K. Seifert - Academia.edu (original) (raw)

Papers by K. Seifert

Planta medica, 1989

From the roots of VERBASCUM PULVERULENTUM Vill. two iridoids of the 6- O-alpha- L-rhamnopyranosyl... more From the roots of VERBASCUM PULVERULENTUM Vill. two iridoids of the 6- O-alpha- L-rhamnopyranosylcatalpol-type have been isolated and structural elucidated.

Die Pharmazie, 2001

The influence of the triterpenoid saponins 1-10 has been investigated on murine spleenocytes in t... more The influence of the triterpenoid saponins 1-10 has been investigated on murine spleenocytes in the lymphocyte transformation test and on murine macrophages in an phagocytosis assay. The lymphocyte transformation test and the phagocytosis assay showed that the tested compounds have no stimulating effect. However, a significant inhibition of lymphocyte proliferation by the triterpenoid saponins 2, 6 and 10 was demonstrated.

Respiratory Medicine, 2000

Phytochemistry, 1999

Two new triterpenoid saponins, 3-O-{[b-D-glucopyranosyl-(1 4 2)]-[a-L-arabinopyranosyl-(1 4 3)]-a... more Two new triterpenoid saponins, 3-O-{[b-D-glucopyranosyl-(1 4 2)]-[a-L-arabinopyranosyl-(1 4 3)]-a-L-arabinopyranosyl}ursolic acid-28-O-[b-D-glucopyranosyl] ester (indicasaponin A), 3-O-{[b-D-glucopyranosyl-(1 4 2)]-[a-L-arabinopyranosyl-(1 4 3)]a-L-arabinopyranosyl}-oleanolic acid-28-O-[b-D-glucopyranosyl] ester (indicasaponin B) and two known triterpenoid saponins, 3-O-[b-D-glucopyranosyl-(1 4 3)-a-L-arabinopyranosyl]-ursolic acid-28-O-[b-D-glucopyranosyl] ester, 3-O-[b-D-glucopyranosyl-(1 4 3)-a-L-arabinopyranosyl]-oleanolic acid-28-O-[b-D-glucopyranosyl] ester have been isolated from Fagonia indica. The structures were determined primarily by NMR spectroscopy. The assignment of NMR signals was performed by means of 1 H± 1 H COSY, NOESY, ROESY, TOCSY, HMQC and HMBC experiments. #

Persoonia - Molecular Phylogeny and Evolution of Fungi, 2012

New Phytologist, 2006

Since the 1970s it has been known that the nursery pollinator Hadena bicruris is attracted to the... more Since the 1970s it has been known that the nursery pollinator Hadena bicruris is attracted to the flowers of its most important host plant, Silene latifolia , by their scent. Here we identified important compounds for attraction of this noctuid moth. • Gas chromatographic and electroantennographic methods were used to detect compounds eliciting signals in the antennae of the moth. Electrophysiologically active compounds were tested in wind-tunnel bioassays to foraging naïve moths, and the attractivity of these compounds was compared with that to the natural scent of whole S. latifolia flowers.

Neuroscience, 1995

We investigated the effects of intracerebroventricular injection of angiotensin II on neuronal im... more We investigated the effects of intracerebroventricular injection of angiotensin II on neuronal immediate early gene-encoded protein synthesis in the brain of conscious rats. The expression of seven immediate early gene-encoded transcription factors FosB, JunB, JunD, and Krox-24 (NGFI-A, Egr-1, Zif/268) was assessed simultaneously. Angi0tensin II (1, 10, 100 ng) induced a dose-dependent expression of c-Fos and Krox-24 in the subfornical organ, the median preoptic area and in the paraventricular nucleus and supraoptic nucleus of the hypothalamus, regions known to be involved in the central osmoregulatory and neuroendocrine actions of angiotensin II. FosB expression was induced four hours after icv injection of the highest dose of angiotensin II in the median preoptic area and paraventricular nucleus; c-Jun expression was restricted to the median preoptic area, subfornical organ and paraventricular nucleus, and JunB was only induced in the median preoptic area and subfornical organ. In these above mentioned regions, JunD exhibited a high basal staining, which was not visibly altered by angiotensin II. Krox-20 was not induced by angiotensin II. Intracerebroventricular injections of isotonic saline did not induce immediate early gene expression in any of the above brain areas. The angiotensin II-AT1 receptor antagonist, losartan, applied intracerebroventricular five minutes prior to angiotensin II, prevented the angiotensin II-induced immediate early gene protein expression. Losartan alone had no effects on immediate early gene expression.

Biological Mass Spectrometry, 1981

The fragmentation behaviour of N-6 substituted ergoline derivatives (acylaminothiocarbonyl, thiaz... more The fragmentation behaviour of N-6 substituted ergoline derivatives (acylaminothiocarbonyl, thiazolyl) has been studied using electron impact, field desorption and collisional activation mass spectrometry. The specific fragmentations are compared with structurally related compounds (piperidine and piperidine-3-carboxylic acid methyl ester derivatives).

Helvetica Chimica Acta, 1992

Introduction. Ergot is a drug known to mankind for centuries, and some ergot derivatives such as ... more Introduction. Ergot is a drug known to mankind for centuries, and some ergot derivatives such as ergotamine, 9,10-dihydroergotamine, and 2-bromo-a -ergocryptine are presently used as therapeutic agents. The search continues for more active and especially more specifically ...

Drug Resistance Updates, 2006

Miltefosine (hexadecylphosphocholine, MIL), registered as Impavido ® , has become the first oral ... more Miltefosine (hexadecylphosphocholine, MIL), registered as Impavido ® , has become the first oral drug for the treatment of visceral and cutaneous leishmanasis. MIL is a simple molecule, very stable, relatively safe and highly efficient in clinical trials. However, MIL requires a long treatment course (28 days) and has a long half-life (around 150 h), which might accelerate the emergence of drug resistance in case of inadequate use. The mechanisms of MIL resistance have been studied in vitro with experimental resistant lines. Resistance was shown to develop quickly in Leishmania promastigotes. Interestingly, a decreased MIL accumulation has always accounted for the resistance phenotype. The lower MIL accumulation can be achieved by two independent mechanisms: (i) an increase in drug efflux, mediated by the overexpression of the ABC transporter P-glycoprotein, and (ii) a decrease in drug uptake, which is easily achieved by the inactivation of any one of the two proteins known to be responsible for the MIL uptake, the MIL transporter LdMT and its beta subunit LdRos3. Policies concerning a proper use of this drug should be followed and supervised by health authorities of endemic areas to minimalize the risk for the appearance of drug failures and to ensure a long life span for this effective oral drug.

Archives of Medical Research, 2000

Antimicrobial Agents and Chemotherapy, 2014

Many of the nitroaromatic agents used in medicine function as prodrugs and must undergo activatio... more Many of the nitroaromatic agents used in medicine function as prodrugs and must undergo activation before exerting their toxic effects. In most cases, this is catalyzed by flavin mononucleotide (FMN)-dependent type I nitroreductases (NTRs), a class of enzyme absent from higher eukaryotes but expressed by bacteria and several eukaryotic microbes, including trypanosomes and Leishmania. Here, we utilize this difference to evaluate whether members of a library of aziridinyl nitrobenzamides have activity against Leishmania major. Biochemical screens using purified L. major NTR (LmNTR) revealed that compounds containing an aziridinyl-2,4-dinitrobenzyl core were effective substrates for the enzyme and showed that the 4-nitro group was important for this activity. To facilitate drug screening against intracellular amastigote parasites, we generated leishmanial cells that expressed the luciferase reporter gene and optimized a mammalian infection model in a 96-well plate format. A subset of aziridinyl-2,4-dinitrobenzyl compounds possessing a 5-amide substituent displayed significant growth-inhibitory properties against the parasite, with the most potent agents generating 50% inhibitory concentrations of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;100 nM for the intracellular form. This antimicrobial activity was shown to be LmNTR specific since L. major NTR(+/-) heterozygote parasites were slightly resistance to most aziridinyl dinitrobenzyl agents tested. When the most potent leishmanicidal agents were screened against the mammalian cells in which the amastigote parasites were propagated, no growth-inhibitory effect was observed at concentrations of up to 100 μM. We conclude that the aziridinyl nitrobenzamides represent a new lead structure that may have the potential to treat leishmanial infections.

Antimicrobial Agents and Chemotherapy, 2001

The protozoan parasite Entamoeba histolytica is the cause of amoebic dysentery and liver abscess.... more The protozoan parasite Entamoeba histolytica is the cause of amoebic dysentery and liver abscess. It is therefore responsible for significant morbidity and mortality in a number of countries. Infections with E. histolytica are treated with nitroimidazoles, primarily with metronidazole. At this time, there is a lack of useful alternative classes of substances for the treatment of invasive amoebiasis. Alkylphosphocholines (alkyl-PCs) such as hexadecyl-PC (miltefosine) were originally developed as antitumor agents, but recently they have been successfully used for the treatment of visceral leishmaniasis in humans. We examined hexadecyl-PC and several other alkyl-PCs with longer alkyl chains, with and without double bond(s), for their activity against two strains of E. histolytica. The compounds with the highest activity were oleyl-PC, octadecyl-PC, and nonadecenyl-PC, with 50% effective concentrations for 48 h of treatment between 15 and 21 M for strain SFL-3 and between 73 and 98 M for strain HM-1:IMSS. We also tested liposomal formulations of these alkyl-PCs and miltefosine. The alkyl-PC liposomes showed slightly lower activity, but are expected to be well tolerated. Liposomal formulations of oleyl-PC or closely related alkyl-PCs could be promising candidates for testing as broadspectrum antiprotozoal and antitumor agents in humans.

Acta Pharmaceutica, 2000

Some new hydrazono 5a,b, thiosemicarbazono 6a-c, and oximo chromenes 7a-c were prepared via the r... more Some new hydrazono 5a,b, thiosemicarbazono 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding beta-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory and ulcerogenic score activities compared to indomethacin.

Proceedings of the …, 1993

Basement at ODP Hole 900A consists of metamorphosed cumulate gabbros with discontinuous foliation... more Basement at ODP Hole 900A consists of metamorphosed cumulate gabbros with discontinuous foliation bands of recrystallized plagioclase and clinopyroxene containing a few large isolated porphyroclasts of strained plagioclase and clinopyroxene ...