Anti-plasmin inhibitor. V. Structures of novel dimeric eckols isolated from the brown alga Ecklonia kurome OKAMURA

6,6'-Bieckol (1), 2-O-(2,4,6-trihydroxyphenyl)-6,6'-bieckol (4), and 8,8'-bieckol (2), bispolyphenols with a dibenzo-1,4-dioxin skeleton, have been isolated as potent anti-plasmin inhibitors from the brown alga Ecklonia kurome OKAMURA. Their structures have been determined to be dimers of eckol linked at the C-6 or C-8 positions, through an aryl-aryl bond on the basis of spectral data. Their inhibitory actions on anti-plasmins (alpha 2-macroglobulin and alpha 2-plasmin inhibitor) and some proteases have been examined.     

Anti-plasmin inhibitor. VI. Structure of phlorofucofuroeckol A, a novel phlorotannin with both dibenzo-1,4-dioxin and dibenzofuran elements, from Ecklonia kurome Okamura

Phlorofucofuroeckol A (1), a novel phlorotannin with both dibenzo-1,4-dioxin and dibenzofuran elements, has been isolated from the brown alga Ecklonia kurome OKAMURA as a potent anti-plasmin inhibitor. Its structure has been elucidated to be 1,11-di(3,5-dihydroxyphenoxy)- benzofuro[3,2-a]dibenzo[b,e][1,4]dioxin-2,4,8,10,14-pentaol on the basis of the spectral data, in particular, by means of negative nuclear Overhauser effect (NOE) and long-range carbon-proton couplings (2JCH and 3JCH). Phlorofucofuroeckol A inhibited the action of alpha 2-macroglobulin (IC50 = 1.0 micrograms/ml) and alpha 2-plasmin inhibitor (IC50 = 0.3 micrograms/ml), the main plasmin inhibitors in plasma.     

New chromane derivatives isolated from the brown alga, Sargassum micracanthum

Two new chromane type meroterpenoids were isolated from the methanolic extract of the brown alga, Sargassum micracanthum. Their structures were elucidated based on spectroscopic analysis and chemical conversion. The absolute stereochemistry of the methyl group at C-8' in 1 and related compounds were determined by modified Mosher's method.     

New plastoquinones isolated from the brown alga, Sargassum micracanthum

Four new plastoquinones were isolated from the methanolic extract of the brown alga, Sargassum micracanthum. Their structures were elucidated based on spectroscopic analysis and chemical conversions from 2-geranylgeranyl-6-methyl-1,4-benzohydroquinone. These plastoquinones exhibited significant antioxidant activities such as an inhibitory effect on lipid peroxidation and a radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH). Some of the new plastoquiones showed cytotoxic activity against cancer cell line.     

Bifurcarenone,an inhibitor of mitotic cell division from the brown alga bifurcaria galapagensis

A C₂₇ hydroquinone, bifurcarenone, apparently produced $\text{via}$ mixed biosynthesis, has been isolated from the brown seaweed $\text{Bifurcaria galapagensis}$ (Cystoseiraceae). The structure of bifurcarenone was determined by chemical and spectral methods, and this compound was found to exhibit antibacterial properties, as well as to inhibit cell cleavage of the fertilized egg from the urchin $\text{Strongylocentrotus purpuratus}$.     

Development of potent and selective plasmin and plasma kallikrein inhibitors and studies on the structure-activity relationship

Based on structure-activity relationship studies, we designed and synthesized plasmin (PL) and plasma kallikrein (PK) inhibitors. Trans-(4-aminomethylcyclohexanecarbonyl)-Tyr(O-Pic)-octylamide inhibited PL, PK, urokinase (UK) and thrombin (TH) with IC50 values of 0.53, 30, 5.3 and > 400 microm, respectively. Trans-(4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-Pyrim)-4-carboxyanilide inhibited PL, PK, UK and TH with IC50 values of 36, 0.56, 440 and > 1,000 microM, respectively.     

Antioxidant, antimicrobial and tyrosinase inhibitory activities of xanthones isolated from Artocarpus obtusus F.M. Jarrett

One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 μg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.     

Cytotoxic and insecticidal activities of derivatives of harmine, a natural insecticidal component isolated from Peganum harmala

In a continuing effort to develop novel β-carbolines endowed with better insecticidal activity, a simple high-yielding method for the synthesis of harmine compounds starting from L-tryptophan has been developed and a series of 1,3-substituted β-carboline derivatives have been synthesized and evaluated for their cytotoxicity against insect cultured Sf9 cell line in vitro and insecticidal activities against 4th instar larvae of mosquitos, Culex pipiens quinquefasciatus and mustard aphid, Lipaphis erysimi. The results demonstrated that 1-phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (compound 2) and methyl 1-phenyl-β-carboline-3-carboxylate (compound 13) represented the best potential compounds, with Sf9 cells inhibition rates of 71.55% and 60.21% after 24 h treatment at concentrations of 50-200 mg/L, respectively. Both compounds 2 and 13 also showed strong insecticidal activity towards 4th instar larvae of mosquitos with LC(50) values of 20.82 mg/L and 23.98 mg/L, and their LC(90) values were 88.29 mg/L and 295.13 mg/L, respectively. Furthermore, the LC(50) values of compounds 2 and 13 against mustard aphids were 53.16 mg/L and 68.05 mg/L, and their LC(90) values were 240.10 mg/L and 418.63 mg/L after 48 h treatment. The in vitro cytotoxicity of these compounds was consistent with the insecticidal activity in vivo. The results indicated that the 1- and 3-positions of the β-carboline ring deserve further investigation to develop biorational insecticides based on the natural compound harmine as a lead compound.     

Structure and chemistry of 1-silafluorenyl dianion, its derivatives, and an organosilicon diradical dianion.

1-Silafluorene dianion was synthesized by potassium reduction of 1,1-dichloro-1-silafluorene in refluxing THF. The X-ray structure of 1,1-dipotassio-1-silafluorene (3b) shows C-C bond length equalization in the five-membered silole ring and C-C bond length alternation in the six-membered benzene rings, indicating aromatic delocalization of electrons in the silole ring. The downfield (29)Si chemical shift at 29.0 ppm and theoretical calculations also support electron delocalization in the silole ring of 3b. Dianion salt 3b underwent nucleophilic reactions with Me(3)SiCl and EtBr to form the corresponding disubstituted products. Benzaldehyde underwent reductive coupling in the presence of 3b. Slow oxidation of 3b yielded 1,1'-dipotassio-1,1'-bis(silafluorene) (16). The X-ray structure and (29)Si chemical shift (-38.0 ppm) of 16 indicate localized negative charges at the silicon atoms and no aromatic character. Heating a DME/hexane solution of 3b in the presence of 18-crown-6 led to a novel diradical dianion salt.     

Two new triterpenes from the Rhizome of Dryopteris crassirhizoma, and inhibitory activities of its constituents on human immunodeficiency virus-1 protease

Two new hopane type triterpenes, named dryopteric acids A (1) and B (2), were isolated from the Rhizome of Dryopteris crassirhizoma (Aspiadaceae) together with sixteen known compounds (3-18). Of isolated compounds, ursolic acid (15), and dryopteric acid A (1) and B (2) showed potent inhibitory activities against HIV-1 protease with IC50 values of 8.9-44.5 microM. In addition, acetylated compounds 1 and 2 appreciably increased inhibitory activities with their IC50 values of 1.7 and 10.8 microM, respectively.     

Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B

The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.     

Structure and antitumor activity of the less-branched derivatives of an alkali-soluble glucan isolated from Omphalia lapidescens. (Studies on fungal polysaccharide. XXXVIII).

The structure and antitumor activity of Smith-type degradation products (OL-2-I, OL-2-II and OL-2-III) of an alkali-soluble glucan, OL-2, isolated from a crude fungal drug "Leiwan" (Omphalia lapidescens) were investigated. Methylation analysis suggested that OL-2-I was a (1----3)-beta-D-glucan with approximately one branch at every three main chain glucosyl units at each C-6 position; OL-2-II was a (1----3)-beta-D-glucan with approximately one branch at twenty four main chain glucosyl units at each C-6 position (number of all main chain glucosyl units is on average). OL-2-I, OL-2-II and OL-2-III which were Smith-type degradation products of OL-2, showed potent antitumor activity against the solid form of sarcoma 180 in ICR mice. These results indicated that the degree of beta-linked branching at position 6 was remarkably related to the antitumor activity.     

Isolation,characterization, and xanthine oxidase inhibitory activities of flavonoids from the leaves of Perilla frutescens

Abstract

Phytochemical investigation of the water extract from the leaves of Perilla frutescens (Lamiaceae) led to the isolation of a new flavanone, a new chalcone, and a new aurone, namely, (2S)-5,7-dimethoxy-8,4'-dihydroxyflavanone (1), 2',4'-dimethoxy-4,5',6'-trihydroxychalcone (2), and (Z)-4,6-dimethoxy-7,4'-dihydroxyaurone (3), respectively. The structures were unambiguously elucidated on the basis of spectroscopic data. And the absolute configuration of 1 was determined by analysis of electronic circular dichroism spectrum. The isolated compounds were evaluated for their inhibitory effects on xanthine oxidase in vitro. Among them, 2 showed more potent activity than the positive control allopurinol, a well-known XO inhibitor clinically used for treatment of gout. Lineweaver-Burk transformation of the inhibition kinetics data demonstrated that it was a mixed-type inhibitor.

     

Structure activity relationship of bergenin,p-hydroxybenzoyl bergenin, 11-O-galloylbergenin as potent antioxidant and urease inhibitor isolated from Bergenia ligulata

Ethanol extract of the aerial parts of Bergenia ligulata was subjected to solvent–solvent separation followed by various chromatographic techniques that lead to isolation of bergenine (1), p-hydroxybenzoyl bergenin (2), 11-O-galloylbergenin (3) and methyl gallate (4) as major constituents. Ethyl acetate fraction showed a dose-dependent urease inhibitory pattern with IC₅₀ value of 54μg/mL. Structures of compounds 1 and 3 were established by XRD and 2, 4 by NMR. All these compounds were subjected to DPPH scavenging activity, reducing power assay and urease inhibitory activity. The EC₅₀ 7.45 ± 0.2 μg/mL and 5.39 ± 0.28 μg/mL values in terms of antioxidant and reducing power, respectively, were less for 3. Compounds 1–3 showed moderate to significant urease inhibitory potential with IC₅₀ 57.1 ± 0.7, IC₅₀ 48.4 ± 0.3 and 38.6 ± 1.5. Antioxidant activities and urease inhibitory potential were investigated and compound 3 was found to be the most active.     

Total syntheses of makaluvamines A, B, C, D and E, cytotoxic pyrroloiminoquinone alkaloids isolated from marine sponge bearing inhibitory activities against topoisomerase II

Syntheses of makaluvamines A, B, C, D and E (1 – 5), new members of tetrahydropyrroloiminoquinone alkaloids, have been successfully carried out. Particularly, olefin introduction for makaluvamines B and E could be achieved by Pd - mediated and E₂ type methodologies.     

Studies on angiotensin converting enzyme inhibitors. VI. Synthesis and angiotensin converting enzyme inhibitory activities of the dicarboxylic acid derivative of imidapril and its diastereoisomers.

All possible diastereoisomers of the dicarboxylic acid (10a), the biologically active form of imidapril (1), were synthesized, and their inhibitory activity against angiotensin converting enzyme (ACE) was examined. The in vitro ACE inhibitory activity of these compounds greatly depended on the configurations of the three asymmetric carbons in each molecule. The (S,S,S) isomer (10a) showed much more potent activity than the others.     

壳聚糖及其衍生物溶液浇铸膜的结构研究

用偏光显微镜小角光散射、扫描电镜和大角度X-光衍射技术研究了壳聚糖及其衍生物丁酸壳聚糖、苯甲酸壳聚糖的溶液浇铸膜的结构。用低于液晶临界浓度的稀溶液能制备具有液晶织构的膜。观察到指纹状织构、正光性滴状织构和负光性滴状织构．后两种滴状织构内分子自组织构型分别为辐射型和双极型。