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Biomedical subjects

Rudolf Bauer

Publications and source records attributed to Rudolf Bauer.

At least 19 recordsLinked to original sources
PubMed2006

Antimycobacterial activity of geranylated furocoumarins from Tetradium daniellii.

Seven geranylated furocoumarins were isolated from the fruits of TETRADIUM DANIELLII (Benn.) T.G. Hartley (Rutaceae) and tested for their antimycobacterial activity against MYCOBACTERIUM FORTUITUM, M. SMEGMATIS and M. PHLEI. They were shown to be highly active, with minimal inhibitory concentrations (MICs) ranging from 8 to 64 microg/mL. Xanthotoxin and xanthotoxol, representing furocoumarins lacking the lipophilic geranyl side chain, were tested similarly and were shown to be inactive. Geraniol alone was inactive as well. The antimycobacterial activity of the substances was dependent on the position and polarity of the geranyl moiety. The compounds were purified using chromatographic methods. Structure elucidation was achieved with 1D and 2D NMR experiments.

Anti-Bacterial Agents↗
PubMed2006

In vitro 12(S)-HETE and leukotriene metabolism inhibitory activity of sesquiterpenes of Warburgia ugandensis.

Twelve drimane and coloratane sesquiterpenes, isolated from the stem bark of Ethiopian Warburgia ugandensis, were evaluated for inhibition of 12( S)-HETE using human platelets and of leukotriene B (4) formation using activated human neutrophile granulocytes. Among the compounds examined for inhibition of 12-LOX, ugandensidial and muzigadial displayed potent inhibitory activity with IC (50) values of 3.3 and 20.2 microM, respectively, in comparison to the positive control baicalein with an IC (50) value of 20.0 microM. In the 5-LOX assay muzigadial and ugandensidial also exhibited a dose dependent and potent inhibitory effect on LTB (4) biosynthesis with an IC (50) value of 10.2 and 12.7 microM, respectively, compared to the well known 5-LOX inhibitor zileuton with an IC (50) value of 10.4 microM. In contrast, none of the other sesquiterpenoids showed significant inhibition of either 12( S)-HETE or LTB (4) metabolism.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2006

Chamazulene carboxylic acid and matricin: a natural profen and its natural prodrug, identified through similarity to synthetic drug substances.

Chamazulene carboxylic acid (1) is a natural profen with anti-inflammatory activity and a degradation product of proazulenic sesquiterpene lactones, e.g., matricin. Both 1 and proazulenes occur in chamomile (Matricaria recutita), yarrow (Achillea millefolium), and a few other Asteraceae species. It was isolated in improved yields, characterized physicochemically, and found to be an inhibitor of cyclooxygenase-2, but not of cyclooxygenase-1. It had anti-inflammatory activity in several animal models with local and systemic application. When human volunteers were given matricin orally, plasma levels of 1 were found to be in the micromolar range. Matricin was converted to 1 in artificial gastric fluid, but not in artificial intestinal fluid. Matricin and the yarrow proazulenes are proposed to be anti-inflammatory through conversion to 1. Intriguingly, the biological activity of the natural compound 1 was found because of its similarity to fully synthetic drug substances. This is the reverse process of the common lead function of natural compounds in drug discovery.

Achillea↗
PubMed2006

Activity-guided isolation of scopoletin and isoscopoletin, the inhibitory active principles towards CCRF-CEM leukaemia cells and multi-drug resistant CEM/ADR5000 cells, from Artemisia argyi.

The ethyl acetate extract of Artemisia argyi leaves showed substantial inhibition in a cell proliferation assay using human CCRF-CEM leukaemia cells. Bioassay-guided fractionation of the extract led to the isolation of scopoletin and isoscopoletin as the active principles. Their IC50 values were 2.6 and 4.0 microM, respectively. Additionally the two substances were tested against the multidrug resistant subline, CEM/ADR5000 where they both showed IC50 values of 1.6 microM. In contrast to the standard cytostatic drugs doxorubicin, vincristine, and paclitaxel, CEM/ADR5000 cells therefore did not exhibit cross-resistance to scopoletin and isoscopoletin.

Antineoplastic Agents, Phytogenic↗
PubMed2005

An evaluation of Echinacea angustifolia in experimental rhinovirus infections.

BACKGROUND: Echinacea has been widely used as an herbal remedy for the common cold, but efficacy studies have produced conflicting results, and there are a variety of echinacea products on the market with different phytochemical compositions. We evaluated the effect of chemically defined extracts from Echinacea angustifolia roots on rhinovirus infection. METHODS: Three preparations of echinacea, with distinct phytochemical profiles, were produced by extraction from E. angustifolia roots with supercritical carbon dioxide, 60 percent ethanol, or 20 percent ethanol. A total of 437 volunteers were randomly assigned to receive either prophylaxis (beginning seven days before the virus challenge) or treatment (beginning at the time of the challenge) either with one of these preparations or with placebo. The results for 399 volunteers who were challenged with rhinovirus type 39 and observed in a sequestered setting for five days were included in the data analysis. RESULTS: There were no statistically significant effects of the three echinacea extracts on rates of infection or severity of symptoms. Similarly, there were no significant effects of treatment on the volume of nasal secretions, on polymorphonuclear leukocyte or interleukin-8 concentrations in nasal-lavage specimens, or on quantitative-virus titer. CONCLUSIONS: The results of this study indicate that extracts of E. angustifolia root, either alone or in combination, do not have clinically significant effects on infection with a rhinovirus or on the clinical illness that results from it.

Adult↗
PubMed2005

Molecular modes of action of cantharidin in tumor cells.

Cancer chemotherapy is often limited by patient's toxicity and tumor drug resistance indicating that new drug development and modification of existing drugs is critical for improving the therapeutic response. Traditional Chinese medicine is a rich source of potential anticancer agents. In particular, cantharidin (CAN), the active principle ingredient from the blister beetle, Mylabris, has anti-tumor activity, but the cytotoxic mechanism is unknown. In leukemia cells, cantharidin induces apoptosis by a p53-dependent mechanism. Cantharidin causes both DNA single- and double-strand breaks. Colony-forming assays with knockout and transfectant cells lines showed that DNA polymerase beta, but not ERCC1, conferred increased cell survival after cantharidin treatment, indicating that base excision repair (BER), rather than nucleotide excision repair (NER), is important for CAN-induced DNA lesions. Oxidative stress-resistant thymic lymphoma-derived WEHI7.2 variants are also more resistant to cantharidin. These data suggest that cantharidin treatment causes oxidative stress that provokes DNA damage and p53-dependent apoptosis.

Antineoplastic Agents↗
PubMed2005

Marine polyprenylated hydroquinones, quinones, and chromenols with inhibitory effects on leukotriene formation.

A series of polyprenylated hydroquinones, quinones, and chromenols were isolated from the extracts of the marine sponge Ircinia spinosula and the brown alga Taonia atomaria, which gave rise to the constituents 1-4 and 5-8, respectively. Compounds 1, 2, 6, and 7 are new natural products, which were fully characterized. Their anti-inflammatory activities in terms of leukotriene formation were evaluated in an in vitro assay with pork leukocytes. The new hydroxylated compound, 2'-[28-hydroxy]heptaprenyl-1',4'-hydroquinone (= 2-[(2E,6E,10E,14E,18Z,22E)-19-(hydroxymethyl)-3,7,11,15,23,27-hexamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl]benzene-1,4-diol; 1), the known tetraprenyl benzoquinone sargaquinone (5), and the known polyprenyl chromenols 3 and 4 exhibited the highest anti-inflammatory activities, with IC50 values of 1.9-9.4 microM (Table 3). Potential structure-activity relationships (SAR) are discussed.

Animals↗
PubMed2005

Is surgical closure of patent foramen ovale the gold standard for treating interatrial shunts? An echocardiographic follow-up study.

BACKGROUND: Surgical closure of patent foramen ovale (PFO) has been considered definitive and the gold standard for preventing recurrent paradoxical embolism. However, in contrast to transcatheter PFO closure, patients undergoing operation have not systematically been re-evaluated for residual shunting. This study aimed to assess the efficacy of surgical PFO closure during follow-up by transesophageal echocardiography (TEE). METHODS: Eleven adult patients with diagnosis of a PFO by contrast and/or color Doppler TEE underwent PFO closure by thoracotomy and direct suturing because of paradoxical embolism (n = 4), because of impending paradoxical embolism (n = 1), or during valve operation (n = 6). RESULTS: TEE performed 5 days to 7 months after PFO closure revealed residual shunting in 8 of 11 patients (73%). The shunt size was unchanged in two patients. According to the color Doppler jet width across the atrial septum, the postoperative PFO diameter was smaller in 5 of the remaining 6 patients. Right-to-left shunting by contrast TEE, however, had newly developed (n = 1) or increased (n = 2) for patients with concomitant valve operation. Despite therapeutic anticoagulation a cerebrovascular event occurred in one patient 4 weeks after attempted PFO closure. The mechanism for persistent shunting was incomplete sealing of septum primum and septum secundum by the suture line (n = 6) or a new iatrogenic defect of the fossa ovalis caused by surgical manipulation (n = 2). In two patients a second TEE after 12 and 41 months revealed enlargement of the PFO diameter. CONCLUSIONS: Surgical PFO closure can not be regarded as the gold standard for definitive treatment of interatrial shunts. Residual shunting present in a high proportion of patients may partly explain the recurrence of embolic events.

Adult↗
PubMed2005

Synthesis and biological evaluation of a new class of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.

A series of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential human 5-LOX and COX 1 and COX-2 inhibitors structurally related to the 1-phenyl-3-pyrazolidinone (phenidone, 1) have been synthesized and the activity against COX-1, COX-2 and human 5-LOX enzymes has been evaluated. All the derivatives showed poor activity against enzymes. These data, together with our previous studies, indicated that phenidone and related compounds are not suitable as human 5-LOX inhibitors and that pyrazoline nucleus should not be considered a good scaffold for inhibitors of human 5-LOX enzyme, suggesting the necessity to revisit the proposed mechanism of action of phenidone (1) in human models.

Animals↗
PubMed2005

Flavonolignans from Avena sativa.

Three flavonolignans derived from the flavone tricin were isolated from Avena sativa herb. This is the first report of the presence of flavonolignans in A. sativa. In the known compounds 1a and 1b, a coniferyl alcohol moiety is linked to the flavone by an ether bond; in the new natural product 2, it is linked by C-C bonds. Structure elucidation of compound 2 was performed by 1D and 2D NMR experiments, and the absolute configuration was determined from circular dichroic data.

Austria↗
PubMed2005

Inhibition of leukotriene biosynthesis by stilbenoids from Stemona species.

Fifteen stilbenoids and two alkaloids from Stemona collinsae, S. tuberosa, and S. peirrei were tested alongside the commercially available stilbenoids resveratrol and pinosylvin for inhibition of leukotriene formation in an ex vivo test system based on activated human neutrophilic granulocytes. The stilbenoids resveratrol (1), pinosylvin (2), dihydropinosylvin (3), stilbostemin A (4), stilbostemin B (5), stilbostemin D (6), stilbostemin F (7), stilbostemin G (8), stemofuran B (9), stemofuran C (10), stemofuran D (11), stemofuran G (12), stemofuran J (13), stemanthrene A (14), stemanthrene B (15), stemanthrene C (16), and stemanthrene D (17) showed structure-dependent activities with IC(50) values ranging from 3.7 to >50 microM. The alkaloids tuberostemonine (18) and neotuberostemonine (19) were inactive at a concentration of 50 microM.

Alkaloids↗
PubMed2005

Discovering COX-inhibiting constituents of Morus root bark: activity-guided versus computer-aided methods.

The aim of this study was to compare the efficiency of two well known approaches for the discovery of the bioactive principle/s in medicinal plants, namely the activity-guided isolation versus the computer-aided drug discovery by means of virtual screening (VS) techniques. Morus root bark of Morus sp. L. (Moraceae) was selected as application example for the discovery of compounds with anti-inflammatory activity. The two cyclooxygenase isoenzymes COX-1 and COX-2 were chosen as targets and the corresponding pharmacophore models were generated by our research. The activity-guided fractionation of the methanol extract of the root bark resulted in the isolation of nine compounds. Their structures were elucidated by mass spectrometry, 1- and 2-dimensional NMR experiments and identified as moracins B, M, the regioisomers O/P as a mixture, and sanggenons B, C, D, E and O. The COX-1 and COX-2 inhibiting activities of these compounds were established in an enzyme assay and compared with the predicted hits obtained from the VS. Sanggenons C, E, and O, that were tested the first time for an inhibitory effect on COX-1 and -2, showed IC50 values of 10-14 microM, and 40-50 microM, respectively. The results show that the COX activities obtained for the sanggenons are correctly predicted by the in silico filtering experiment. In the case of the isolated moracins, however, it failed because the COX inhibiting activities of moracins M and P/O were not retrieved by the VS. Structure-activity relationships of the isolated compounds are discussed as well as potential pitfalls and advantages of the applied strategies.

Cyclooxygenase 1↗
PubMed2005

The endocannabinoid system as a target for alkamides from Echinacea angustifolia roots.

Alkamides are the major lipophilic constituents of Echinacea angustifolia roots. Due to their structural similarity with anandamide, we have evaluated their ability to bind to rodent cannabinoid receptors CB1 and CB2 by a standard receptor binding assay using [(3)H]CP-55,940 as a radioligand. The alkamides exhibited selective affinity especially to CB2 receptors and can therefore be considered as CB ligands. Most of the alkamides showed good metabolic stability as indicated by the similarity between affinity to CB1 determined in the presence/absence of the protease inhibitor PMSF. It is suggested that CB2 interactions may be the molecular mode of action of Echinacea alkamides as immunomodulators.

Animals↗
PubMed2005

Bioavailability and pharmacokinetics of alkamides from the roots of Echinacea angustifolia in humans.

Alkamides are suspected to contribute to the activity of Echinacea preparations. They are mainly derived from undeca- and dodecanoic acid and differ in the degree of unsaturation and the configuration of the double bonds. In total, 6 alkamides have been isolated from the roots of Echinacea angustifolia as major lipophilic constituents and have been investigated regarding their pharmacokinetics. A sensitive and specific method has been developed for the identification and quantification of these alkamides in human plasma using liquid chromatography electrospray ionization ion-trap mass spectrometry. The method was applied to analyze plasma samples obtained from a randomized, open, single-dose, crossover study after oral administration of a 60% ethanolic extract from the roots of E. angustifolia to 11 healthy subjects. The maximum concentration of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, the main alkamides in the roots of E. angustifolia, appeared already after 30 minutes and was 10.88 ng/mL for the 2.5-mL dose.

Administration, Oral↗
PubMed2004

Synthesis and biological evaluation of new phenidone analogues as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.

A new series of potential human 5-LOX inhibitors structurally related to the 1-phenyl-3-pyrazolidinone (phenidone, 2) has been synthesized and the activity against COX-1, COX-2, and human 5-LOX enzymes has been evaluated. In contrast with literature data, we observed that phenidone resulted to be inactive against human 5-LOX, while retains its activity against cyclooxygenases in a micromolar range. The present results suggest that the substitution of the amino function at the 4-position is detrimental in terms of activity toward COX-1 and COX-2, while the presence of a double bond at the 4,5-position does not alter the biological profile against COX. The absence of activity vs. human 5-LOX strongly suggests a re-consideration of phenidone and its analogs as 5-LOX inhibitors in humans.

Cyclooxygenase Inhibitors↗
PubMed2004

Inhibition of leukotriene biosynthesis by quinolone alkaloids from the fruits of Evodia rutaecarpa.

The n-hexane extract of the fruits of Evodia rutaecarpa showed a considerable inhibiting effect on leukotriene biosynthesis in human granulocytes. Bioassay-guided fractionation of the extract led to the isolation of the 5 quinolone alkaloids: 1-methyl-2-nonyl-4(1H)-quinolinone, 1-methyl-2-(6Z)-6-undecenyl-4(1H)-quinolinone, 1-methyl-2-(4Z,7Z)-4,7-tridecadienyl-4(1H)-quinolinone, evocarpine and 1-methyl-2-(6Z,9Z)-6,9-pentadecadienyl-4(1H)-quinolinone. The compounds exhibited inhibitory activity on leukotriene biosynthesis in a bioassay using human polymorphonuclear granulocytes, with IC50 values of 12.1, 10.0, 10.1, 14,6 and 12.3 microM, respectively. Structure elucidation of the compounds was achieved by 1D and 2D NMR experiments and comparison of spectral data with literature data.

Evodia↗