PubMed Health⌕ Search

Biomedical subjects

P Potier

Publications and source records attributed to P Potier.

At least 55 records · Page 3Linked to original sources
PubMed1993

NO, thiols and disulfides.

The chemical nature of the messenger molecule, nitric oxide (NO), and especially its reactivity towards thiol groups and disulfides, could explain, at least partly, its intervention in so many different biological processes. NO can be regarded as the smallest molecule suitable for electron transport in biological systems. The S-nitrosation reaction and its reverse reaction represent the most convenient general way to store, to transport and finally to release NO. Nitric oxide is also particularly convenient for playing a role in interconversions of thiol groups and disulfides in chain radical or oxidation-reduction processes, and to be subsequently engaged in complex sequences of reactions accounting for different biological situations.

Animals↗
PubMed1993

Structure-activity relationships of Taxol and Taxotere analogues.

From Taxol, Taxotere, and 10-deacetyl baccatin III, a number of compounds have been prepared. Their biological activity was evaluated on microtubule disassembly at 0 degrees C. The conformation of these Taxol and Taxotere analogues was determined by molecular modeling experiments and nuclear magnetic resonance spectroscopy and compared with the structure of Taxotere in the crystal, obtained by an x-ray analysis. The results of these studies given information on the crucial parts of the active molecules involved in the binding to tubulin.

Antineoplastic Agents, Phytogenic↗
PubMed1993

In vitro biological activities of arglabin, a sesquiterpene lactone from the Chinese herb Artemisia myriantha Wall. (Asteraceae).

The immunomodulating properties of arglabin, a sesquiterpene lactone isolated from Artemisia myriantha Wall. (Asteraceae) were investigated using the murine macrophage tumor line J774.1. Arglabin-stimulated macrophages displayed a strong cytotoxic activity and the lowest doses (1.25 micrograms/mL and 0.125 micrograms/mL) induced a significant stimulation of cell mitochondrial metabolism, which correlated with [3H]TdR uptake by J774.1 cells under the same experimental conditions. In addition, the secretion of cytokines involved in host defence mechanisms--IL-1, TNF-alpha, and IL-2--was investigated upon incubation of J774-1 cells with arglabin. Arglabin triggered the production of the three cytokines from J774-1 cells. However, the pattern of cytokine secretion differed to some extent, according to the methodology used for cytokine measurement: either traditional bioassay or specific immunoassay (ELISA). Our data emphasize a possible proliferative effect of arglabin in the traditional bioassays, at least for the highest concentrations used. The results were verified with specific ELISA immunoassays. Using either method, lower concentrations of arglabin (ranging from 12.5 micrograms/mL to 0.125 micrograms/mL) were the most effective in inducing IL-1, TNF-alpha, or IL-2 secretion. In addition, preliminary data on phagocytosis showed that arglabin enhanced the uptake of fluorescent latex beads by J774.1 cells.

Animals↗
PubMed1992

Alkaloids from Psychotria oleoides with activity on growth hormone release.

Bioactivity-guided purification of a crude alkaloid extract of Psychotria oleoides has afforded a new alkaloid, psycholeine [1], together with quadrigemine C [2], a tetrameric pyrrolidinoindoline compound of unknown stereochemistry. A comparison study of nmr and cd spectra of quadrigemine C and hodgkinsine [3], a trimeric pyrrolidinoindoline substance, led us to suggest the stereochemistry of quadrigemine C. The structure and configuration of psycholeine was determined by spectroscopic means and chemical correlation with quadrigemine C. Psycholeine interacts with somatostatin receptors and exhibits a somatostatin antagonistic activity on GH secretion by pituitary cells in primary culture.

Alkaloids↗
PubMed1992

Scalarane-type bishomosester terpenes from the sponge Phyllospongia foliascens.

Five new 20,24-bishomoscalarane sesterterpenes, phyllactones A [1], B [2], C [3], D [4], and E [5], are reported from the sponge Phyllospongia foliascens collected in the waters of the Nansha Islands in the South China Sea. Structural elucidation of these compounds is based on spectral data and chemical conversions. Phyllactones A and B show moderate cytotoxicity against KB cells (IC50 20 micrograms/ml).

Acetylation↗
PubMed1992

[Anticancer substances of vegetable origin. Spindle poisons: vincaleukoblastine, leurocristine and navelbine; taxol and taxotere].

The biological activity of spindle poisons can easily be measured using an in vitro assay based on the interaction of these substances with their cellular "receptor": tubulin. The use of this assay led us to select Navelbine and Taxotere as antimitotic substances. These compounds, as well as their natural parents: vincaleucoblastine, leurocristine and taxol respectively, have been obtained by semi-synthesis using relatively abundant natural precursors as starting materials. This paper summarizes the preparation of these important anticancer drugs.

Antineoplastic Agents↗
PubMed1991

Relationships between the structure of taxol analogues and their antimitotic activity.

A variety of synthetic analogues of taxol, a naturally occurring antitumor diterpene, were examined for their potency to inhibit microtubule disassembly. For some of the compounds, the in vitro cytotoxic properties showed a good correlation with the tubulin assay. This structure-activity relationship study shows that inhibition of microtubule disassembly is quite sensitive to the configuration at C-2' and C-3'. A correlation between the conformation of the side chain at C-13 and the activity is suggested. Of all the compounds examined, one of the most potent in inhibiting microtubule disassembly and in inhibiting murine P388 leukemic cells, N-debenzoyl-N-tert-(butoxycarbonyl)-10-deacetyltaxol, named taxotere, was selected for evaluation as a potential anticancer agent.

Alkaloids↗
PubMed1990

Synthesis and activity of NAcSerAspLysPro analogues on cellular interactions between T-cell and erythrocytes in rosette formation.

Analogues of NAcSerAspLysPro (AcSDKP), a natural regulator of hematopoiesis isolated from fetal calf bone marrow, were synthesized. The biological activity of these molecules were evaluated in vitro in the rosette assay, which measures the interaction between human Jurkat T-cells and sheep red blood cells. In this test, the tripeptide SerAspLys was the most efficient. Inhibitory activity was detected at the concentration 10(-14) M for the analogue and at 10(-9) M for the parent tetrapeptide. The dipeptide NAcSerAsp still showed activity but at much higher doses (10(-6) M). Substitution of polar amino acids led mostly to inactive molecules. Thus, replacement of Ser by Ala, or Lys by Orn yielded completely inactive compounds and replacement of Asp by Glu decreased the activity (10(-6) M). The present study gives an insight into the role of individual amino acids of AcSDKP in the inhibition of the rosette formation which implicates interactions with T-cell CD2 glycoprotein.

Amino Acid Sequence↗
PubMed1990

Study of the mode of action of some nitrodiphenyl ethers.

Nitrosoderivatives of the nitrodiphenyl ether herbicides (nitrofen, bifenox) have been studied. UV irradiation in different organic solvents gives degradation products. In buffered aqueous media, in the presence of chloroplasts and spin traps such as DMPO, hydroxy and peroxy radicals have been characterized. In organic media and in the presence of spin traps such as DMPO, PBN, 4-POBN, solvent radicals (.CHCl2, .CCl3, .CH2 [symbol: see text]) have been formed. Nitro-derivatives have been studied under UV irradiation and in the presence of tetramethylethylene (TME), alkenylhydroxylamines are formed which autoxidize in nitroxide radicals. The formation of the stable nitroxide radical occurs in the dark process after continuous irradiation. The intensity of the signal decreases strongly when a new irradiation is applied. Radical species, with analogous ESR spectral characteristics are formed on reaction with nitrodiphenyl ethers and fatty acids. The reactivity of these herbicides in micellar media (SDS, Brij 35, and CTAB) has been investigated. The kinetics of formation of the ESR signal corresponding to the photoreduction of the nitrodiphenyl ether in the presence of TME behave differently in a micellar environment as compared to solution. The intensity of the formation of the nitroxide increases under irradiation and decreases in the dark; the rotational correlation time tau c has been determined for each type of micelle. Synthetic nitrosodiphenyl ether made by the reduction of nitrodiphenyl ether using hydrogen gas and PtO2 as a catalyst gives the corresponding amine, which is oxidized with meta-chloroperbenzoic acid (m.CPBA). The nitrosodiphenyl ether in the presence of soja azolectin liposome containing a fluorescent probe has been analysed.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗
PubMed1989

First use of a beta-carboline as photoaffinity label for the benzodiazepine receptor.

Photolabelling of benzodiazepine receptors isolated from rat cortex with a new beta-carboline-type photoaffinity label, ethyl 6-azido-beta-carboline-3-carboxylase, at 254 nm produced a 42% decrease in the maximal number of propyl beta-carboline-3-carboxylate binding sites but practically no decrease in the number of flunitrazepam binding sites. Moreover, the binding affinity of ethyl beta-carboline-3-carboxylase was diminished 11-fold by photolabelling while that of diazepam was diminished less than 2-fold. These results provide additional evidence that beta-carbolines and benzodiazepines bind to discrete sites on the benzodiazepine receptor.

Affinity Labels↗
PubMed1989

Hybrid molecules: growth inhibition of Leishmania donovani promastigotes by thiosemicarbazones of 3-carboxy-beta-carbolines.

The thiosemicarbazones of beta-carboline-3-carboxaldehyde (compound 2) and 3-acetyl-beta-carboline (compound 3) were found to effectively inhibit the in vitro growth of the promastigote form of Leishmania donovani, 50% inhibition being obtained at concentrations of 5.0 and 2.5 microM, respectively, while irreversible growth inhibition was achieved at 40 (compound 2) and 17.5 microM (compound 3). The thiosemicarbazone of pyridine-2-carboxyaldehyde (compound 4) was considerably less active while both methyl beta-carboline-3-carboxylate (compound 1) and the thiosemicarbazone of ethyl 5-formyl-6-azaindole-2-carboxylate (compound 5) were inactive at the highest concentrations tested. At concentrations provoking approximately 50% growth inhibition of promastigotes, compound 2 was observed to preferentially block DNA rather than RNA synthesis, but for compound 3, the reverse was true. Compound 3, the most active analogue studied, may thus act, at least partially, via a novel, though as yet unelucidated, mechanism.

Animals↗
PubMed1989

Synthesis and benzodiazepine receptor affinities of rigid analogues of 3-carboxy-beta-carbolines: demonstration that the benzodiazepine receptor recognizes preferentially the s-cis conformation of the 3-carboxy group.

1H-Indolo[3',2':4,5]pyrido[3,2-b]-2-penten-5-olide (6) and 1H,5H-indolo[3',2'-c]-6,7-dihydro-2-pyridone (7), rigid analogues of methyl 4-ethyl-beta-carboline-3-carboxylate (8) and N-methyl-4-ethyl-beta-carboline-3-carboxamide (9), respectively, were synthesized and their in vitro binding affinities to the central type benzodiazepine receptors were compared. The IC50 values of 6 and 8 were approximately equivalent (42 and 27 nM, respectively). The amide derivative 9, for which theoretical energy calculations indicate that the s-trans carbonyl conformation is the preferred one, displayed very low affinity (IC50 greater than 10(4) nM). However, when the carbonyl group of 9 was forced to adopt the s-cis conformation as in lactam 7, binding to the benzodiazepine receptor was largely restored (IC50 = 150 nM), indicating that the s-cis carboxy conformation at C-3 of beta-carbolines is preferentially recognized by this receptor. In vivo, compound 6 showed neither convulsant, proconvulsant, nor anticonvulsant activity in mice. Moreover, 6 did not antagonize methyl beta-carboline-3-carboxylate induced convulsions in mice. This lack of activity of 6 was attributed to its inability to cross the blood-brain barrier since no significant displacement of [3H]Ro 15-1788 from mouse brain benzodiazepine receptors by 6 could be observed in vivo.

Animals↗
PubMed1988

N-acylated pentapeptides antagonists of substance P on guinea-pig ileum.

Pentapeptides X-D.Trp-Phe-D.Trp-Leu-Y-NH2 (X = H, Boc, parahydroxyphenylacetyl, Y = Met,Leu,Nle,Phe) were tested as antagonists against Substance P and against a specific agonist of the muscular receptor of neurokinins on the guinea-pig ileum. Weak antagonist or agonist activities could be observed with the free or the Boc-protected pentapeptides whilst the acylated compounds could be compared favorably with the best antagonists already described.

Acylation↗
PubMed1988

Hispidulin, a natural flavone, inhibits human platelet aggregation by increasing cAMP levels.

Hispidulin, a natural flavone, and theophylline inhibited platelet aggregation triggered by adenosine-5'-monophosphate, arachidonic acid, paf-acether and collagen. Hispidulin was 100-fold more potent than theophylline. A threshold concentration of PGE1 did not modify the anti-aggregatory effect of hispidulin but potentiated the effect of theophylline. A threshold concentration of hispidulin had no effect on the inhibitory action of theophylline. Hispidulin (100 microM) and theophylline (10 mM) increased the control cAMP level in platelets 4-fold. A threshold concentration of PGE1 had a small effect on hispidulin-induced cAMP levels but increased the theophylline-induced cAMP levels 3-fold. Theophylline (10 mM)-induced cAMP levels were not modified by hispidulin. We demonstrate a correlation between the inhibition of platelet aggregation and the increase in cAMP levels induced by hispidulin. These data suggest that hispidulin could inhibit platelet aggregation by elevating cAMP levels by a mechanism different from that of theophylline or PGE1.

Alprostadil↗
PubMed1987

Isolation and characterization of 9-hydroxy-10-trans,12-cis-octadecadienoic acid, a novel regulator of platelet adenylate cyclase from Glechoma hederacea L. Labiatae.

We have identified and characterized a fatty acid, (9S,10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (9-HODE) as a regulator of adenylate cyclase activity of human platelet membranes. This fatty acid was isolated from a methanolic extract of the plant Glechoma hederacea L. Labiatae (commonly known as 'lierre terrestre', 'ground ivy' or 'creeping Charlie'; it was identified by nuclear magnetic resonance and mass spectroscopy. This compound increased basal adenylate cyclase activity in platelet membranes about threefold and had an EC50 of 10-20 microM. This increase in adenylate cyclase activity occurred without a temporal lag, was reversible, and represented an increase in Vmax without a substantial change in Km for ATP, Mg2+ or Mn2+. In addition, 9-HODE additively or synergistically increased platelet adenylate cyclase activity in response to guanosine 5'-[beta,gamma-imido]triphosphate and forskolin, but the fatty acid failed to alter inhibition of adenylate cyclase activity mediated by epinephrine (alpha 2-adrenergic receptor). Studies of the interaction of 9-HODE with activation of platelet adenylate cyclase activity mediated by prostaglandin E1 (PGE1) and prostaglandin D2 (PGD2) indicated that this fatty acid produced a parallel shift in the concentration/response curve of PGE1 and PGD2 without altering maximal response, which was substantially greater than that observed with 9-HODE alone. From these results, we conclude that 9-HODE appears to be a partial agonist at PGE1 and PGD2 receptors on human platelets. We believe that this is a novel example of a plant-derived fatty acid which acts on cells to regulate adenylate cyclase via prostaglandin receptors.

Adenylyl Cyclases↗
PubMed1987

Synthesis of beta-carboline-benzodiazepine hybrid molecules: use of the known structural requirements for benzodiazepine and beta-carboline binding in designing a novel, high-affinity ligand for the benzodiazepine receptor.

Hybrid molecules incorporating pharmacologically important structural features of both 3-carboxy-beta-carbolines and 1,4-benzodiazepines were synthesized, and their affinities for the benzodiazepine receptor were determined in vitro. One of these hybrids, 8,14-dioxo-13,14-dihydro-8H-indolo[3',2':4,5]pyrido[2,1-c] [1,4]benzodiazepine (13), demonstrated high affinity for the receptor, displacing both benzodiazepines (IC50 = 23 nM) and beta-carbolines (IC50 = 47 nM) from their binding sites. Of the compounds synthesized, 13 also most closely satisfied the structural requirements that generally ensure a high affinity of both beta-carbolines and benzodiazepines for the receptor (e.g., aromaticity of the beta-carboline, presence of a carbonyl at C-3 of the beta-carboline and of a pi 2-region on the benzodiazepine). The hybrids not fulfilling these requirements had no affinity for the receptor. In vivo pharmacological properties of 13 could not be demonstrated because of its metabolic instability and/or its poor transport into the brain. The results are discussed in terms of a possible overlapping of beta-carboline binding sites with those of benzodiazepines on the receptor.

Animals↗