Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii

Assay-guided fractionation of the ethanol extract of Tovomita krukovii resulted in the identification of four new xanthones (1 - 4) and ten known compounds (5 - 14). The structures of compounds 1 - 14 were determined by spectral data to be 3,5-dihydroxy-4-methoxyxanthone (1), 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (2), 1,3,5-trihydroxy-8-isoprenylxanthone (3), 1,5,7-trihydroxy-8-isoprenylxanthone (4), 1,3,7-trihydroxy-2-isoprenylxanthone (5), 1,5-dihydroxyxanthone (6), 1,6-dihydroxy-5-methoxyxanthone (7), 1,3,5-trihydroxyxanthone (8), 1,3,6-trihydroxy-5-methoxyxanthone (9), 1,6-dihydroxy-3,5-dimethoxyxanthone (10), 1,3,7-trihydroxyxanthone (11), 3-geranyl-2,4,6-trihydroxybenzophenone (12), betulinic acid (13), and 3,4-dihydroxybenzoic acid (14). Compounds 2, 3, 12 and 13 showed inhibitory effects against Candida albicans secreted aspartic proteases (SAP) with IC50 values of 15 microg/ml, 25 microg/ml, 40 microg/ml, and 6.5 microg/ml, respectively, while the other compounds were inactive. In addition, compound 12 showed activity against C. albicans, C. neoformans, S. aureus and methicillin resistant S. aureus (MRS).     

A new auronol from Cudrania cochinchinensis

A new auronol, cudrauronol (1), was isolated from the roots of Cudrania cochinchinensis along with 10 known compounds, 1,3,5-trihydroxy-4-prenylxanthone (2), 1,3,7-trihydroxy-4-prenylxanthone (3), 3,4',5,7-tetrahydroxydihydroflavonol (4), kaempferol (5), 3,6-dihydroxy-1,5-dimethoxyxanthone (6), 2',4',5,7-tetrahydroxyflavanolol (7), 3,7-dihydroxy-1-methoxyxanthone (8), 1,3,5-trihydroxyxanthone (9), cudraflavone B (10), and 2'-oxyresveratrol (11). Compounds 1-8 were evaluated for anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 2-5 were more active than aminoguanidine, with IC(50) values of 8.8, 23.2, 27.1, and 11.9?μM, respectively.     

Xanthones from the roots of Polygala caudata and their antioxidation and vasodilatation activities in vitro

Three new xanthones, 2-hydroxy-1,6,7-trimethoxyxanthone (1), 1,4-dimethoxy-2,3-methylenedioxyxanthone (2), and 7-hydroxy-1,2-dimethoxyxanthone (3), together with five known compounds, 2,7-dihydroxy-1-methoxyxanthone (4), 1-methoxy-2,3-methylenedioxyxanthone (5), 7-hydroxy-1-methoxyxanthone (6), euxanthone (1,7-dihydroxyxanthone) (7), and gentitein (1,3,7-trihydroxyxanthone) (8), were isolated from the roots of Polygala caudata. Their structures were established on the basis of spectral evidence. In the antioxidation activity screening in vitro with luminol chemiluminescence methods, compounds 1 - 5 and 7 and 8 showed H2O2 scavenger activity, with a scavenging effect of 58.4 - 94.5% at 10 microg/mL, and 26.0 - 84.7% at 2 microg/mL. Compounds 4 and 8 also exhibited scavenging effects on the reactive oxygen free radicals produced by macrophage respiratory bursts, with a scavenging effect of 71.7% and 63.4% at 10 microg/mL, 41.2% and 47.8% at 2 microg/mL, respectively. In the vasodilatation assay, compounds 4 - 7 exhibited relaxing activity on the contractions evoked by KCl in Wistar rat thoracic aorta rings in a dose-dependent manner.     

Lupane triterpenoids and a diarylheptanoid from Clematoclethra actinidioides

Three new compounds, actinidione ( 1), 3 beta,29-dihydroxylup-20(30)-en-28-al ( 2) and 3 beta- O- trans-caffeoyl-29-hydroxybetulin ( 3), along with twenty known compounds ( 4 - 23), were isolated from the leaves and twigs of Clematoclethra actinidioides Maxim. Their structures were determined by analysis of spectral data or comparison with authentic samples. Compounds 1, 2 and 3 exhibited cytotoxicity against Lu-06, N-04 and Bre-04 cell lines with GI (50) values of 15.02 - 41.64 microg/mL.     

New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase

Ten compounds, harpagoside (1), 8- p-coumaroylharpagide (2), 8-feruloylharpagide (3), 8-cinnamoylmyoporoside (4), pagoside (5), acteoside (6), isoacteoside (7), 6'- O-acetylacteoside (8), cinnamic acid (9) and caffeic acid (10) were isolated from the storage roots of Harpagophytum procumbens, Pedaliaceae. Compounds 1, 2, 6, 7 and 9 are known for H. procumbens; 3 and 10 were isolated the first time from H. procumbens; compounds 4, 5 and 8 are new natural products. Their structures were elucidated using spectroscopic data (NMR, with NOE, COSY and HMBC experiments, UV, [alpha]). The inhibitory activity of aqueous extracts of the roots of H. procumbens and H. zeyheri as well as the main compounds isolated from H. procumbens was tested on human neutrophile elastase. Although inhibition was comparatively weak a dose-dependence was observed. An IC (50) of 542 microg/mL was determined for the aqueous extract of H. procumbens, but 1012 microg/mL for that of H. zeyheri. 6'- O-Acetylacteoside (8), that is not present in H. zeyheri, inhibited the enzyme with an IC (50) of 47 microg/mL (70 microM), compound 7 with 179 microg/mL (286 microM), 2 with 179 microg/mL (331 microM), 5 with 154 microg/mL (260 microM) and 10, which was also used as reference compound, with an IC (50) of 86 microg/mL (475 microM). The IC (50) values of acteoside, harpagoside, cinnamic acid and stachyose were higher than 300 microg/mL and thus not further determined.     

Xanthones from the roots of Cudrania fruticosa Wight

Chemical investigation on the roots of Cudrania fruticosa resulted in the isolation of two new xanthones, 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (1) and 3,6,7-trihydroxy-1-methoxyxanthone (2), together with three known ones, 1,3,5-trihydroxy-4-(3-hydroxy-3-methylbutyl)xanthone (3), 1,3-dihydroxy-6,7-dimethoxyxanthone (4) and 3,5,6-trihydroxy-1-methoxyxanthone (5), respectively. Their structures were elucidated on the basis of spectral and chemical techniques.     

Xanthones from the roots of Cudrania fruticosa Wight

Chemical investigation on the roots of Cudrania fruticosa resulted in the isolation of two new xanthones, 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (1) and 3,6,7-trihydroxy-1-methoxyxanthone (2), together with three known ones, 1,3,5-trihydroxy-4-(3-hydroxy-3-methylbutyl)xanthone (3), 1,3-dihydroxy-6,7-dimethoxyxanthone (4) and 3,5,6-trihydroxy-1-methoxyxanthone (5), respectively. Their structures were elucidated on the basis of spectral and chemical techniques.     

Anthocleistenolide, a new rearranged nor-secoiridoid derivative from the stem back of Anthocleista vogelii

A new rearranged nor-secoiridoid, anthocleistenolide ( 1), along with the known 1-hydroxy-3,7-dimethoxyxanthone ( 2), 1-hydroxy-3,7,8-trimethoxyxanthone ( 3), 7 alpha-hydroxysitosterol ( 4) and sitosterol 3- O-beta- D-glucopyranoside ( 5), were isolated from the stem back of Anthocleista vogelii. Their structures were elucidated on the basis of spectral studies and comparison with published data. Compounds 1 - 3 and 5 were evaluated for their antibacterial and antifungal activities. Relatively low anti-staphylococcal (MIC = 200 microg/mL against Staphylococcus aureus) and anti-enterococcal (MIC = 100 microg/mL against Enterococcus faecalis) activities were observed for 1, while compounds 2 and 3 were active against Candida parapsilosis (MIC = 200 microg/mL for 2 and 25 microg/mL for 3). Compound 5 was inactive against all the bacterial and fungal species used.     

长毛籽远志根的化学成分研究

为长毛籽远志Polygala wattersii的质量控制和进一步的开发提供科学依据,我们对它的根进行了系统的化学成分研究。利用砖胶、SephadexLH-20、制备薄层色谱及半制备液相等多种色谱分离技术进行分离和纯化,应用El—MS、ESI—MS、1HNMR及13CNMR等现代波谱技术并与文献相对照等方法鉴定化合物的结构。共从长毛籽远志根中分离鉴定了23个化合物,包括11个[口山]酮类：1,3-二羟基[口山]酮（1）,1-羟基-3-甲氧基[口山]酮（2）,1,3-羟基-2-甲氧基[口山]酮（3）,1,3,7-三羟基-2-甲氧基[口山]酮（4）,1,3,6-三羟基-2,7-二甲氧基[口山]酮（5）,1,6,7-三羟基-2,3-二甲氧基[口山]酮（6）,1,7-二羟基-2,3-亚甲二氧基[口山]酮（7）,1,7-二甲氧基[口山]酮（8）,1,2,3-三甲氧基[口山]酮（9）,1-甲氧基-2,3-亚甲二氧基[口山]酮（10）,6-羟基-1-甲氧基-2,3-亚甲二氧基[口山]酮（11）;9个糖酯类：3＇-O-阿魏酰基-6-O-乙酰蔗糖（12）,arillatose B（13）,sibficoseA5（14）,sibricoseA6（1S）,3＇,6-二-O-芥子酰基蔗糖（16）,tenufolisideA（17）,3＇-O-3,4,5-三甲氧基肉桂酰基-6—O-对甲氧基苯甲酰基蔗糖（18）,glomeratoseA（19）,1-O--对香甄酰基葡萄糖（20）;两个三萜皂苷类：bayogenin-3—O-glucoside（21）和tenufolin（22）及1个苯丙素类：芥了酸（23）。其中,化合物2和12为首次从远志属中分离得到,除化合物16外其它所有化合物均为首次从该种植物中分离得到。     

Synthesis and antitumor activities of novel pyrimidine derivatives of 2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid and 4,5-didehydro-5,6- dideoxy-L-ascorbic acid

The new pyrimidine derivatives of 2,3-O, O-dibenzyl-6-deoxy-L-ascorbic acid (8-10) were synthesized by condensation of uracil and its 5-fluoro- and 5-trifluoromethyl-substituted derivatives with 4-(5,6-epoxypropyl)-2, 3-O,O-dibenzyl-L-ascorbic acid (7), while pyrimidine derivatives of 4,5-didehydro-5,6-dideoxy-L-ascorbic acid (14-17) with free C-2' and C-3' hydroxy groups in the lactone ring were obtained by debenzylation of 11-13 with boron trichloride. Z-Configuration of the C4'=C5' double bond and position of the benzyl group in the lactone ring of 14 were deduced from their (1)H and (13)C NMR spectra and connectivities in COSY, ROESY, and HMBC spectra. The exact stereostructure of 13 was confirmed by its X-ray crystal structure analysis. Of all the compounds in the series, compound 16 containing a 5-fluoro-substituted uracil ring showed the most significant antitumor activities against murine leukemia L1210/0 (IC(50) = 1.4 microg/mL), murine mammary carcinoma FM3A/0 (IC(50) = 0.78 microg/mL), and, to a lesser extent, human T-lymphocyte cells Molt4/C8 (IC(50) = 31.8 microg/mL) and CEM/0 cell lines (IC(50) = 20.9 microg/mL).     

A new antioxidant isobenzofuranone derivative from the algicolous marine fungus Epicoccum sp

The fungus Epicoccum sp., was isolated from the marine brown alga Fucus vesiculosus. After cultivation the fungus was investigated for its secondary metabolite content, and found to contain the new natural product 4,5,6-trihydroxy-7-methylphthalide (1, epicoccone), together with 5-(acetoxymethyl)-furan-2-carboxylic acid (2), furan-2-carboxylic acid (3), 5-(hydroxymethyl)-furan-2-carboxylic acid (4), (-)-(3 R,4 S)-4-hydroxymellein (5), and (-)-(3 R)-5-hydroxymellein (6). The structures of all compounds were determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV, optical rotation and IR). Each isolate was tested for its antioxidative properties. Compound 1 was found to be potently active, showing 95 % DPPH radical scavenging effects at 25 microg/mL. Compound 1 also inhibited the peroxidation of linolenic acid in the TBARS assay (62 % inhibition at 37 microg/mL).     

Water-soluble, core-modified porphyrins as novel, longer-wavelength-absorbing sensitizers for photodynamic therapy

Water-soluble, core-modified 5,10,15, 20-tetrakis(4-sulfonatophenyl)-21,23-dithiaporphyrin (1) and 5,10,15, 20-tetrakis(4-sulfonatophenyl)-21,23-diselenaporphyrin (2) were prepared as the tetrasodium salts by the sulfonation of 5,10,15, 20-tetraphenyl-21,23-dithiaporphyrin (3) and -21, 23-diselenaporphyrin (4), respectively, with sulfuric acid. Compounds 3 and 4 were prepared by the condensation of pyrrole with either 2,5-bis(phenylhydroxymethyl)thiophene (5) or 2, 5-bis(phenylhydroxymethyl)selenophene (6) in propionic acid. The addition of benzaldehyde to 2,5-dilithiothiophene or 2, 5-dilithioselenophene gives 5 or 6, respectively, as a nearly equimolar mixture of meso- and d,l-diastereomers. Careful crystallization of 5 gives a single diastereomer by removing the crystalline product from the equilibrating mixture of diastereomers in solution. Photodynamic therapy (PDT) with 1 has an LD(50) of less than 25 microg/mL against Colo-26 cells in culture and exhibits a lethal dose for 90% or more at concentrations greater than 50 microg/mL. In contrast, PDT with 5,10,15, 20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS(4)) requires concentrations of greater than 100 microg/mL to achieve LD(50). Neither 1 nor TPPS(4) shows significant photoactivity against the murine T-cell line, MOLT-4, above the dark toxicity. Sensitizer 1 shows no toxicity or side effects in BALB/c mice observed for 30 days following a single intravenous injection of 10 mg (9.1 micromol)/kg. Distribution studies show that sensitizer 1 accumulates in the tumors of BALB/c mice bearing Colo-26 or EMT-6 tumors with sensitizer concentration roughly doubling as the dosage of 1 increased from 5 to 10 mg/kg. In vivo studies show that PDT with sensitizer 1 at both 3.25 and 10 mg/kg with 135 J cm(-2) of 694-nm light is effective against Colo-26 tumors in BALB/c mice.     

Xanthone glycosides from Swertia franchetiana

A new xanthone glycoside (1) has been isolated from Swertia franchetiana together with five known xanthone glycosides. Their structures were elucidated as 7-O-[beta-D-xylopyranosyl-(1-->2)-beta-D-xylopyranosyl]-1,7,8-trihydroxy-3-methoxyxanthone (1), 7-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl]-1,7,8-trihydroxy-3-methoxyxanthone (2), 8-O-beta-D-glucopyranosyl-1,3,5,8-tetrahydroxyxanthone (3), 1-O-beta-D-glucopyranosyl-1-hydroxy-3,7,8-trimethoxyxanthone (4), 1-O-[beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranosyl]-1-hydroxy-2,3,5-trimethoxyxanthone (5) and 1-O-[beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranosyl]-1-hydroxy-3,5-dimethoxyxanthone (6) on the basis of spectroscopic evidence.     

Coumarins and carbazoles from Clausena excavata exhibited antimycobacterial and antifungal activities

Four known coumarins, dentatin (1), nor-dentatin (2), clausenidin (3) and xanthoxyletin (5), and six known carbazole derivatives, 3-formylcarbazole (6), mukonal (7), 3-methoxycarbonylcarbazole (8), murrayanine (9), 2-hydroxy-3-formyl-7-methoxycarbazole (10) and clauszoline J (11) were isolated from Clausena excavata. Compounds 1 and 6 were first isolated from the crude chloroform extract of the rhizomes. Compounds 1, 2, 3, 6, 7, 8, 10 and 11 showed antimycobacterial activity at a minimum inhibitory concentration (MIC) of 50, 100, 200, 100, 200, 50, 100 and 100 microg/mL, respectively. O-Methylated clausenidin ( 4), prepared from 3, exhibited antimycobacterial activity at MIC 50 microg/mL. Compounds 6, 7, 8 and 10 showed antifungal activity with IC 50 values of 13.6, 29.3, 9.5 and 2.8 microg/mL, respectively. All compounds demonstrated no cytotoxicity against KB and BC-1 cell lines.     

Cytotoxic ent-kaurane diterpenoids from Isodon eriocalyx var. laxiflora

Three new ent-kaurane diterpenoids laxiflorin E (1), laxiflorin H (6) and laxiflorin I (8) were isolated from the leaves of Isodon eriocalyx var. laxiflora, along with nine known diterpenoids, eriocalyxin A (2), laxiflorin C (3), laxiflorin D (4), laxiflorin A (5), maoecrystal S (7), maoecrystal Q (9), eriocalyxin B (10), maoecrystal C (11) and enmelol (12). The structures of the new compounds were determined by spectroscopic methods. Compounds 1-5 are 6,7-seco-ent-kaurane-7,20-olide diterpenoids, and 6-12 belong to 7,20-epoxy-ent-kauranoids. The spectral data of enmelol (12) are reported here for the first time. Ten of these compounds were tested for their cytotoxicity toward K562 and T24 human tumor cells. Compounds 1, 3 and 10 showed significant inhibitory effects on K562 cells with IC50 values 0.077, 0.569 and 0.373 microg/mL, and compounds 1 and 10 also demonstrated significant inhibitory activities toward T24 cells with IC50 values 0.709 and 0.087 microg/mL. Compounds 8 and 11 also displayed inhibitory effect on both two kinds of cells with IC 50 value less than 6.5 microg/mL.     

Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth

1. The present study was conducted to evaluate the cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents on hepatoma and leukaemia cells in vitro. 2. Four human liver cancer cell lines, namely HepG2, Hep3B, SK-Hep1 and PLC/PRF/5, and four leukaemia cell lines, namely K562, U937, P3H1 and Raji, were used in the present study. 3. Of the two crude drugs, C. chinensis exhibited the strongest activity against SK-Hep1 (IC50 = 7 microg/mL) and Raji (IC50 = 4 microg/mL) cell lines. The IC50 values for C. chinensis on HepG2, Hep3B and PLC/PRF/5 cell lines were 20, 55 and 35 microg/mL, respectively. The IC50 values for C. chinensis on K562, U937 and P3H1 cell lines were 29, 29 and 31 microg/mL, respectively. 4. With the exception of HepG2 and Hep3B, the E. sagittatum extract inhibited the proliferation of all cell lines (SK-Hep1, PLC/PRF/5, K562, U937, P3H1 and Raji), with IC50 values of 15, 57, 74, 221, 40 and 80 microg/mL, respectively. 5. Interestingly, the two major compounds of C. chinensis, berberine and coptisine, showed a strong inhibition on the proliferation of both hepatoma and leukaemia cell lines, with IC50 values varying from 1.4 to 15.2 microg/mL and from 0.6 to 14.1 microg/mL, respectively. However, icariin (the major compound of E. sagittatum) showed no inhibition of either the hepatoma or leukaemia cell lines. 6. The results of the present study suggest that the C. chinensis extract and its major constituents berberine and coptisine possess active antihepatoma and antileukaemia activities.     

Sesquiterpenes and other constituents from the aerial parts of Inula japonica

Three new sesquiterpenes, 1beta-hydroxy-8beta-acetoxycostic acid methyl ester, 1beta-hydroxy-8beta-acetoxyisocostic acid methyl ester and 1beta-hydroxy-4alpha,11alpha-eudesma-5-en-12,8beta-olide, along with fourteen known compounds were isolated from the aerial parts of Inula japonica. The structures of these new compounds were elucidated by spectroscopic methods (IR, EIMS, HRMS, 1D and 2D NMR). 1,6alpha-dihydroxy-4alphaH-1,10-secoeudesma-5(10),11(13)-dien-12,8beta-olide exhibited appreciable cytotoxic activity against cultured SMMC-7721 (human hepatoma cell) and HO-8910 (human ovarian carcinoma cell) with IC 50 values of 52.22 and 21.32 microg/mL, while 5alphaH-eudesma-4(15),11(13)-dien-12,8beta-olide showed remarkable cytotoxic activity against cultured SMMC-7721 and HO-8910 with IC 50 values of 6.21 and 5.28 microg/mL, respectively.     

Antifungal metabolite with a new carbon skeleton from Keissleriella sp. YS4108, a marine filamentous fungus

In addition to four known metabolites (4-acetyl-6,8-dihydroxy-5-methylisocoumarin, 6,8-dihydroxy-3-methylisocoumarin, 6,8-dihydroxy-3,5,7-trimethylisocoumarin and 3,3'-oxy-(5-methyl)-phenol), bioassay-guided fractionation of the culture of Keissleriella sp., a marine filamentous fungus (strain number: YS 4108), afforded an antifungal metabolite with a new carbon skeleton whose structure was elucidated spectrometrically as 3,6,8-trihydroxy-3-[3,5-dimethyl-2-oxo-3(E)-heptenyl]-2,3-dihydronaphthalen-1(4H)-one. In vitro antifungal assays of all isolates revealed that the new metabolite and 3,3'-oxybis[5-methylphenol] were inhibitory to the growth of the human pathogenic fungi Candida albicans, Tricophyton rubrum and Aspergillus niger with MICs of the former being 40, 20 and 80 microg/ml, and those of the latter 10, 30 and 50 microg/ml, respectively.