Discovery of prenylated indole alkaloid and natural xanthone from cold-seep sediment derived fungus Talaromyces funiculosus SD-523

A new prenylated indole alkaloid 11,17-epi-mangrovamide A(1),a new natural occurring product,1,7-dihydroxy-6-methyl-8-hydroxymethyl-xanthone(2),two known alkaloids,mangrovamide A(3)and mangrovamide G(4),and four known polyketide derivatives(5–8)were isolated and identified from the cold-seep sediment derived fungal strain Talaromyces funiculosus SD-523.Their structures were elucidated by combination of nuclear magnetic resonance(NMR),high resolution electrospray ionization mass spectroscopy(HRESIMS),quantum chemical electronic circular dichroism(ECD),and DP4+probability analysis as well as by comparison of the data with literature reports.All isolated compounds were tested for antibacterial activities.

A new prenylated arylbenzofuran derivative from Morus alba L.

2-[3,5-Di-O-β-D-glucosyl-4-(3-methylbut-2-enyl)phenyl]benzofuran-6-ol,a new prenylated arylbenzofuran derivative was isolated from Morus alba L.Its structure was elucidated by various spectroscopic methods including MS,~1H NMR,^(13)C NMR,DEPT,~1H-~1HCOSY,HMQC and HMBC.

ISOLATION, STRUCTURE ELUCIDATION AND SYNTHESIS OF A NEW PRENYLATED FLAVONOL, MAACKIAFLAVONOL, FROM MAACKIA TENUIFOLIA

A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, IR, MS, NMR and 1H-1H COSY) and confirmed by total synthesis.

Prenylated flavonoids from Tephrosia apollinea

In continuation of our chemical investigation on some medicinal plants of the genus Tephrosia, re-investigation of the methylenechloride/methanol （1：1） extract of the air-dried aerial part of Tephrosia apollinea afforded a new prenylated flavonoid 1, in addition to an aromatic ester, a sesquiterpene, a lignan and several known prenylated flavonoids. The structures were established by （^1H NMR, ^13C NMR, DEPT, ^1H-^1H COSY, HMQC, HMBC, NOESY and HRMS）. Relative configurations of 9 and 10 were confirmed by X-ray analysis.

Prenylated Coumarins from Heracleum stenopterum,Peucedanum praeruptorum,Clausena lansium,and Murraya paniculata

Four hitherto unknown prenylated coumarins,namely 600-O-b-D-apiofuranosylapterin(1),40-O-isobutyroylpeguangxienin(2),6-(3-methyl-2-oxobutyroyl)-7-methoxycoumarin(3),and 6-hydroxycoumurrayin(4),were isolated from the ethanol extract of Heracleum stenopterum,Peucedanum praeruptorum,Clausena lansium,and Murraya paniculata,respectively.Their chemical structures were established on the basis of extensive spectroscopic analysis.Compound 2 exhibited in vitro cytotoxic activity against five human cancer cell lines(HL-60,A-549,SMMC-7721,MCF-7,and SW-480)with IC50 values ranging from 15.9 to 23.2μM.

Pyrohyperforin, A New Prenylated Phloroglucinol from Hypericum perforatum

Pyrohyperforin, a new prenylated phloroglucinol was isolated from Hypericum perforatum, its structure was established on the basis of spectral data.

Minor Prenylated Flavonoids from the Twigs of Macaranga adenantha and Their Cytotoxic Activity

Three new minor prenylated flavonoids,named macadenanthins A–C(1–3),together with three known ones(4–6),were isolated from the twigs of Macaranga adenantha.Their structures were elucidated on the basis of extensive spectroscopic analysis including NMR,UV and MS.The prenyl moieties in compounds 1–3 were further modified by cyclization and hydroxylation.The new compounds were tested for their cytotoxicity against four cancer cell lines(MCF-7,Hep G2,Hela and P388)and showed IC50 values in the range of 13.76–22.27 lM.

New Prenylated flavonol from Hypericum japonicum

One new prenylated flavonol, 7,8-(2'',2'' -dimethylpyrano)-5,3',4'-trihydroxy-3-methoxyflavone was isolated from Hypericum japonicum. The chemical structure was determined by spectroscopic methods.

A new bioactive prenylated dihydroflavanoid from Dolichos tenuicaulis (Baker) Craib

A new prenylated dihydroflavonoid was obtained from the root of Dolichos tenuicaulis （Baker） Craib. The structure was elucidated as （2S）-5,2＇,6＇-trihydroxy-3＇″, 8-di （γ,γ-dimethyl-allyl）-2＇″, 2＇″-dimethylpyrano-[5＇″,6＇″： 6,7]-2＇″″,4＇″″-cyclohexadiene-1 ＇″″-one-[2＇″″,3＇″″： 3＇,4＇]-flavanone, named dolichnin A, by spectroscopic methods including UV, IR, HR-EI-MS, 1D NMR and 2D NMR techniques, and subsequently, the anticancer activity of this compound to inhibit human cancer cells＇ growth including A549, BEL-7402, Hep-3B, SMMC7721, HT-29, MCF-7, SGC-7902, K562, A498 and PC3 cell lines by MTT method was evaluated in vitro.

Geranylated or prenylated flavonoids from Cajanus volubilis

Five new flavonoid derivatives,cajavolubones A-E(1-5),along with six known analogues(6-11)were isolated from Cajanus volubilis,and their structures were elucidated by spectroscopic analysis and quantum chemical calculations.Cajavolubones A and B(1 and 2)were identified as two geranylated chalcones.Cajavolubone C(3)was a prenylated flavone,while cajavolubones D and E(4 and 5)were two prenylated isoflavanones.Compounds 3,8,9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.

Prenylated flavonoids from Glycyrrhiza uralensis as promising anti-cancer agents: a preliminary structure-activity study

Prenylated flavonoids are mainly distributed in Leguminosae and Moraceae plants, and they have been reported to possess various biological activities. Previously, we have reported a prenylated isoflavonoid, isoangustone A（IAA） from licorice（Glycyrrhiza uralensis）, which induces apoptosis in colorectal cancer cells by disrupting mitochondrial functions. In the present study, we compared a group of flavonoids from licorice with IAA for their anti-proliferation activities and effects on intracellular signaling. The results indicated that the isoprenyl groups on the A and B rings, the hydroxyl groups at the ortho position of isoprenyl on A ring and the conjugated plane of C ring might contribute to the anti-cancer activity of prenylated flavonoids. Based on the above structure-activity relationship, we further identified four prenylated flavonoids with similar anti-cancer activities from licorice. Taken together, our present study established a preliminary structure-activity relationship of anti-cancer prenylated flavonoids, and our data provided important leading compounds from licorice, which deserved further research and development.

New prenylated flavonoid glycosides derived from Epimedium wushanense byβ-glucosidase hydrolysis and their testosterone production-promoting effects

Six new prenylated flavonoid glycosides,including four new furan-flavonoid glycosides wushepimedoside A–D(1–4)and two new prenyl flavonoid derivatives wushepimedoside E–F(5–6),and one know analog epimedkoreside B(7)were isolated from biotransformation products of the aerial parts of Epimedium wushanense.Their structures were elucidated according to comprehensive analysis of HR-MS and NMR spectroscopic data,and the absolute configurations were assigned using experimental and calculated electronic circular dichroism(ECD)data.The regulatory activity of compounds 1–7 on the production of testosterone in primary rat Leydig cells were investigated,and 4 and 5 exhibited testosterone production-promoting activities.Molecular docking analysis suggested that bioactive compounds 4 and 5 showed the stable binding with 3β-HSD and 4 also had good affinity with Cyp17A1,which suggested that these compounds may regulate testosterone production through stimulating the expression of the above two key proteins.

Synthesis and pharmacological properties of naturally occurring prenylated and pyranochalcones as potent anti-inflammatory agents

An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.

Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis, dehydrogenation, selective O-methylation, O-prenylation and Claisen rearrangement reaction, from abundant and inexpensive natural flavonoids naringin, hespiredin, quercetin and myricetin. Among them, 1-7, 10-15 and 17-20 are novel compounds, the natural product 3,3＇,4＇,7-tetramethoxy-8-prenyl-5-hydroxy flavonoid（16） was synthesized in a high yield. Their antiprolirative activities were evaluated in vitro on a panel of three human cancer cell lines（HeLa, HCC1954 and SK-OV-3）. The results show that most of the target compounds displayed moderate to potent antiprolirative activities against the three cancer cells with half maximal inhibitory concentration（ICs0） values from 0.49 μmol/L to 95.07 μmol/L. Among them, 3′,4′,7-trimethoxyl-5-hydroxyl-8-prenyl flavonoid（12） exhibited the strongest antiprolirative activity against the three cancer cells mentioned above with IC50 values of 0.91-7.08 μmol/L. 3′,7-Dimethoxy-5-O- prenyl flavone（6） and 3′,4′,7-trimethoxy-5-O-prenyl flavone（10） showed selective antiproliferative activity against HCC1954 cells with TC50 value of 0 49 and 5 .32μmol/L, respectively.

A New Prenylated Xanthone from Root Barks of Cudrania cochinchinensis

Objective To study the chemical constituents from the root barks of Cudrania cochinchinensis. Methods The chemical constituents were isolated and purified by silica gel column chromatography. The structures of the compounds were identified on the basis of spectral data(MS,1H-NMR,13C-NMR, and 2D NMR) and by the comparison of spectroscopic data with the reported values in the literatures. Results A new xanthone, 1,6,7-trihydroxy-4-(1,1-dimethylallyl)-3-methoxyxanthone(1) and a known prenylated xanthone 1,5,6-trihydroxy-4-(1,1-dimethylallyl)-3-methoxyxanthone(isocudraniaxanthone B, 2) were isolated from the root barks of C. cochinchinensis. Conclusion Compound 1 is a new prenylated xanthone. Isomers 1 and 2 are obtained from this plant for the first time.

Two New Dihydroflavanoids from Patrinia villosa Juss

Two new dihydroflavonoids were obtained from the traditional Chinese medicinal herb Patrinia villosa Juss. Their structures were elucidated as （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6, 8-di （γ, γ-dimethylallyl） flavanone （1） and （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6-1avandulylated flavanone （2） by spectroscopic methods including UV, IR, HR-TOF-MS, 1D NMR and 2D NMR techniques.

Do statins reduce hepatitis C RNA titers during routine clinical use?

AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).METHODS: Medical records were reviewed for 6463 patients with documented HCV infection at a single center between March 2004 and September 2006. Patients with confi rmed viremia and meeting inclusion criteria were assigned to one of three groups: Group A (n = 50), dyslipidemic patients with statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group B (n = 49), dyslipidemic patients with prior or future statin usage but not at the time of HCV RNA PCR determination; and Group C (n = 102), patients without statin usage during the study period. The primary analysis explored the effect of statin therapy on HCV viremia. Secondary analyses assessed class effect, dose response, and effect of other lipid-lowering therapies on HCV viral titers.RESULTS: Median HCV RNA titers did not signif icantly differ among the three groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000 IU/mL).For those subjects with longitudinal assessment of HCV viremia prior to and while on statins, there were no signif icant differences between pre- and post-HCV viral titers. Additionally, no differences in HCV titers were observed at any dose level of the most prescribed statin, simvastatin. However, hypertriglyceridemia independently correlated with HCV titers, and niacin exposure was associated with signif icantly lower viral titers (P < 0.05).CONCLUSION: There was no apparent effect of statins on HCV viral replication in this analysis. Further investigation is warranted to explore the possible antiviral properties of triglyceride-lowering agents and their potential role as adjuncts to standard HCV therapy.

Three new compounds from the leaves of Acanthopanax senticosus Harms

Three new compounds named (2E)prenyl benzoate-4-O-α-L-arabinopyranosyl (1→6) β-D-glucopyranoside (1), 7-methoxy-8-O-β-D-glucopyranosyl coumarin (2), and 3,4'-dihydroxy-3'-methoxy benzenepentanoic acid (3) were isolated from the leaves of Acanthopanax senticosus Harms. The structures of new compounds were determined by means of 2D NMR experiments and chemical methods.

Synthesis of Bioactive Natural Polymethoxyflavones and Their Vinyl Ether Derivatives

Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.

TWO NEM IS0PRENYL PLAVONOIDS FROM THE LEAVES OP GLYCYRRHIZA URALENSIS FISOH

Three flavonoids have been isolated from the leaves of Glycyrrhiza uralensis Fisch(licorice,Leguminosae).The structures have been identified as 5,7,3',4'-tetrahydroxy-3-methoxy-5'-isoprenyl flavone(I,uralenol-3-methylether),5,6,3',4'-tetrahydroxy-3-methoxy-6'-isoprenyl flavone (Ⅱ, unalene) and quercetin(Ⅲ).Ⅰ and Ⅱ are new compound.