Structure–anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives

We synthesized a series of macrocyclic bis(bibenzyl) derivatives, including riccardin-, isoplagiochin- and marchantin-class structures, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The structure–activity relationships and the results of molecular dynamics simulations indicated that bis(bibenzyl)s with potent anti-MRSA activity commonly have a 4-hydroxyl group at the D-benzene ring and a 2-hydroxyl group at the C-benzene ring in the hydrophilic part of the molecule, and an unsubstituted phenoxyphenyl group in the hydrophobic part of the molecule containing the A–B-benzene rings. Pharmacological characterization of the bis(bibenzyl) derivatives and 2-phenoxyphenol fragment 25, previously proposed as the minimum structure of riccardin C 1 for anti-MRSA activity, indicated that they have different action mechanisms: the bis(bibenzyl)s are bactericidal, while 25 is bacteriostatic, showing only weak bactericidal activity.     

Physical State in Which Naphthalene and Bibenzyl are Utilized by Bacteria

The generation times of a strain of Pseudomonas grown on a mineral salts medium in the presence of various amounts of naphthalene did not vary with the amount of solid present, and these generation times were the same as the generation time on mineral salts medium containing only dissolved naphthalene. The generation time of a soil isolate grown on mineral salts medium in the presence of 0.5 g of solid bibenzyl per liter was the same as the generation time on a mineral salts medium saturated with bibenzyl. The evidence indicates that naphthalene and bibenzyl are utilized in the dissolved state.     

Phenolic constituents of Coelogyne ovalis

The structure of 3′-O-methylbatatasin III, a new bibenzyl of the East Himalayan orchid, Coelogyne ovalis, has been established on the basis of spectral and chemical data. Known 9,10-dihydrophenanthrene derivatives, a bibenzyl and sterols have also been isolated from the orchid.     

Antifungal dibenzofuran bis(bibenzyl)s from the liverwort Asterella angusta

Bioactivity-guided separation of an antifungal extract from the liverwort Asterella angusta afforded four bis(bibenzyl)s, asterelin A (1), asterelin B (2), 11-O-demethyl marchantin I (3), and dihydroptychantol A (4), together with six known ones. Their structures were established by extensive spectroscopic analysis (1D and 2D-NMR, MS), and that of 2 was confirmed by X-ray crystallographic diffraction analysis. Compounds 1 and 2 are the first examples of dibenzofuran bis(bibenzyl)s. The antifungal activity of the isolated bis(bibenzyl)s against the common clinical pathogenic fungus Candida albicans was evaluated using both the thin-layer chromatography bioautographic assay and the broth microdilution method. They showed moderate antifungal activities with minimal inhibitory concentration (MIC) values ranging from 16 microg/ml to 512 microg/ml.     

细茎石斛的化学成分

从兰科植物细茎石斛(Dendrobium moniliforme(L.)Sw.)中分得一个新的联苄类化合物(moniliformine),以及6个已知化合物(α-dihydropicrotoxinin、对羟基顺式肉桂酸三十烷基酯、反式阿魏酸二十八烷基酯、β-谷甾醇、胡萝卜苷和二十九烷烃),经光谱解析(UV、IR、MS、1H-NMR、13C-NMR、DEPT、HMQC和COLOC),新化合物的结构被确定为3,4-二羟基-5,4'-二甲氧基联苄(3,4-dihydroxy-5,4'-dimemoxy bibenzyl).α-dihydropicrotoxinin为首次从自然界分离得到.     

Bibenzyls from Radula tokiensis and R. Japonica

A new bibenzyl having a dihydrooxepin ring was isolated from the acetone extract of the liverwort Radula tokiensis, together with the previously known 5 bibenzyls and 3 sesquiterpenes, trans-β-farnesene, cuparene and (Jcuparenol. Two known bibenzyls were isolated from R. japonica. The bibenzyl derivatives are significant chemosystematic markers of the Radulaceae.     

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A–G (1–7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9–21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC₅₀ values ranging from 2.2 to 21.2 μM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases.     

Eremophilanolides and other constituents from the Argentine liverwort Frullania brasiliensis.

Two eremophilanolides, 5-epidilatanolides A and B, as well as a new natural bibenzyl were isolated from an Argentine collection of the liverwort Frullania brasiliensis, along with the known eudesmane-type sesquiterpene lactones nepalensolide A, nepalensolide B, (+)-frullanolide, and (+)-dihydrofrullanolide, the hopanoid zeorin, the four sterols stigmasta-4,22-dien-3,6-dione, stigmasta-4,22-dien-3-one, stigmasterol, and sitosterol, and a trace amount of atraric acid. The structure and stereochemistry of the eremophilanolides and the bibenzyl were established by a combination of extensive NMR spectroscopy experiments and X-ray crystallographic analysis. Absolute configurations of the new compounds were derived on the basis of CD spectra.     

Bibenzyls and dihydroisocoumarins from white salsify (Tragopogon porrifolius subsp. porrifolius)

A phytochemical investigation of three accessions of Tragopogon porrifolius L. subsp. porrifolius (Asteraceae, Lactuceae) yielded three new bibenzyl derivatives, 5,4'-dihydroxy-3-alpha-l-rhamnopyranosyl-(1-->3)-beta-d-xylopyranosyloxybibenzyl, 2-carboxyl-3,4'-dihydroxy-5-beta-d-xylopyranosyloxybibenzyl, tragopogonic acid (2'carboxyl-3',5',4'-trihydroxyphenylethanone) and three dihydroisocoumarin derivatives, including the new natural product 6-O-methylscorzocreticoside I. One of the isolated bibenzyl derivatives is considered to be a precursor to the biosynthesis of dihydroisocoumarins. Structures of new compounds were established by HR mass spectrometry, extensive 1D and 2D NMR spectroscopy, and CD spectroscopy. Moreover, radical scavenging activities of the polyphenolic compounds were measured using the 2,2-diphenyl-1-picrylhydrazyl assay; two of the bibenzyls showed moderate and two of the dihydroisocoumarins showed weak radical scavenging activities. The chemosystematic impact of bibenzyls and dihydroisocoumarins is discussed briefly.     

Moscatilin,a bibenzyl derivative from the orchid Dendrobium moscatum

Moscatilin, a new bibenzyl derivative isolated from the orchid Dendrobium moscatum, was shown to have the structure 4,4′-dihydroxy-3,3′,5-trimethoxybibenzyl.     

New Cytotoxic Bibenzyl and Other Constituents from Bauhinia ungulata L. (Fabaceae)

A new bibenzyl, 2′‐hydroxy‐3,5‐dimethoxy‐4‐methylbibenzyl ( 1 ) and four known compounds identified as 2′‐hydroxy‐3,5‐dimethoxybibenzyl ( 2 ), liquiritigenin ( 3 ), guibourtinidol ( 4 ) and fisetinidol ( 5 ) were isolated from the roots of Bauhinia ungulata L. Phytochemical investigations of the stems of B. ungulata led to the isolation of the known compounds identified as liquiritigenin ( 3 ), guibourtinidol ( 4 ), fisetinidol ( 5 ), taraxerol ( 6 ), betulinic acid ( 7 ), taraxerone ( 8 ), glutinol ( 9 ), a mixture of sitosterol ( 10 ) and stigmasterol ( 11 ), pacharin ( 12 ), naringenin ( 13 ) and eriodictyol ( 14 ). The structures of these compounds were elucidated on the basis of their spectral data (IR, MS, 1D‐ and 2D‐NMR). The cytotoxicity of the bibenzyl 1 has been evaluated against four human cancer cell lines, showing the IC₅₀ values of 4.3 and 6.5 μg ml^?1 against pro‐myelocytic leukemia (HL‐60) and cervical adenocarcinoma (HEP‐2) cell lines, respectively. This article also registers for the first time the ¹³C‐NMR data of the known bibenzyl 2 .     

Amorfrutin A and B,bibenzyl antimicrobial agents from Amorpha fruticosa

Bioassay directed fractionation of the waxy fractions derived from the fruit of Amorpha fruticosa resulted in the isolation of amorfrutin A and B, active new antimicrobial agents. Spectroscopic studies, chemical degradation and synthesis showed them to be new bibenzyl metabolites.     

Inhibition of endothelial cell functions by novel potential cancer chemopreventive agents

Endothelial cells (EC) play a major role in tumor-induced neovascularization and bridge the gap between a microtumor and growth factors such as nutrients and oxygen supply required for expansion. Immortalized human microvascular endothelial cells (HMEC-1) were utilized to assess anti-endothelial effects of 10 novel potential cancer chemopreventive compounds from various sources that we have investigated previously in a human in vitro anti-angiogenic assay. These include the monoacylphloroglucinol isoaspidinol B, 1,2,5,7-tetrahydroxy-anthraquinone, peracetylated carnosic acid (PCA), isoxanthohumol, 2,2',4'-trimethoxychalcone, 3'-bromo-2,4-dimethoxychalcone as well as four synthetic derivatives of lunularic acid, a bibenzyl found in mosses [Int. J. Cancer Prev. 1 (2004) 47]. EC proliferation was inhibited with half-maximal inhibitory concentrations from 0.3 to 49.6muM, whereas EC migration was affected by most compounds at sub-micromolar concentrations. PCA and the bibenzyl derivative EC 1004 potently prevented differentiation of HMEC-1 into tubule-like structures. Overall, our data indicate that inhibition of endothelial cell function contributes to various extents to the chemopreventive or anti-angiogenic potential of these lead compounds.     

Riccardin C derivatives as anti-MRSA agents: Structure–activity relationship of a series of hydroxylated bis(bibenzyl)s

Members of a series of macrocyclic bis(bibenzyl) riccardin-class derivatives were found to exhibit antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure–activity relationship (SAR) studies were conducted, focusing on the number and position of the hydroxyl groups. The minimum essential structure for anti-MRSA activity was also investigated.     

Bibenzyl derivatives from Frullania Species

Four novel bibenzyl derivatives; 3,4,3′,4′-dimethylenedioxybibenzyl, 3,3′-dimethoxy-4,5-methylene-dioxybibenzyl,3,3'-dimethoxy-4,5-methylenedioxy-4′-hydroxybibenzyl and 3,3′-dihydroxy-4,5,4′,5′-dimethylenedioxybibenzyl were isolated from three Frullania species of liverworts and their structures were determined by spectral evidence and synthesis.     

A new bibenzyl from Dendrobium secundum

From the aerial parts of Dendrobium secundum, a new bibenzyl, namely 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl, was isolated, along with four known compounds which included brittonin A, moscatilin, syringaresinol, and ferulic acid. All of these isolates showed appreciable DPPH free radical scavenging potential, except for brittonin A, which was devoid of activity.     

Riccardin C,a novel cyclic bibenzyl derivative from Reboulia hemisphaerica

Riccardin C, a novel cyclic bibenzyl derivative with a biphenyl ether and biphenyl linkages, and the previously known ent-aristolone have been isolated from the liverwort Reboulia hemisphaerica. Riccardin C trimethyl ether was identical to the dimethoxy derivative of riccardin A isolated from the liverwort Riccardia multifida.     

Phenolic compounds from the rhizomes of Dioscorea bulbifera

One new bibenzyl, 7, and one new diarylheptanone, diobulbinone A (18), together with sixteen known compounds, 1-6 and 8-17, have been isolated form the rhizomes of Dioscorea bulbifera. Their structures were elucidated by NMR and MS analyses. Compound 7 showed high antioxidant capacity in FRAP assay and DPPH radical-scavenging activity.     

Corsifurans A-C, 2-arylbenzofurans of presumed stilbenoid origin from Corsinia coriandrina (Hepaticae)

Chemical investigation of the diethyl ether extract from the liverwort Corsinia coriandrina resulted in the isolation of a new 2-arylbenzofuran compound called corsifuran A. The structure was identified by spectroscopic techniques and confirmed by synthesis. Two minor constituents of similar structure, and two related stilbenoids and a bibenzyl were identified by comparison of the mass spectra and GC retention indices with authentic samples. Due to the similarity in substitution patterns a stilbenoid origin of the corsifurans is proposed.     

Molecular design of potent tyrosinase inhibitors having the bibenzyl skeleton

In order to develop water soluble tyrosinase inhibitors, bibenzyl xyloside 1 isolated from Chlorophytum arundinaceum (liliaceae), and its derivatives 2 and 3 were synthesized by using Wittig reaction and trichloroimidate glycosylation procedure as key steps. Xylosides 1-3 showed potent tyrosinase inhibitory activity with IC(50)s of 1.6, 0.43, and 0.73 microM, respectively, although each NMR data of synthetic bibenzyls was not identical to that of naturally occurring xyloside 1.