Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PYRROLES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1992

Subacute toxicity of a halogenated pyrrole hydroxymethylglutaryl-coenzyme A reductase inhibitor in Wistar rats.

Wistar rats received an hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, a halogenated pyrrole designated PD 123244-15, orally by gavage for 14 days at 10, 50, 150, 300, and 600 mg/kg. Doses of 150-600 mg/kg caused death and marked systemic toxicity involving stomach, esophagus, liver, gonads, lymphoid tissues, and skeletal muscle. Histopathologic findings included hyperkeratosis in esophagus and forestomach, increased hepatic mitotic activity, ovarian follicular necrosis, testicular atrophy and arrested spermatogenesis, and skeletal muscle necrosis and regeneration. Elevated serum aspartate aminotransferase correlated with muscle necrosis and hepatocellular damage. Marked systemic effects associated with high plasma concentrations were consistent with toxicity defined for other HMG-CoA reductase inhibitors, with the exception of pathologic alterations in the esophagus and ovaries. Direct mucosal irritation may have contributed to forestomach and esophageal lesions induced by this halogenated pyrrole.

Animals↗
PubMed1996

Pyrrole detection and the pathologic progression of Cynoglossum officinale (houndstongue) poisoning in horses.

Houndstongue (Cynoglossum officinale), a noxious weed that contains pyrrolizidine alkaloids (PAs), infests pastures and fields in the western United States and Europe. The purpose of this study was to develop techniques to better diagnose PA poisoning and describe the progression of gross and microscopic lesions caused by houndstongue intoxication. Six horses were gavaged daily with a suspension of houndstongue containing 5 or 15 mg/kg total PA for 14 days. Two horses were treated similarly with ground alfalfa as controls. Liver biopsy samples and serum biochemical and hematologic values were evaluated biweekly. Within 7 days after dosing, horses treated with 15 mg/kg PA developed severe liver disease characterized by altered bile acid metabolism, elevated serum enzymes, and extensive hepatocellular necrosis with minimal periportal fibrosis and biliary hyperplasia. The condition of these animals continued to deteriorate, and they were euthanized. For several weeks after dosing, horses treated with 5 mg/kg PA were depressed, had transient elevations of serum enzymes and bile acids, and developed minimal periportal hepatocellular necrosis with fibrosis. The biochemical changes resolved by 6-8 weeks; however, the histologic disease persisted with extensive megalocytosis by week 14. Throughout the study, the rate of hepatocellular proliferation remained constant. Biliary cells had an increase in mitotic rate that correlated with the histologic changes. Hepatic tissue-bound pyrroles (PA metabolites) were identified in necropsy samples of treated animals using gas chromatography/mass spectrometry and photometrically with Ehrlich's reagent. These findings suggest that pyrrole extraction and identification are useful in documenting PA exposure and that houndstongue is extremely toxic to horses.

Alkaloids↗
PubMed1989

Synthesis, structure and cytostatic activity of a series of N-substituted 3,4-diphenyl-1H-pyrrole-2,5-diones.

A series of N-substituted 3,4-diphenyl-1H-pyrrole-2,5-diones (diphenylmaleimides) (IV) were synthesized and tested for cytostatic activity. Compounds IVa--k were prepared from diphenylmaleic anhydride or its dinitro derivative (V or VI) and the corresponding amine. Compounds IVl--n were obtained by reaction of 3-(p-nitrophenyl)-4-phenyl-1H-pyrrole-2,5-dione potassium salt with the appropriate chloroalkylamine. Hydrogenation of IVl,n gave the the corresponding cis-3-(p-aminophenyl)-4-phenylsuccinimides (VIIIa,b). The structure-cytostatic activity relationship of these compounds is discussed.

Antineoplastic Agents↗
PubMed2005

Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes.

During the development of new nonsteroidal anti-inflammatory agents, it was discovered that 1-aminoalkyl-3-aroylindoles have affinity for the cannabinoid brain (CB(1)) receptor. This has led to the development of over 100 cannabimimetic aminoalkylindoles, and the development of SAR for these compounds. Later work demonstrated that the aminoalkyl moiety was not necessary, and could be replaced by a four- to six-membered alkyl chain without loss of affinity. Investigation of these indoles led to the discovery of a CB(2) selective ligand, 3-(1-naphthoyl)-N-propylindole. Subsequent work has provided several additional CB(2) selective indoles. On the basis of a proposed pharmacophore for the cannabimimetic indoles, a series of pyrroles and indenes were developed, some of which are potent cannabinoids. SAR for several series of pyrroles have been developed. Two groups have described cannabimimetic indenes, which have been employed as rigid models for the receptor interactions of cannabimimetic indoles with the CB(1) receptor. There is some evidence that the indoles bind to a somewhat different site on the receptor than traditional cannabinoids, and interact with the receptor primarily by aromatic stacking.

Animals↗
PubMed2005

Modelling of aldose reductase inhibitory activity of pyrrol-1-yl-acetic acid derivatives by means of multivariate statistics.

The inhibition of the aldose reductase enzyme (AR) is considered to be a promising approach to control chronic diabetes complications as well as a number of other pathological conditions. Thus considerable efforts are devoted to the development of aldose reductase inhibitors (ARIs) as possible pharmacotherapeutic agents. The establishment of adequate QSAR models would serve to this purpose. In the present study multivariate statistics was applied in order to analyse the AR inhibitory activity data of twenty three pyrrol-1-yl-acetic acid derivatives on the basis of essential molecular descriptors. The compounds contain one or two carbonyl keto groups, which serve as a bridge to link the pyrrole moiety to aromatic nuclei with or without further substitution. An adequate one component model with satisfactory statistics was obtained and validated for its robustness and predictive ability. The influence of the different descriptors in ARI activity is discussed. The derived model was further used to predict the activity of four independent compounds and the contribution of their specific structural characteristics in ARI activity was evaluated.

Acetic Acid↗
PubMed1987

Metabolic oxidation of the pyrrole ring: structure and origin of some urinary metabolites of the anti-hypertensive pyrrolylpyridazinamine, mopidralazine. III: Studies with the 13C-labelled drug.

The metabolism of the anti-hypertensive drug, mopidralazine, N-(2',5'-dimethyl-1H-pyrrol-1-yl)-6-(4"-morpholinyl)-3-pyridazinamine, was reinvestigated in rats using the [2'(5')-13CH3]-labelled drug to determine the significance of the pharmacologically active intermediate 3-hydrazino-6-(4-morpholinyl)pyridazine. The previously proposed mesonic structure of the major metabolite I, i.e., 5'-hydroxy-3',6'-dimethyl-1'-[6-(4"-morpholinyl)-3-pyridazinyl]pyrida zinium hydroxide inner salt, was confirmed by chemical synthesis, X-ray diffraction analysis and 1H n.m.r. of the [3',6'-13CH3]-labelled metabolite I. Metabolite II, 3-methyl-6-(4-morpholinyl)-triazolo [4,3-6 b]pyridazine and metabolite VII, 3-methyl-7-(4-morpholinyl)-3H-pyridazino[1,6-c]pyridazine, were shown to retain the 13CH3 labelling of mopidralazine, whereas metabolite X, 3-acetyl-hydrazino-6-(4-morpholinyl)-pyridazine, loses the labelling, indicating that their formation involves two different pathways. It is hypothesized that the oxidation of the pyrrole leads to ring opening followed by a chemical rearrangement giving rise directly to metabolites II and VII or, with the intermediacy of the pharmacologically active 3-hydrazino-6-(4-morpholinyl) derivative and an enzymic acetylation or conjugation with pyruvic acid, to metabolites X, II and VII.

Animals↗
PubMed1992

Microsomal formation of a pyrrolic alcohol glutathione conjugate of the pyrrolizidine alkaloid senecionine.

1. Pyrrolizidine alkaloids (PAs) are metabolized primarily to putative dehydroalkaloid (PA pyrrole) metabolites and to PA N-oxide by rat liver microsomal monooxygenases. 2. The dehydroalkaloids are highly reactive and either bind covalentely to tissue nucleophiles or are hydrolysed to the more stable pyrrole, (R,S)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), and the corresponding necic acid. 3. Addition of glutathione (GSH 1 mM) to incubation mixtures containing rat liver microsomes and the PA senecionine (SN), resulted in the formation of a conjugate of DHP with GSH. 5. The mass spectrum of this DHP-GSH conjugate was identical to that of the chemically-synthesized dehydroretronecine (the R enantiomer of the racemic DHP) and GSH. 6. Only negligible amounts of DHP-GSH conjugate were formed when DHP itself was incubated with GSH at physiological pH. 7. These findings provide strong evidence for the microsomal conversion of SN to a highly reactive metabolite, presumably dehydrosenecionine, which then reacts with GSH to form the DHP-GSH conjugate. 8. It is likely that a similar mechanism is responsible in vivo for the formation of GSH conjugates of DHP from SN and other PAs.

Alcohols↗
PubMed1999

The cytotoxicity and mode of action of 2,3,4-trisubstituted pyrroles and related derivatives in human Tmolt4 leukemia cells.

4-Carbethoxy-1-methyl-2-phenacyl-3-phenylpyrrole (9), 4-carbethoxy-2-(4-methoxybenzoyl)-3-(4-methoxyphenyl)pyrrole (10) and 2-(4-methoxybenzoyl)-3,4-bis-(4-methoxyphenyl)pyrrole (11) proved to be potent cytotoxic agents against the growth of murine and human leukemias and lymphomas. Selective toxicity was demonstrated against the growth of solid tumors, e.g., human adenocarcinoma of the colon SW480 and ileum HCT-8, glioma U-87-MG, and rat UMR-106 osteosarcoma. A mode of action study in Tmolt4 leukemia cells demonstrated that the agents inhibited de novo purine synthesis at the regulatory sites PRPP-amido transferase, IMP dehydrogenase as well as dihydrofolate reductase resulting in significant inhibition of DNA synthesis in 60 min. Other biochemical sites which were affected significantly were thymidylate synthetase, DNA polymerase alpha, RNA polymerases, nucleoside kinase and ribonucleoside reductase.

Animals↗
PubMed2000

Macrophage receptors responsible for distinct recognition of low density lipoprotein containing pyrrole or pyridinium adducts: models of oxidized low density lipoprotein.

Oxidation of low density lipoproteins (LDL) induced by incubation with Cu(2+) ions results in the formation of a heterogeneous group of aldehydic adducts on lysyl residues (Lys) of apolipoprotein B (apoB) that are thought to be responsible for the uptake of oxidized LDL (oxLDL) by macrophages. To define the structural and chemical criteria governing such cell recognition, we induced two modifications of lysines in LDL that mimic prototypic adducts present in oxLDL; namely, epsilon-amino charge-neutralizing pyrrolation by treatment with 2,5-hexanedione (hdLDL), and epsilon-amino charge-retaining pyridinium formation via treatment with 2,4,6-trimethylpyrylium (tmpLDL). Both modifications led to recognition by receptors on mouse peritoneal macrophages (MPM). To assess whether the murine scavenger receptor class A-I (mSR-A) was responsible for recognition of hdLDL or tmpLDL in MPM, we measured binding at 4 degrees C and degradation at 37 degrees C of these modified forms of (125)I-labeled LDL by mSR-A-transfected CHO cells. Although uptake and degradation of hdLDL by mSR-A-transfected CHO cells was quantitatively similar to that of the positive control, acLDL, tmpLDL was not recognized by these cells. However, both tmpLDL and hdLDL were recognized by 293 cells that had been transfected with CD36. In the human monocytic cell line THP-1 that had been activated with PMA, uptake of tmpLDL was significantly inhibited by blocking monoclonal antibodies to CD36, further suggesting recognition of tmpLDL by this receptor. Macrophage uptake and degradation of LDL oxidized by brief exposure to Cu(2+) was inhibited more effectively by excess tmpLDL and hdLDL than was more extensively oxidized LDL, consistent with the recognition of the former by CD36 and the latter primarily by SR-A.Collectively, these studies suggest that formation of specific pyrrole adducts on LDL leads to recognition by both the mSR-A and mouse homolog of CD36 expressed on MPM, while formation of specific pyridinium adducts on LDL leads to recognition by the mouse homolog of CD 36 but not by mSR-A. As such, these two modifications of LDL may represent useful models for dissecting the relative contributions of specific modifications on LDL produced during oxidation, to the cellular uptake of this heterogeneous ligand.

Animals↗
PubMedDate not supplied

Synthesis of new pyrroles and their biological activities.

Coumarino acid hydrazides and acid hydrazide of 2-oxy 3, 5, 6-trichloropyridine were prepared in two steps. These acid hydrazides on condensation with Acetonyl acetone i.e. 2,5-hexanedione yields new pyrroles. These pyrroles showed good to moderate antimicrobial activities against Alternaria brassicicola, Aspergillus niger, E. coli and Lactobacillus.

Anti-Infective Agents↗
PubMed2003

Pentapyrrolic calix[4]pyrrole.

A new calix[4]pyrrole has been synthesised that contains a 3,4,5-trisbromopyrrole appended to a meso-position which shows enhanced anion affinity as compared to the parent meso-octamethylcalix[4]pyrrole macrocycle.

Calixarenes↗
PubMed2004

A novel antifungal pyrrole derivative from Datura metel leaves.

Phytochemical investigation of the leaves of Datura metel Linn. led to the isolation of a new pyrrole derivative 1 which was characterised as 2beta-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1'-methylethyl pentanoate on the basis of spectral data analyses and chemical reactions. Compound 1 was endowed with antifungal activity and its MIC was found to be 87.5 microg/ml. Two proteins having molecular weights of 42 and 58 kD of Aspergillus fumigatus are potential targets for compound 1.

Antifungal Agents↗
PubMed1991

Tricyclic heteroaromatic systems. Synthesis of 1,3 and 1,2 disubstituted [1]benzopyrano[4,3-b]pyrrol-4-ones and structure-activity relationships as benzodiazepine receptor ligands.

The synthesis of some 1,3- and 1,2- disubstituted [1]benzopyrano-pyrrol-4-ones is reported as well as their benzodiazepine receptor affinity, as measured by the ability to displace [3H]flunitrazepam from its specific central binding. The structure-activity relationships on the whole series of disubstituted [1]benzopyrano-pyrrol-4-ones show the importance of the presence of the 1-aryl substituent and the size limitation of the 3-substituent. The size of the latter seems also to be important for the "in vitro" efficacy.

Animals↗
PubMed1986

[Non-steroidal anti-inflammatory agents. IV. Synthesis and pharmacologic activity of aroylthiopheneacetic acids with a pyrrole group].

The synthesis of new antiinflammatory aroylthiopheneacetic acids bearing a pyrrole moiety is described. These compounds can be regarded as analogues of thiaprofen and related isosteres. The antiinflammatory activity of the new pyrryl derivatives has been evaluated in comparison with indomethacin, tolmetin and the unknown 5-(2-chlorobenzoyl)thiophene-2-acetic acid. Among tested derivatives the compounds containing the pyrrole ring were devoid of analgesic-antiinflammatory activities.

Animals↗
PubMed1994

Structure-activity relationship of a series of nitrogen mustard- and pyrrole-containing minor groove-binding agents related to distamycin.

Two series of tethered nitrogen mustards based on the minor groove-binding and A/T sequence-specific natural product distamycin have been synthesized and evaluated. The conjugates, which have a modified dimethylamino C-terminus, are comprised of one, two or three pyrrole carboxamide units linked to either benzoic acid mustard (BAM) or chlorambucil (CHL). The DNA binding properties, in vitro cytotoxicities and DNA cross-linking abilities were determined for each of the conjugates. The conjugates were found to bind preferentially to poly(dA.dT) compared to poly(dG.dC) DNA by ethidium displacement and circular dichroism. The di- and tripyrrole conjugates had higher binding affinities than the monopyrrole conjugates. All the conjugates were more cytotoxic than the nitrogen mustards themselves. Cytotoxicity increased with the increase from one to three pyrrole units and the CHL conjugates were more cytotoxic than the corresponding BAM analogues. The CHL conjugates were able to cross-link plasmid DNA at a 10-fold lower dose than CHL itself. The BAM conjugates showed < 10% cross-linking at doses which gave 100% cross-linking with the CHL conjugates. In cells, the CHL conjugates showed significant cross-linking at the IC50 values, while the BAM conjugates showed no evidence of cross-link formation even at 10 times the IC50 value. These results are discussed in reference to a series of previously reported GC-recognizing imidazole analogues possessing the same nitrogen mustard groups.

Alkylating Agents↗
PubMed2004

Reactions of substituted (1,3-butadiene-1,4-diyl)magnesium, 1,4-bis(bromomagnesio)butadienes and 1,4-dilithiobutadienes with ketones, aldehydes and PhNO to yield cyclopentadiene derivatives and N-Ph pyrroles by cyclodialkenylation.

1,4-Dilithiobutadiene derivatives 1, 1,4-bis(bromomagnesio)butadiene derivatives 2 and metallacyclic (1,3-butadiene-1,4-diyl)magnesium reagents 3 were prepared and their reactions with ketones, aldehydes, and PhNO were investigated. Multiply substituted cyclopentadienes and N-Ph pyrroles were formed by unprecedented reaction conditions. The carbonyl group of aldehydes and ketones was deoxygenated during the reaction and behaved formally as a one-carbon unit; the N==O moiety of PhNO was cleaved to afford N-Ph pyrrole derivatives. Furthermore, different reactivities among these three types of reagents 1, 2 and 3 were revealed. The 1,4-dilithium reagents 1 readily reacted with both aldehydes and ketones; the 1,4-dimagnesium reagents 2 reacted with aldehydes, but not ketones; the metallacyclopentadiene reagents of magnesium 3 showed higher reactivity and did react with ketones.

Journal Article↗
PubMed2004

Crown-tetrathiafulvalenes attached to a pyrrole or an EDOT unit: synthesis, electropolymerization and recognition properties.

A crown-tetrathiafulvalene electroactive receptor has been covalently linked to electropolymerizable pyrrole or 3,4-ethylenedioxythiophene monomers. The synthetic route to the monofonctionalized tetrathiafulvalene (TTF) ligand has been optimized. Two derivatives of pyrrole (N- and 3-substituted) were synthesized. The various substituted monomers have been electropolymerized to produce polypyrrole (PP) and poly(ethylenedioxothiophene) (PEDOT) films bearing the electroactive TTF moiety. The electroactivity of the polymer films is efficiently controlled by the well-defined two-step redox behavior of the TTF unit. In the case of PEDOT, an alternative post-polymerization derivatization strategy has been used, involving the grafting of the crown-TTF ligand on the previously grown PEDOT backbone. Though chemical derivatization is realized under heterogeneous conditions, in the bulk of the film, this strategy proved to be particularly efficient. These electrodes constitute the first examples of conducting polymer-based modified electrodes incorporating a TTF electrochemical probe, able to interact with a guest ion, such as Ba2+. The cation recognition properties of these various electrodes have been analyzed by cyclic voltammetry and their electroactivity in water as well as their regeneration capability have been investigated.

Journal Article↗