesis and evaluation of the cell cycle arrest and CT DNA interaction properties of 4β-amino-4′-O-demethyl-4-deoxypodophyllotoxins

A series of 4β-amino-4′-O-demethyl-4-deoxypodophyllotoxin derivatives were synthesized, and their cytotoxicities against several human cancer cell lines, including HepG2, A549, HeLa and HCT-8 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4β-N-(4-Nitrophenyl piperazinyl)-4′-O-demethyl-4-deoxypodophyllotoxin (11) was found to be the most potent synthesized compound in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of cdc2, cyclin B1, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form.     

2-O-Methylconfluentinsäure: Ein neues depsid aus Lecidea fuscoatra

The lichen, Lecidea fuscoatra contains the new depside 2-O-methylconfluentinic acid. The structure of this compound follows front spectroscopical data and hydrolysis of its methyl ester to give olivetonic acid dimethyl ether and 2-O-methyl olivetol carboxylic acid.