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1 H NMR-guided fractionation of the petroleum ether extract of the aerial parts from Hypericum hirsutum yielded to the isolation of 19 polyprenylated polycyclic acylphloroglucinols. Structure elucidation based on 1D and 2D NMR spectroscopy together with high-resolution electrospray ionization mass spectroscopy revealed 14 acylphloroglucinols with a homoadamantane scaffold (1 – 14), while 5 further compounds showed an adamantane skeleton (15 – 19). Except for hookerione C (15), all isolated metabolites are hitherto unknown. While structurally-related metabolites have been isolated from other Hypericum species, it is the first report of admantan and homoadamantan type acylphloroglucinols in section Taeniocarpium Jaub. & Spach (Hypericaceae). The isolated compounds have been tested in a crystal violet-based in vitro assay on their properties to reduce the proliferation of human microvascular endothelial cells compared to hyperforin as the positive control. They showed a moderate reduction of proliferation with IC50 values in the range ~ 3 – 22 µM, with the homoadamantane-based compounds 2 and 4 being the most active. In addition, inhibition of the TNF- α -induced ICAM-1 expression was determined for 1 – 5, 7, and 10 – 12. Substances 3 and 12 reduced the ICAM-1 expression significantly (to 46.7% of control for 3 , 62.3% for 12, at 50 µM). [ABSTRACT FROM AUTHOR]

1 H NMR-guided fractionation of the petroleum ether extract of the aerial parts from Hypericum hirsutum yielded to the isolation of 19 polyprenylated polycyclic acylphloroglucinols. Structure elucidation based on 1D and 2D NMR spectroscopy together with high-resolution electrospray ionization mass spectroscopy revealed 14 acylphloroglucinols with a homoadamantane scaffold (1 – 14), while 5 further compounds showed an adamantane skeleton (15 – 19). Except for hookerione C (15), all isolated metabolites are hitherto unknown. While structurally-related metabolites have been isolated from other Hypericum species, it is the first report of admantan and homoadamantan type acylphloroglucinols in section Taeniocarpium Jaub. & Spach (Hypericaceae). The isolated compounds have been tested in a crystal violet-based in vitro assay on their properties to reduce the proliferation of human microvascular endothelial cells compared to hyperforin as the positive control. They showed a moderate reduction of proliferation with IC50 values in the range ~ 3 – 22 µM, with the homoadamantane-based compounds 2 and 4 being the most active. In addition, inhibition of the TNF- α -induced ICAM-1 expression was determined for 1 – 5, 7, and 10 – 12. Substances 3 and 12 reduced the ICAM-1 expression significantly (to 46.7% of control for 3 , 62.3% for 12, at 50 µM). [ABSTRACT FROM AUTHOR]

Thirteen prenylated acylphloroglucinols (1 – 13), including 2 previously undescribed compounds (1) and (2), were isolated from Hypericum jovis. Their structures were elucidated by high-field NMR spectroscopy. The isolated prenylated acylphloroglucinols were evaluated for their anti-inflammatory effects in vitro through the reduction of the intercellular adhesion molecule 1 expression induced by TNF- α in the human microvascular endothelial cells 1 cell line. Compounds 3, 5, 6, 8, and 12 significantly reduced intercellular adhesion molecule 1 expression in a concentration-dependent manner with IC50 values of 16.9, 34.4, 4.0, 3.2, and 7.7 µM, respectively. In addition, compound 12 showed notable inhibitory activity on the formation of cyclooxygenase-1- and 12-lipoxygenase-derived inflammatory mediators in an ex vivo cyclooxygenase-lipoxygenase assay. Eleven further constituents were isolated (14 – 24), including the rare quercetin 3-O-(2-O-acetyl)-arabinofuranoside (18). [ABSTRACT FROM AUTHOR]

Flavonoid glycosides are extensively metabolized to glucuronidated compounds after oral intake. Recently, a cleavage of quercetin glucuronides by β-glucuronidase has been found. To characterize the deglucuronidation reaction and its structural prerequisites among the flavonoid subtypes more precisely, four flavonol glucuronides with varying glucuronidation positions, five flavone 7-O-glu-curonides with varying A- and B-ring substitution as well as one flavanone- and one isoflavone-7-O-glucuronide were analyzed in a human mono-cytic cell line. Investigation of the deglucuronidation rates by HPLC revealed a significant influence of the glucuronidation position on enzyme activity for flavonols. Across the flavonoid subtypes, the C-ring saturation also showed a significant influence on deglucuronidation, whereas A- and Bring variations within the flavone-7-O-glucuro-nides did not affect the enzymes' activity. Results were compared to computational binding studies on human β-glucuronidase. Additionally, molecular modeling and dynamic studies were performed to obtain detailed insight into the binding and cleavage mode of the substrate at the active site of the human β-glucuronidase. [ABSTRACT FROM AUTHOR]

Two tetrahydroxanthene-1,3(2H)-dione metabolites, valderramenols A (1) and B (2), were isolated from the Philippine endemic Annonaceous species Uvaria valderramensis. Planar structures of the rac-xanthene-1,3-(2H)-diones 1and 2were established by MS and NMR measurements. Their enantiomers were separated by chiral HPLC, and the absolute configurations of the separated enantiomers were determined by comparison of the HPLC-ECD spectra with computed TDDFT-generated spectra. A TDDFT-ECD study of the known grandiuvarone (3) allowed the revision of its absolute configuration as S. Compound 1showed antitubercular activity (MIC 10 μg/mL), while 3and 4had weaker activities (MIC 32 μg/mL). Oxepinone 3exhibited cytotoxic activity against KB-562, a chronic myeloid leukemia cell line.

A strategy for the synthesis of natural and non-natural 5-deoxy-6,7-dihydrocurcuminoids (diarylheptanoids) was developed for the preparation of 14 compounds with varying aromatic substituent patterns and a different functionality in the aliphatic seven-carbon chain. The in vitro protective activity against glutamate-induced neuronal cell death was examined in the murine hippocampal cell line HT-22 to find structural motifs responsible for neuroprotective effects in vitro. Among the tested compounds the ferulic acid-like unit, present in the structures of (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-en-3-one (5) and (E)-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hept-1-en-3-one (7), appeared to be an important feature for protection against glutamate-induced neurotoxicity. Both compounds demonstrated significant neuroprotective activity in a concentration range between 1 and 25 μM without showing toxic effects in a cytotoxicity assay with HT-22 cells. Furthermore, (E)-1,7-bis(3,4-dihydroxyphenyl)hept-1-en-3-one (9), exhibiting a caffeic acid-like structural motif, displayed a neuroprotective activity at a nontoxic concentration of 25 μM. In contrast, (1E,6E)-1,7-bis(3,4-dihydroxyphenyl)hepta-1,6-diene-3,5-dione (4, di-O-demethylcurcumin) showed mainly cytotoxic effects. A corresponding single-ring analogue that contains the ferulic acid-like unit as an enone was not active.

A real-time and label-free in vitro assay based on electric cell-substrate impedance sensing (ECIS) was established, validated, and compared to an end-point MTT assay within an experimental trial addressing the cytoprotective effects of 19 different flavonoids, flavonoid metabolites, and phenolic acids and their methyl esters on the HT-22 neuronal cell line, after induction of oxidative stress with tert-butyl hydroperoxide. Among the flavonoids under study, only those with a catechol unit and an additional 4-keto group provided cytoprotection. The presence of a 2,3-double bond was not a structural prerequisite for a neuroprotective effect. In the case of the phenolics, catechol substitution was the only structural requirement for activity. The flavonoids and other phenolics with a ferulic acid substitution or a single hydroxy group showed no activity. Electrochemical characterization of all compounds via square-wave voltammetry provided a rather specific correlation between cytoprotective activity and redox potential for the active flavonoids, but not for the active phenolics with a low molecular weight. Moreover this study was used to compare label-free ECIS recordings with results of the established MTT assay. Whereas the former provides time-resolved and thus entirely unbiased information on changes of cell morphology that are unequivocally associated with cell death, the latter requires predefined exposure times and a strict causality between metabolic activity and cell death. However, MTT assays are based on standard lab equipment and provide a more economic way to higher throughput.

After oral administration of 100mg/kg b.w. (235.8 µmol/kg) salicortin to Wistar rats, peak serum concentrations of 1.43 mg/L (13.0 µM) catechol were detected after 0.5 h in addition to salicylic acid by HPLC-DAD after serum processing with β-glucuronidase and sulphatase. Both metabolites could also be detected in the serum of healthy volunteers following oral administration of a willow bark extract (Salicis cortex, Salix spec. Salicaceae) corresponding to 240 mg of salicin after processing with both enzymes. In humans, the cmax (1.46 mg/L, 13.3 µM) of catechol was reached after 1.2 h. The predominant phase-II metabolite in humans and rats was catechol sulphate, determined by HPLC analysis of serum samples processed with only one kind of enzyme. Without serum processing with glucuronidase and sulphatase, no unconjugated catechol could be detected in human and animal serum samples. As catechol is described as an anti-inflammatory compound, these results may contribute to the elucidation of the mechanism of the action of willow bark extract. [ABSTRACT FROM AUTHOR]

The 1H NMR-guided fractionation of a petroleum ether extract of Hypericum empetrifoliumled to the isolation of four new bicyclic (1–4), four known bicyclic (5–8), three new tricyclic (9–11), and three new polycyclic acylphloroglucinols (12/13and 14) possessing a monoterpenoid citran moiety. Compounds 12/13were isolated as a mixture of two inseparable structural isomers. The compounds showed in vitro antiproliferative activity against human microvascular endothelial cells (HMEC-1) with IC50values in the range 9.2 ± 2.0 to 29.6 ± 3.5 μM.

Therapeutic effects of dietary flavonoids have been attributed mainly to their antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant, Humulus lupulus, was investigated for its antioxidant potential and for its effect on NF-κB activation. To examine the biological relevance of 1, a hepatic ischemia/reperfusion model was chosen as a widely accepted model of oxidative stress generation. The impact of 1on endogenous antioxidant systems, on the NF-κB signal transduction pathway as well as on apoptotic parameters, and on hepatic tissue damage was evaluated. Compound 1markedly decreased the level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated. NF-κB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon pretreatment with 1. In addition, the phosphorylation of Akt was markedly inhibited. Surprisingly, 1decreased the expression of the antiapoptotic protein Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover, hepatic tissue damage as well as TNF-α levels increased in xanthohumol-pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did not protect against ischemia/reperfusion injury in rat liver, despite its antioxidant and NF-κB inhibitory properties.

Despite its popularity and widespread use, the efficacy of Echinaceaproducts remains unclear and controversial. Among the various compounds isolated from Echinacea, ketoalkenes and ketoalkenynes exclusively found in the pale purple coneflower (E. pallida) are major components of the extracts. In contrast to E. purpureaalkamides, these compounds have not been synthesized and studied for immunostimulatory effects. We present a practical and useful synthetic approach to the ketoalkenes using palladium‐catalyzed cross‐coupling reactions and the pharmaceutical results at the human cannabinoid receptors. The synthetic route developed provides overall good yields for the ketoalkenes and is applicable to other natural products with similar 1,4‐diene motifs. No significant activity was observed at either receptor, indicating that the ketoalkenes from E. pallidaare not responsible for immunomodulatory effects mediated via the cannabinergic system. However, newly synthesized non‐natural analogues showed micro‐molar potency at both cannabinoid receptors.

The minor hop ( Humulus lupulus) chalcones 3′-geranylchalconaringenin ( 3), 5′-prenylxanthohumol ( 4), flavokawin ( 5), xanthohumol H ( 8), xanthohumol C ( 9), and 1′′,2′′-dihydroxanthohumol C ( 10) were synthesized. The non-natural chalcones 3′-geranyl-6′- O-methylchalconaringenin ( 2), 3′-methylflavokawin ( 6), and 2′- O-methyl-3′-prenylchalconaringenin ( 7) were also synthesized. Cytotoxicity was investigated in HeLa cells, and these compounds all had IC 50values comparable to xanthohumol (8.2−19.2 μM). The ORAC-fluorescein assay revealed potent antioxidative activity for 7and 8with 5.2 and 4.8 Trolox equivalents, respectively.

Im Bereich der Wirkstoffsuche sind Naturstoffe unverzichtbar. Problematisch bei der Gewinnung von Naturstoffen sind die Beschaffung des biologischen Materials, die Auffindung und Isolierung aus einer inaktiven oder sogar die biologische Testung störenden Matrix und die Gewinnung ausreichender Mengen zur chemischen und pharmakologischen Charakterisierung bzw. für die klinische Nutzung. Oft stellen Naturstoffe ideale Leitstrukturen für die synthetische oder semisynthetische Entwicklung von Wirkstoffen dar. Besonders attraktiv sind Naturstoffe dann, wenn die biologische Quelle erneuerbar bzw. sogar in Kultur modifizierbar ist. Dies ist ein wesentlicher Aspekt für die gegenwärtige Attraktivität der Wirkstoffsuche in Mikroorganismen wie Bakterien und Pilzen. Diese können im Idealfall nicht nur in Fermentern kultiviert, sondern dort auch genetisch so verändert werden, dass neuartige Strukturen entstehen.

From the aerial parts of Anthemis tinctoria L. subsp. tinctoria var. pallida DC. (Asteraceae), one new cyclitol glucoside, conduritol F-1-O-(6′-O-E-p-caffeoyl)-β-d-glucopyranoside (1), has been isolated together with four flavonoids, nicotiflorin (2), isoquercitrin (3), rutin (4) and patulitrin (5). The structures of the isolated compounds were established by means of NMR, MS, and UV spectral analyses. Methanolic extract and pure isolated compounds were examined for their free radical, scavenging activity, using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free stable radical, and for their inhibitory activity toward soybean lipoxygenase, using linoleic acid as substrate. Compounds 1 and 5 showed a strong scavenging effect in the DPPH radical assay. In addition 5 also exhibited high inhibitory activity on soybean lipoxygenase.

Together with ten well known compounds, the quinic acid derivative chlorogenic acid, the nucleoside adenosine, two amino acids, tryptophan and phenylalanine, the anthraquinone derivatives, aloemodin, aloemodin acetate and chyrosphanol 1-O-gentiobioside, the flavon C-glycosides, isovitexin, isoorientin and isoorientin 4’-O-β -glucopyranoside, as well as two new acylated isoorientin derivatives, 6”-O-(malonyl)-isoorientin and 6”-O-[(S)-3-hydroxy-3-methylglutaroyl]-isoorientin, were isolated from the water soluble part of the methanolic extract of the fresh leaves of Asphodelus aestivus. All compounds were structurally identified by spectroscopic methods, including UV, MS, and NMR (1D and 2D) spectroscopy. Among the compounds isolated, chlorogenic acid and isoorientin were found to be the main compounds of the methanolic extract.

From the aerial parts of Ajuga salicifolia (L.) Schreber, a new ionone glycoside (3ß-hydroxy- 7,8-dihydro-4-oxo-ß-ionol-9-O-ß-?-glucopyranoside) was isolated, along with the known compounds, corchoionoside C, 8-O-acetylmioporoside, ajugol, harpagide, 8-O-acetylharpagide, lavandulifolioside and leonosides A and B. This is the first report of the occurrence of ionone glycosides and 8-O-acetylmioporoside in Ajuga species. Ajugol, lavandulifolioside, leonoside A and B were isolated for the first time from Ajuga salicifolia. The structures were elucidated by means of 1D-, 2D-NMR spectroscopy, and HR-MALDI mass spectrometry.

Purpose.Quantification of the pro-inflammatory action of mitogens on mRNA levels of growth-related genes, transcription factors, and cytokines in T cells as markers for the screening of compounds with immunomodulatory, anti-inflammatory or cytotoxic potential. Method.A reverse transcription-real time-polymerase chain reaction assay with TaqMan probes was developed. Jurkat T cells were treated with cyclosporin A, hypericin, capsaicin, and catechin before phorbol 12-myristate 13-acetate stimulation, and their effects on the relative mRNA levels were determined. A cell viability assay was performed in parallel. Results.Cyclosporin A and capsaicin were potent inhibitors of PMA-induced cytokine transcription. Cyclosporin A further targeted cyclin D1 transcription. Capsaicin exhibited no effects on the cell viability at low concentrations, whereas cyclosporin A did. Hypericin down-regulated nearly all investigated mRNAs, resulting in a strong time-dependent cytotoxicity. Catechin showed no effects on mRNA levels and cell viability. Conclusions.The inhibition of the up-regulation of mRNA levels of cytokines points to a specific anti-inflammatory potential of capsaicin. Hypericin showed no specific effects on the mRNA expression. The overall decrease of mRNA levels is probably an early indication of the strong cytotoxic effect observed after 48 h. Therefore, quantification of mRNA levels by reverse transcription-real time-polymerase chain reaction is, in combination with the monitoring of cell viability, a valuable tool to distinguish between specific immunomodulatory and cytotoxic effects in vitro.

In continuation of a previous QSAR study on the cytotoxicity of 20 sesquiterpene lactones (STLs) of the helenanolide type towards a mouse tumour cell line where a very strong correlation of activity with only two indicator variables encoding the nature of the present α,β-unsaturated carbonyl structure elements (cyclopentenone and α-methylene-γ-lactone structure) was found, it was the major goal of this study to establish a QSAR model for a set of STLs with wider structural variability. Cytotoxicity towards the human KB cervix carcinoma cell line was experimentally determined for a set of 40 STLs representing five different structural groups (2 germacranolides, 6 guaianolides, 23 pseudoguaianolides, 8 eudesmanolides and 1 carabranolide (cyclopropane type xanthanolide) and the resulting IC50 values were submitted to a QSAR study using the molecular modelling program MOE. As major result it could be shown that variance in STL cytotoxicity data can be explained to a high degree by electronic and surface properties. QSAR models of considerable internal and external predictivity could be obtained by PCR and PLS analysis of a descriptor set representing fractional accessible molecular surface areas (Q_frASAs). This set of descriptors is calculated by partitioning the molecular surface accessible to a spheric probe of radius 1.4 Å into fractions attributable to atoms within 14 charge intervals from −0.3 to 0.3 e. The applicability of such Q_frASA descriptors is validated by analysis of several sets of literature data, yielding QSAR models of good statistical quality. It is therefore assumed that Q_frASA descriptors may be of wider applicability in QSAR and QSPR.

Two novel and three new sterol glycosides were isolated from the MeOH extract of the aerial parts of Ajuga salicifolia (L.) Schreber. The structures of the compounds were elucidated as (3R,16S,17S,20R,22S,23S, 24S,25S)-16,23 : 16,27 : 22,25-triepoxy-3-(β-D-glucopyranosyloxy)coprostigmast-7-en-17-ol (1), (3R,16S,17S, 20R,22S,23S,24S,25S)-16,23 : 16,27 : 22,25-triepoxy-3-{[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]oxy}coprostigmast-7-en-17-ol (2), (3R,16S,17R,20S,22R,24S,25S)-22,25-epoxy-3,27-bis(β-D-glucopyranosyloxy)coprostigmast-7-en-16-ol (3), (3R,16S,17R,20S,22R,24S,25S)-22,25-epoxy-3-{[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]oxy}-27-(β-D-glucopyranosyloxy)coprostigmast-7-en-16-ol (4), and (3R,16R,17S,20R,22S,23S, 24S,25S)-22,25-epoxy-3-(β-D-glucopyranosyloxy)coprostigmast-7-ene-16,17,23,27-tetrol 27-acetate (5) by means of 1D and 2D NMR spectroscopy and HR-MALDI mass spectrometry. The novel compounds, which consist of three additional ring systems at the coprostigmastane skeleton, were named ajugasalicioside A (1) and B (2), and the new compounds C (3), D (4) and E (5). In our cytotoxicity assays (HeLa cells, Jurkat T cells, and peripheral mononuclear blood cells), ajugasaliciosides A–D specifically inhibited the viability and growth of Jurkat T-leukemia cells at concentrations below 10 μM. Ajugasalicioside A (1; (IC50=6 μM) and C (3; IC50=3 μM) were the most active compounds. Ajugasalicioside A (1) induced cell-cell contact, inhibited Jurkat T cell proliferation, and up-regulated mRNA levels of the cell-cycle regulator cyclin D1, which might be an indication for cell differentiation. Furthermore, 1 down-regulated the mRNA levels of the NF-κB subunit p65 in a concentration-dependent manner. These effects were not found for ajugasalicioside B (2), which has an additional glucose unit, and the onset of cytotoxicity of 2 (IC50=10 μM) was delayed by 24 h.

From the petroleum-ether extract of the dried aerial parts of Hypericum papuanum, three new prenylated tricyclic and four new bicyclic acylphloroglucinol derivatives were isolated by bioactivity-guided fractionation. The structures of the bicyclic compounds enaimeone A, B, and C (1/1a, 2/2a, and 3/3a, resp.) were elucidated as rel-(1R,5R,6S)-4-hydroxy-6-(1-hydroxy-1-methylethyl)-5-methyl-1-(3-methylbut-2-enyl)-3-(2-methylpropanoyl)-bicyclo[3.2.1]oct-3-ene-2,8-dione (1/1a), rel-(1R,5R,6R)-4-hydroxy-6-(1-hydroxy-1-methylethyl)-5-methyl-1-(3-methylbut-2-enyl)-3-(2-methylpropanoyl)bicyclo[3.2.1]oct-3-ene-2,8-dione (2/2a), rel-(1R,5R,6R)-4-hydroxy-6-(1-hydroxy-1-methylethyl)-5-methyl-3-(2-methylbutanoyl)-1-(3-methylbut-2-enyl)bicyclo[3.2.1]oct-3-ene-2,8-dione (3/3a). The tricyclic isolates 8-hydroxy-3β-(1-hydroxy-1-methylethyl)-4,4,7-trimethyl-9-(2-methylpropanoyl)-5βH-tricyclo[5.3.1.0^1,5]undec-8-ene-10,11-dione (4), 8-hydroxy-3α-(1-hydroxy-1-methylethyl)-4,4,7-trimethyl-9-(2-methylpropanoyl)-5βH-tricyclo[5.3.1.0^1,5]undec-8-ene-10,11-dione (5), and 8-hydroxy-3α-(1-hydroxy-1-methylethyl)-4,4,7-trimethyl-9-(2-methylbutanoyl)-5βH-tricyclo[5.3.1.0^1,5]undec-8-ene-10,11-dione (6), and their corresponding tautomers 4a, 5a, and 6a, were named 1'-hydroxyialibinones A, B, and D, respectively. Oxidative decomposition of furonewguinone A (=2,3,3a,5-tetrahydro-3a-hydroxy-2-(1-hydroxy-1-methylethyl)-5-methyl-5-(3-methylbut-2-enyl)-7-(2-methylpropanoyl)-benzofuran-4,6-dione; 7) led to furonewguinone B (=3,3a,7,7a-tetrahydro-3a,6,7a-trihydroxy-2-(1-hydroxy-1-methylethyl)-7-methyl-7-(3-methylbut-2-enyl)-5-(2-methylpropanoyl)benzofuran-4(2H)-one; 8/8a). Structure elucidation was based on extensive 1D and 2D NMR studies, as well as on data derived from mass spectrometry. Furthermore, the cytotoxicity towards KB nasopharyngeal carcinoma cells and the antibacterial activity were determined.

A new cytotoxic 1,7-dioxa-dispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivative, aculeatin D, and a new alkenone, 5-hydroxy-hexacos-1-en-3-one, have been isolated as minor compounds from the rhizomes of Amomum aculeatum. Their structures have been determined mainly by NMR spectroscopy and mass spectrometry. Aculeatin D showed high cytotoxicity against the KB and the L-6 cell line with IC50of 0.38 μg/ml and 1 μg/ml, respectively. Additionally, it revealed remarkable activity against two Plasmodium falciparumstrains, as well as against Trypanosoma brucei rhodesienseand Trypanosoma cruzi. 5-Hydroxy-hexacos-1-en-3-one exhibited neither cytotoxic nor antiprotozoal activity, whereas antibacterial testing against Bacillus cereus, Escherichia coliand Staphylococcus epidermidisshowed moderate to strong activity for both compounds.

Cytotoxicity against the KB cancer cell line as a lead bioactivity-guided fractionation of the petroleum ether extract of rhizomes of Amomum aculeatum Roxb. led to the isolation of three novel dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivatives. The structures of aculeatin A (1), aculeatin B (2), and aculeatin C (3) were established as rel-(2R,4R,6S)- and rel-(2R,4R,6R)-4-hydroxy-2-tridecyl-1,7-dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one (1 and 2, resp.) and rel-(2R,4R,6R)-2-[4-(3-dodecyl-2-heptyl-3-hydroxy-6-oxocylohexa-1,4-dienyl)-2-oxobutyl]-4-hydroxy-1,7-dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one (3) by extensive spectroscopic analyses, particularly ¹³C-NMR, inverse-gated ¹³C, HMQC, HMBC, NOESY, and INADEQUATE NMR experiments as well as mass spectrometry. The aculeatins represent a novel type of natural products. All compounds showed high cytotoxicity against the KB cell line: 1, IC50=1.7 μM; 2, IC50=2.0 μM; 3, IC50=1.6 μM. Additional testing against two Plasmodium falciparum strains as well as against trypomastigote forms of Trypanosoma brucei rhodesiense and Trypanosoma cruzi showed strong activities, particularly against P. falciparum strain K1 (1, IC50=0.18 μM; 2, IC50=0.43 μM; 3, IC50=0.37 μM).

Two dammarane-type saponins with a novel aglycone derived from the parent 16,22-epoxy-24-methylidenedammarane and lotoside A, a new lotogenin derivative, were isolated from the MeOH extract of the stem bark of the Brazilian medicinal plant Zizyphus joazeiro, in addition to the known saponin 3β-{{O-[O-[α-L-arabinofuranosyl-(1→2)]-O-[β-D-glucopyranosyl-(1→3)]]-α-L-arabinopyranosyl}oxy}jujubogenin (1). The structures of the new compounds were determined as 16,22-epoxy-3β-[(β-D-glucopyranosyl)oxy]-24-methylidenedammarane-15α,16α,20β-triol (2), 16,22-epoxy-3β-{{O-[O-[β-D-glucopyranosyl-(1→2)]-O-[β-D-apiofuranosyl-(1→3)]]-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl}oxy}-24-methylidenedammarane-15α,16α,20β-triol (3), and 3β-{{O-[O-[β-D-glucopyranosyl-(1→2)]-O-[β-D-apiofuranosyl-(1→3)]]-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl}oxy}lotogenin (4) by means of 1D- and 2D-NMR spectroscopy, as well as FAB mass spectrometry. For the novel aglycone, we propose the name joazeirogenin and, for the new saponins, joazeiroside A (2) and B (3). Joazeirogenin was found to be 16,22-epoxy-24-methylidenedammarane-3β,15α,16α,20β-tetrol.

One new, namely 6-methoxykaempferol 3-O-[β-apiofuranosyl(1→2)]-β-glucopyranosyl(1→6)-β-glucopyranoside (2), and two known flavonoid glycosides, spinacetin 3-O-[β-apiofuranosyl(1→2)]-β-glucopyranosyl(1→6)-β-glucopyranoside (1)and spinacetin 3-O-gentiobioside (3), were isolated from the roots of Chenopodium bonus-henricusL. Their structures were determined by means of spectroscopic methods (1D, 2D NMR, UV, IR) and HR-ESI-MS. Radical scavenging and anti-oxidant activities of 1and 3were established using DPPH and ABTS free radicals, FRAP assay and inhibition of lipid peroxidation (LP) in a linoleic acid system by the ferric thiocyanate method. Compound 3was found to possess stronger DPPH and ABTS radical scavenging activity (IC500.44 ± 0.008 mM and 0.089 ± 0.002 mM, respectively) compared with 1(IC501.22 ± 0.010 mM and 0.11 ± 0.004 mM, respectively). Both flavonoids inhibited the lipid peroxidation of linoleic acid significantly. Additionally, 1and 3significantly reduced the cellular damage caused by the hepatotoxic agent CCl4in rat hepatocytes and preserved cell viability and GSH level, decreased LDH leakage and reduced lipid damage. Effects were similar to those of the positive control silymarin. Control of self-toxic effects made in a MTT based assay using HepG2 cells revealed statistically significant cytotoxic effects only in very high concentrations (exceeding mM) and an incubation time of 72 h, making flavonoid glycosides with a 6-methoxykaempferol skeleton a promising and safe class of hepatoprotective compounds.

A detailed phytochemical investigation of the dichloromethane extract of the aerial parts of Hypericum maculatumCrantz. led to the isolation of four new (2-5) and six known (1a/b, 6-10) polyprenylated phloroglucinol derivatives. The new compounds were identified by means of spectral methods (MS, NMR, IR, UV) as (E)-4-(3,7-dimethylocta-2,6-dien-1-yl)-5-hydroxy-2-(3-methylbut-2-en-1-yl)-3,6-dioxocyclohexa-1,4-dien-1-yl isobutyrate (2), (E)-2-(3,7-dimethylocta-2,6-dien-1-yl)-5-hydroxy-4-(3-methylbut-2-en-1-yl)-3,6-dioxocyclohexa-1,4-dien-1-yl isobutyrate (3), (E)-4-(3,7-dimethylocta-2,6-dien-1-yl)-5-hydroxy-2-(3-methylbut-2-en-1-yl)-3,6-dioxocyclohexa-1,4-dien-1-yl 2-methylbutanoate (4) and (E)-2-(3,7-dimethylocta-2,6-dien-1-yl)-5-hydroxy-4-(3-methylbut-2-en-1-yl)-3,6-dioxocyclohexa-1,4-dien-1-yl 2-methylbutanoate (5). The known compounds have been identified as hyperpolyphyllirin/hyperibine J (1a/b), erectquione A (6), (E)-1-(3-(3,7-dimethylocta-2,6-dien-1-yl)-2,4,6-trihydroxyphenyl)-2-methylpropan-1-one (7), (E)-1-(3-(3,7-dimethylocta-2,6-dien-1-yl)-2,4,6-trihydroxyphenyl)-2-methylbutan-1-one (8), 1-(5,7-dihydroxy-2-methyl-2-(4-methylpent-3-en-1-yl)chroman-8-yl)-2-methylpropan-1-one (9) and 1-(6,8-dihydroxy-1,1,4a-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-xanthen-5-yl)-2-methylpropan-1-one (10). The stereochemistry of 1ais described for the first time. The cytotoxicity of 1-6on SKW-3, BV-173 and K-562 tumor cell lines was determined using MTT based assays.

Two new glycosides of 30-normedicagenic acid, namely 3-O-[β-D-glucuronopyranosyl methyl ester]-2β,3β-dihydroxy-30-noroleane-12,20(29)-diene-23,28-dioic acid 28-O-β-D-glucopyranosyl ester, and 3-O-β-D-glucopyranosyl-2β,3β-dihydroxy-30-noroleane-12,20(29)-diene-23,28-dioic acid, together with the known 3-O-β-glucopyranosyl-2β,3β-dihydroxy-30-noroleane-12,20(29)-diene-23,28-dioic acid 28-O-β-glucopyranosyl ester, and 3-O-β-glucuronopyranosyl-2β,3β-dihydroxy-30-noroleane-12,20(29)-diene-23,28-dioic acid 28-O-β-glucopyranosyl ester were isolated from the aerial parts of Chenopodium foliosumAsch. The structures of the compounds were determined by means of spectroscopic methods (1D and 2D NMR, UV, IR) and HRMS-ESI. The compounds were tested for cytotoxicity on three leukemic cell lines (BV-173, SKW-3, HL-60). In addition, the saponins showed moderate stimulatory effects on interleukin-2 production in PHA/PMA stimulated Jurkat E6.1 cells.

Thirteen prenylated acylphloroglucinols (1 – 13), including 2 previously undescribed compounds (1) and (2), were isolated from Hypericum jovis. Their structures were elucidated by high-field NMR spectroscopy. The isolated prenylated acylphloroglucinols were evaluated for their anti-inflammatory effects in vitro through the reduction of the intercellular adhesion molecule 1 expression induced by TNF- α in the human microvascular endothelial cells 1 cell line. Compounds 3, 5, 6, 8, and 12 significantly reduced intercellular adhesion molecule 1 expression in a concentration-dependent manner with IC50 values of 16.9, 34.4, 4.0, 3.2, and 7.7 µM, respectively. In addition, compound 12 showed notable inhibitory activity on the formation of cyclooxygenase-1- and 12-lipoxygenase-derived inflammatory mediators in an ex vivo cyclooxygenase-lipoxygenase assay. Eleven further constituents were isolated (14 – 24), including the rare quercetin 3-O-(2-O-acetyl)-arabinofuranoside (18). [ABSTRACT FROM AUTHOR]