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Zeitschrift Fur Naturforschung. C,... Apr 2018Fifteen pyrrole alkaloids were isolated from the Red Sea marine sponge Stylissa carteri and investigated for their biological activities. Four of them were dibrominated...
Fifteen pyrrole alkaloids were isolated from the Red Sea marine sponge Stylissa carteri and investigated for their biological activities. Four of them were dibrominated [(+) dibromophakelline, Z-3-bromohymenialdisine, (±) ageliferin and 3,4-dibromo-1H-pyrrole-2-carbamide], nine compounds were monobrominated [(-) clathramide C, agelongine, (+) manzacidin A, (-) 3-bromomanzacidin D, Z-spongiacidin D, Z-hymenialdisine, 2-debromostevensine, 2-bromoaldisine and 4-bromo-1H-pyrrole-2-carbamide)] and finally, two compounds were non-brominated derivatives viz., E-debromohymenialdisine and aldisine. The structure elucidations of isolated compounds were based on 1D & 2D NMR spectroscopic and MS studies, as well as by comparison with literature. In-vitro, Z-spongiacidin D exhibited a moderate activity on (ARK5, CDK2-CycA, CDK4/CycD1, VEGF-R2, SAK and PDGFR-beta) protein kinases. Moreover, Z-3-bromohymenialdisine showed nearly similar pattern. Furthermore, Z-hymenialdisine displayed a moderate effect on (ARK5 & VEGF-R2) and (-) clathramide C showed a moderate activity on AURORA-A protein kinases. While, agelongine, (+) manzacidin A, E-debromohymenialdisine and 3,4-dibromo-1H-pyrrole-2-carbamide demonstrated only marginal inhibitory activities. The cytotoxicity study was evaluated in two different cell lines. The most effective secondary metabolites were (+) dibromophakelline and Z-3-bromohymenialdisine on L5178Y. Finally, Z-hymenialdisine, Z-3-bromohymenialdisine and (±) ageliferin exhibited the highest cytotoxic activity on HCT116. No report about inhibition of AURORA-A and B by hymenialdisine/hymenialdisine analogs existed and no reported toxicity of ageliferin existed in literature.
Topics: Alkaloids; Animals; Cell Line; Cell Survival; Drug Screening Assays, Antitumor; HCT116 Cells; Humans; Indian Ocean; Molecular Structure; Porifera; Pyrroles
PubMed: 29353267
DOI: 10.1515/znc-2017-0161 -
ACS Chemical Neuroscience Apr 2021Serotonin type 6 receptor (5-HTR) has gained particular interest as a promising target for treating cognitive deficits, given the positive effects of its antagonists in...
Serotonin type 6 receptor (5-HTR) has gained particular interest as a promising target for treating cognitive deficits, given the positive effects of its antagonists in a wide range of memory impairment paradigms. Herein, we report on degradation of the 1-pyrrolo[3,2-]quinoline scaffold to provide the 2-phenyl-1-pyrrole-3-carboxamide, which is devoid of canonical indole-like skeleton and retains recognition of 5-HTR. This modification has changed the compound's activity at 5-HTR-operated signaling pathways from neutral antagonism to inverse agonism. The study identified compound that behaves as an inverse agonist of the 5-HTR at the Gs and Cdk5 signaling pathways. Compound showed high selectivity and metabolic stability and was brain penetrant. Finally, reversed scopolamine-induced memory decline in the novel object recognition test and exhibited procognitive properties in the attentional set-shifting task in rats. In light of these findings, might be considered for further evaluation as a new cognition-enhancing agent, while 2-phenyl-1-pyrrole-3-carboxamide might be used as a template for designing 5-HTR inverse agonists.
Topics: Animals; Cognition; Pyrroles; Rats; Receptors, Serotonin; Structure-Activity Relationship
PubMed: 33705101
DOI: 10.1021/acschemneuro.1c00061 -
ChemMedChem Jan 2022Taspase1 is a unique protease not only pivotal for embryonic development but also implicated in leukemia as well as solid tumors. As such, it is a promising target in...
Taspase1 is a unique protease not only pivotal for embryonic development but also implicated in leukemia as well as solid tumors. As such, it is a promising target in cancer therapy, although only a limited number of Taspase1 inhibitors lacking general applicability are currently available. Here we present a bivalent guanidiniocarbonyl-pyrrole (GCP)-containing supramolecular ligand that is capable of disrupting the essential interaction between Taspase1 and its cognate import receptor Importin α in a concentration-dependent manner in vitro with an IC of 35 μM. Here, size of the bivalent vs the monovalent construct as well as its derivation with an aromatic cbz-group arose as critical determinants for efficient interference of 2GC. This was also evident when we investigated the effects in different tumor cell lines, resulting in comparable EC values (∼40-70 μM). Of note, in higher concentrations, 2GC also interfered with Taspase1's proteolytic activity. We thus believe to set the stage for a novel class of Taspase1 inhibitors targeting a pivotal protein-protein interaction prerequisite for its cancer-associated proteolytic function.
Topics: Dose-Response Relationship, Drug; Endopeptidases; Guanidine; Humans; Ligands; Molecular Structure; Protease Inhibitors; Pyrroles; Structure-Activity Relationship; alpha Karyopherins
PubMed: 34623765
DOI: 10.1002/cmdc.202100640 -
Molecules (Basel, Switzerland) Jan 2021Nitro-substituted π-electronic molecules are fascinating because of their unique electronic and optical properties and the ease of their transformation into various...
Nitro-substituted π-electronic molecules are fascinating because of their unique electronic and optical properties and the ease of their transformation into various functional derivatives. Herein, nitro-introduced dipyrrolyldiketone BF complexes as anion-responsive π-electronic molecules were synthesized, and their electronic properties and anion-binding abilities were investigated by spectroscopic analyses and theoretical studies. The obtained nitro-substituted derivatives showed solvent-dependent UV/vis spectral changes and high anion-binding affinities due to the easily pyrrole-inverted conformations and polarized pyrrole NH sites upon the introduction of electron-withdrawing moieties.
Topics: Anions; Electronics; Electrons; Ketones; Nitro Compounds; Pyrroles; Spectrophotometry, Ultraviolet
PubMed: 33498695
DOI: 10.3390/molecules26030595 -
The American Journal of Gastroenterology Nov 2022
Topics: Humans; Pyrroles; Sulfonamides; Hydrogen-Ion Concentration; Proton Pump Inhibitors
PubMed: 35849632
DOI: 10.14309/ajg.0000000000001905 -
American Family Physician Sep 2021
Meta-Analysis
Topics: Helicobacter Infections; Helicobacter pylori; Humans; Network Meta-Analysis; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome
PubMed: 34523899
DOI: No ID Found -
Biosensors May 2022We synthesized core-shell-shaped nanocomposites composed of a single-walled carbon nanotube (SWCNT) and heptadecafluorooctanesulfonic acid-doped polypyrrole...
We synthesized core-shell-shaped nanocomposites composed of a single-walled carbon nanotube (SWCNT) and heptadecafluorooctanesulfonic acid-doped polypyrrole (C8F-doped-PPy)/phenyllatic acid (PLA), i.e., C8F-doped-PPy/PLA@SWCNT, for detecting acetone gas with high sensitivity and humidity stability. The obtained nanocomposites have the structural features of a sensing material as a C8F-doped-PPy layer surrounding a single-stranded SWCNT, and a PLA layer on the outer surface of the PPy as a specific sensing layer for acetone. PLA was chemically combined with the positively charged PPy backbone and provided the ability to reliably detect acetone gas at concentrations as low as 50 ppb even at 25 °C, which is required for medical diagnoses via human breath analysis. When C8F was contained in the pyrrole monomer in a ratio of 0.1 mol, it was able to stably detect an effective signal in a relative humidity (RH) of 0-80% range.
Topics: Acetone; Humans; Humidity; Lactates; Nanocomposites; Polyesters; Polymers; Pyrroles
PubMed: 35624655
DOI: 10.3390/bios12050354 -
Angewandte Chemie (International Ed. in... Sep 2022indolizidine alkaloids of unusual biosynthetic origin have recently been characterized from several species of fungi within the Pleosporaceae family. Possessing distinct...
indolizidine alkaloids of unusual biosynthetic origin have recently been characterized from several species of fungi within the Pleosporaceae family. Possessing distinct polycyclic architectures with two embedded electron-rich pyrroles as well as reported antibacterial activity against gram positive and negative pathogens, these natural products represent attractive targets for total synthesis. Herein we survey the differential functionalization of a chemically sensitive bispyrrole framework resulting in the preparation of multiple bipolamine alkaloids, work which sheds light on their innate chemical reactivity and potential biosynthetic relationships.
Topics: Alkaloids; Ascomycota; Biological Products; Bipolaris; Pyrroles
PubMed: 35866193
DOI: 10.1002/anie.202209457 -
Molecules (Basel, Switzerland) Mar 2021An efficient method for the synthesis of pharmaceutically prospective pyrrole-aminopyrimidine ensembles (in up to 91% yield) by the cyclocondensation of easily available...
An efficient method for the synthesis of pharmaceutically prospective pyrrole-aminopyrimidine ensembles (in up to 91% yield) by the cyclocondensation of easily available acylethynylpyrroles with guanidine nitrate has been developed. The reaction proceeds under heating (110-115 °C, 4 h) in the KOH/DMSO system. In the case of 2-benzoylethynylpyrrole, the unexpected addition of the formed pyrrole-aminopyrimidine as N- (NH moiety of the pyrrole ring) and C- (CH of aminopyrimidine) nucleophiles to the triple bond is observed.
Topics: Cycloaddition Reaction; Dimethyl Sulfoxide; Guanidines; Hot Temperature; Hydroxides; Potassium Compounds; Pyrimidines; Pyrroles
PubMed: 33803018
DOI: 10.3390/molecules26061692 -
Marine Drugs Nov 2009In his most celebrated tale "The Picture of Dorian Gray", Oscar Wilde stated that "those who go beneath the surface do so at their peril". This sentence could be a... (Review)
Review
In his most celebrated tale "The Picture of Dorian Gray", Oscar Wilde stated that "those who go beneath the surface do so at their peril". This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity--from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products.
Topics: Alkaloids; Animals; Imidazoles; Marine Biology; Porifera; Pyrroles
PubMed: 20098608
DOI: 10.3390/md7040705