Coumarins from Malaysian Micromelum minutum

In a continuation of our study of the Rutaceae, detailed chemical investigation on Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia gave four new coumarins. The structures of the coumarins have been fully characterised by spectroscopic methods as 3",4"-dihydrocapnolactone 1, 2',3'-epoxyisocapnolactone 2, 8-hydroxyisocapnolactone-2',3'-diol 3 and 8-hydroxy-3",4"-dihydrocapnolactone-2',3'-diol 4.     

Synthesis, spectroscopic characterization and biological activity on newly synthesized copper(II) and nickel(II) complexes incorporating bidentate oxygen-nitrogen hydrazone ligands

We report the synthesis of the hydrazone ligands, 1-(phenyl-hydrazono)-propan-2-one (PHP), 1-(p-tolyl-hydrazono)-propan-2-one (THP), 1-[(4-chloro-hydrazono)]-propan-2-one (CHP), and their Ni(II) and Cu(II) metal complexes. The structure of the ligands and their complexes were investigated using elemental analysis, magnetic susceptibility, molar conductance and spectral (IR, UV, and EPR) measurements. IR spectra indicate that the free ligands exist in the hydrazo-ketone rather than azo-enol form in the solid state. Also, the hydrazo-NH exists as hydrogen bonded to the keto-oxygen either as intra or as intermolecular hydrogen bonding. In all the studied complexes, all ligands behave as a neutral bidentate ligands with coordination involving the hydrazone-nitrogen and the keto-oxygen atoms. The magnetic and spectral data indicate a square planar geometry for Cu²⁺ complexes and an octahedral geometry for Ni²⁺ complexes. The ligands and their metal chelates have been screened for their antimicrobial activities using the disc diffusion method against the selected bacteria and fungi. They were found to be more active against Gram-positive than Gram-negative bacteria. It may be concluded that the antimicrobial activity of the compounds is related to cell wall structure of bacteria.Protonation constant of (PHP) ligand and stability constants of its Cu²⁺ and Ni²⁺ complexes were determined by potentiometric titration method in aqueous solution at ionic strength of 0.1 M sodium nitrate. It has been observed that the hydrazone ligand (PHP) titrated here has one protonation constant. The divalent metal ions Cu²⁺ and Ni²⁺ form with (PHP) 1:1 and 1:2 complexes. The insolubility of (THP) and (CHP) ligands in aqueous medium does not permit the determination of their protonation constants and formation constants of the corresponding complexes in aqueous solution.     

Inhibitory effect on NO production of phenolic compounds from Myristica fragrans

Three new phenolics: ((7S)-8'-(benzo[3',4']dioxol-1'-yl)-7-hydroxypropyl)benzene-2,4-diol (1), ((7S)-8'-(4'-hydroxy-3'-methoxyphenyl)-7-hydroxypropyl)benzene-2,4-diol (2) and ((8R,8'S)-7-(4-hydroxy-3-methoxyphenyl)-8'-methylbutan-8-yl)-3'-methoxybenzene-4',5'-diol (3), along with four known compounds (4-7) were isolated from the seeds of Myristica fragrans. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW264.7 cells.     

Flavonoids, including an unusual flavonoid-Mg2+ salt, from roots of Cudrania cochinchinensis

Four flavonoids with 2',4'-di-oxygenated B-rings, cochinchinol A (1), cochinchinol B (2), (2R,3R)-4',7-dihydroxy-2',5-dimethoxydihydroflavonol (3), 4',7-dihydroxy-2',5-dimethoxyflavonol (4), along with 11 known compounds, were isolated from an ethanolic extract of the roots of Cudrania cochinchinensis. Their structures were elucidated by chemical and spectroscopic methods. Cochinchinol A (1) and cochinchinol B (2) have two hitherto unprecedented flavonol salt structures in natural product chemistry. Cytotoxic activities were evaluated against several different cell lines.     

Biotransformation of myrislignan by rat liver microsomes in vitro

Myrislignan (1), erythro-(1R,2S)-2-(4-allyl-2,6-dimethoxyphenoxyl)-1-(4-hydroxy-3-methoxyphenyl) propan-1-ol, is a major acyclic neolignan in seeds of Myristica fragrans. Studies have suggested that myrislignan may deter feeding activity, but little is known about its metabolism. We investigated the biotransformation of myrislignan by rat liver microsomes in vitro. Seven metabolites were produced by liver microsomes from rats pre-treated with sodium phenobarbital. These were identified, using spectroscopic methods, as myrislignanometins A-G (2-8), respectively.     

Crystal structure of the 2'-5' RNA ligase from Thermus thermophilus HB8

The 2'-5' RNA ligase family members are bacterial and archaeal RNA ligases that ligate 5' and 3' half-tRNA molecules with 2',3'-cyclic phosphate and 5'-hydroxyl termini, respectively, to the product containing the 2'-5' phosphodiester linkage. Here, the crystal structure of the 2'-5' RNA ligase protein from an extreme thermophile, Thermus thermophilus HB8, was solved at 2.5A resolution. The structure of the 2'-5' RNA ligase superimposes well on that of the Arabidopsis thaliana cyclic phosphodiesterase (CPDase), which hydrolyzes ADP-ribose 1",2"-cyclic phosphate (a product of the tRNA splicing reaction) to the monoester ADP-ribose 1"-phosphate. Although the sequence identity between the two proteins is remarkably low (9.3%), the 2'-5' RNA ligase and CPDase structures have two HX(T/S)X motifs in their corresponding positions. The HX(T/S)X motifs play important roles in the CPDase activity, and are conserved in both the CPDases and 2'-5' RNA ligases. Therefore, the catalytic mechanism of the 2'-5' RNA ligase may be similar to that of the CPDase. On the other hand, the electrostatic potential of the cavity of the 2'-5' RNA ligase is positive, but that of the CPDase is negative. Furthermore, in the CPDase, two loops with low B-factors cover the cavity. In contrast, in the 2'-5' RNA ligase, the corresponding loops form an open conformation and are flexible. These characteristics may be due to the differences in the substrates, tRNA and ADP-ribose 1",2"-cyclic phosphate.     

Cyclohexanoid protoflavanones from the stem-bark and roots of Ongokea gore

Phytochemical investigation of root and stem-bark of the West African medicinal plant Ongokea gore resulted in the isolation of four novel flavonoids with an unusual cyclohexyl substituent instead of the common aromatic ring B. The structures of the isolated compounds were elucidated by spectroscopic methods, mainly 1D and 2D NMR, and subsequently, the structures were corroborated by chemical conversion to (-)-(S)-sakuranetin. The absolute configurations, and preferred conformations were determined by NOE experiments and CD measurements.     

Flavones and isoflavones from the west African Fabaceae Erythrina vogelii

The CH(2)Cl(2)/MeOH extract of the stem bark of Erythrina vogelii (Fabaceae) from Nigeria has yielded two novel isoflavones, 7,4'-dihydroxy-8-(gamma,gamma-dimethylallyl)-2'zeta-(4'-hydroxyisopropyl)dihydrofurano[1',3':5,6]isoflavone (vogelin H) (1) and 7,4'-dihydroxy-8-[(2'zeta,3'-dihydroxy-3'-methyl)butyl]-2',2'-dimethyl-3',4'-dehydropyrano[1',4':5,6]isoflavone (vogelin I) (2), a novel flavone, 7,4'-dihydroxy-2',2'-dimethyl-3',4'-dehydropyrano[1',4':5,6]flavone (vogelin J) (3), and eight known flavonoids.     

Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis

Antifungal activity guided fractionation of the n-butanol extract from the methanol extract of the leaves of Artocarpus nobilis furnished 2',4',4-trihydroxy-3'-geranylchalcone (1), 2 ',4',4-trihydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (2), 2',4',4-trihydroxy-3'-[2-hydroxy-7-methyl-3-methylene-6-octaenyl]chalcone (3), 2',3,4,4'-tetrahydroxy-3'-geranylchalcone (4), 2',3,4,4'-tetrahydroxy-3'-[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl]chalcone (5). The chalcones 3 and 5 are new natural products whereas 1 and 2 are reported first time from the family Moraceae. All these compounds showed good fungicidal activity against Cladosporium cladosporioides and high radical scavenging activity towards the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical in TLC bio-autography method.     

Alkaloids from Galanthus nivalis

Phytochemical studies on Galanthus nivalis of Bulgarian origin resulted in the isolation of five compounds: 11-O-(3'-hydroxybutanoyl)hamayne, 3,11-O-(3',3'-dihydroxybutanoyl)hamayne, 3-O-(2'-butenoyl)-11-O-(3'-hydroxybutanoyl)hamayne, 3,11,3'-O-(3',3',3'-trihydroxybutanoyl)hamayne, and 2-O-(3'-acetoxybutanoyl)lycorine, together with five known alkaloids: ungeremine, lycorine, tazettine, hamayne, and ismine. Their structures were determined by (1)H and (13)C NMR spectroscopy and two-dimensional (1)H-(1)H and (1)H-(13)C chemical shift correlation experiments.     

长形肉豆蔻Myristica argentea Warb.化学成分研究(英文)

从长形肉豆蔻Myristica argentea乙醇提取物乙酸乙酯部分分离得到12个化合物,经理化和波谱分析分别鉴定为黄樟醚(1)、甲基丁香酚(2)、异甲基丁香酚(3)、3′-羟基异黄樟醚(4)、7-羟基-3′,4′-亚甲二氧基黄烷(5)、1,4-苯二甲酸二甲酯(6)、内消旋-二氢愈创木脂酸(7)、赤式-1-(4-羟基-3-甲氧基苯基)-4-(3,4-亚甲二氧基苯基)-2,3-二甲基丁烷(8)、赤式-1-(4-羟基-3-甲氧基苯基)-2-(2-甲氧基-4-(1(E)-丙烯基)苯氧基)-丙烷-1-醇(9)、nectandrin B(10)、β-谷甾醇(11)和胡萝卜苷(12)。化合物4~6和8~12为首次自该植物中分离得到,化合物4~6为首次从该属植物中分离得到。     

Chemotaxonomic relevance of cardenolides in Urginea fugax

In a chemotaxonomic approach the investigation of a methanolic extract of bulbs of Urginea fugax (MORIS) STEINH. resulted in the detection of several cardenolides. The structure of a novel compound, named fugaxin (1), was established as 12alpha,14beta-dihydroxy-2alpha,3beta-(tetrahydro-3',5'-dihydroxy-4'-methoxy-6'-methyl-2H-pyran-2',4'-diylbisoxy)-card-4,20-dienolide by extensive NMR spectroscopic studies including 2D-NMR techniques (COSY, HSQC, HMQC) and selective 1D experiments (NOE, TOCSY) as well as HR-ESI-MS. The chemotaxonomic relevance of the occurrence of cardenolides in the genus Urginea is discussed.     

A benzoisofuranone derivative and carbazole alkaloids from Murraya koenigii and their antimicrobial activity

A benzoisofuranone derivative, 3xi-(1xi-hydroxyethyl)-7-hydroxy-1-isobenzofuranone, and a dimeric carbazole alkaloid, 3,3'-[oxybis(methylene)]bis(9-methoxy-9H-carbazole), along with six known carbazole alkaloids and three known steroids were isolated from the stem bark of Murraya koenigii. The structures of these compounds were established unambiguously by UV, IR, MS and a series of 1D and 2D NMR analyses. The minimum inhibitory concentrations (MIC) of these compounds were found to be in the range 3.13-100 microg/ml.     

A rationale for the shift in colour towards blue in transgenic carnation flowers expressing the flavonoid 3',5'-hydroxylase gene

Recently marketed genetically modified violet carnations cv. Moondust and Moonshadow (Dianthus caryophyllus) produce a delphinidin type anthocyanin that native carnations cannot produce and this was achieved by heterologous flavonoid 3',5'-hydroxylase gene expression. Since wild type carnations lack a flavonoid 3',5'-hydroxylase gene, they cannot produce delphinidin, and instead accumulate pelargonidin or cyanidin type anthocyanins, such as pelargonidin or cyanidin 3,5-diglucoside-6"-O-4, 6"'-O-1-cyclic-malyl diester. On the other hand, the anthocyanins in the transgenic flowers were revealed to be delphinidin 3,5-diglucoside-6"-O-4, 6"'-O-1-cyclic-malyl diester (main pigment), delphinidin 3,5-diglucoside-6"-malyl ester, and delphinidin 3,5-diglucoside-6",6"'- dimalyl ester. These are delphinidin derivatives analogous to the natural carnation anthocyanins. This observation indicates that carnation anthocyanin biosynthetic enzymes are versatile enough to modify delphinidin. Additionally, the petals contained flavonol and flavone glycosides. Three of them were identified by spectroscopic methods to be kaempferol 3-(6"'-rhamnosyl-2"'-glucosyl-glucoside), kaempferol 3-(6"'-rhamnosyl-2"'-(6-malyl-glucosyl)-glucoside), and apigenin 6-C-glucosyl-7-O-glucoside-6"'-malyl ester. Among these flavonoids, the apigenin derivative exhibited the strongest co-pigment effect. When two equivalents of the apigenin derivative were added to 1 mM of the main pigment (delphinidin 3,5-diglucoside-6"-O-4,6"'-O-1-cyclic-malyl diester) dissolved in pH 5.0 buffer solution, the lambda(max) shifted to a wavelength 28 nm longer. The vacuolar pH of the Moonshadow flower was estimated to be around 5.5 by measuring the pH of petal. We conclude that the following reasons account for the bluish hue of the transgenic carnation flowers: (1). accumulation of the delphinidin type anthocyanins as a result of flavonoid 3',5'-hydroxylase gene expression, (2). the presence of the flavone derivative strong co-pigment, and (3). an estimated relatively high vacuolar pH of 5.5.     

Constituents of the stems of Macrococculus pomiferus and their inhibitory activities against cyclooxygenases-1 and -2

As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1 and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the basis of their CD spectra. All isolates obtained in the present study were evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'-methoxyyatein (3) showed weak activity against COX-2, while all other compounds isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was also traced to the presence of several common fatty acids by LC-MS.     

Prenylated flavonoids from Moghania philippinensis

Five prenylated flavonoids, 8-(1,1-dimethylallyl)genistein (1), 5,7,3',4'-tetrahydroxy-2',5'-di(3-methylbut-2-enyl)isoflavone (2), 5,7,3'-trihydroxy-2'-(3-methylbut-2-enyl)-4',5'-(3,3-dimethylpyrano)isoflavone (3), (2R)-5,2',4'-trihydroxy-8,5'-di(3-methylbut-2-enyl)-6,7-(3,3-dimethylpyrano)flavanone (4a) and (2S)-5, 2', 4'-trihydroxy-8,5'-di(3-methylbut-2-enyl)-6,7-(3,3-dimethylpyrano)flavanone (4b), were isolated from the roots of Moghania philippinensis. The structures of these compounds were determined on the basis of spectroscopic and chemical means.     

Antioxidant aryl-prenylcoumarin, flavan-3-ols and flavonoids from Eysenhardtia subcoriacea

Antioxidant activity (AOA) assay-guided chemical analysis, using a rat pancreas homogenate model, of aerial parts from Eysenhardtia subcoriacea, led to isolation of the new compound subcoriacin (3-(2'-hydroxy-4',5'-methylendioxyphenyl)-6-(3'-hydroxymethyl-4'-hydroxybut-2'-enyl)-7-hydroxycoumarin) together with the known substances: (+)-catechin, (-)-epicatechin, (+)-afzelechin, eriodictyol, (+)-catechin 3-O-beta-D-galactopyranoside and quercetin 3-O-beta-D-galactopyranoside as bioactive constituents. The structure of the compound was determined from 1D and 2D NMR spectroscopic analyses. Additional known constituents were characterized. The bioactive compounds showed also moderate to strong radical scavenging properties against diphenylpicrylhydrazyl radical (DPPH). In addition, subcoriacin, (+)-catechin, (-)-epicatechin and (+)-afzelechin improved the reduced glutathione levels in rat pancreatic homogenate.     

Antimicrobial constituents from the stem bark of Feronia limonia.

The stem bark of Feronia limonia (Fam. Rutaceae) yielded (-)-(2S)-5,3'-dihydroxy-4'-methoxy-6",6"-dimethylchromeno-(7,8,2",3")-flavanone along with several known compounds including an alkaloid, five coumarins, a flavanone, a lignan, three sterols and a triterpene. The structures of these compounds were determined by spectroscopic methods, mainly 1D and 2D NMR. The antimicrobial screening of compounds by a microdilution technique resulted in MICs in the range 25-100 microg/ml. Other biological activities of the known compounds are also discussed.     

Prenylated chalcones, flavone and other constituents of the twigs of Dorstenia angusticornis and Dorstenia barteri var. subtriangularis

The twigs of Dorstenia angusticornis and Dorstenia barteri var. subtriangularis yielded 16 compounds. Two novel diprenylated chalcones: 3,5'-di-(2-hydroxy-3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone, 3, 4-(2,2-dimethylpyrano)-3'-(2-hydroxy-3-methylbut-3-enyl)-2',4'-dihydroxychalcone and the known stipulin were isolated from both species. 3-(2-Hydroxy-3-methylbut-3-enyl)-5'-(3,3-dimethylallyl)-4,2',4'-trihydroxychalcone and the known compounds: 4-hydroxylonchocarpin, kanzonol B, bartericins A, B, C and 3'-(2-hydroxy -3-methylbut-3-enyl)-4,2',4'-trihydroxychalcone were isolated from D. barteri while the known compounds: gancaonin Q, paratocarpins C, F, and lupeol were obtained from Dorstenia angusticornis. beta-Sitosterol and its beta-d-glucopyranoside were isolated from both species. Structures of these secondary metabolites were established using spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HMQC and HMBC.     

Flavones from Andrographis viscosula

Two new 2'-oxygenated flavones, 5,7,2'-trimethoxyflavone (1). and 5,7,2',4',6'-pentamethoxyflavone (2). were isolated from the whole plant of Andrographis viscosula along with three known flavones, echioidinin (3). 5,2',6'-trihydroxy-7-methoxyflavone (4). and echioidin (5). The structures of these compounds were elucidated on the basis of 1D and 2D NMR spectral studies.