-
Marine Drugs Jul 2022Twelve new and four known alkaloids including five different structural scaffolds were isolated from the sponge collected in the South China Sea. Compound is the first...
Twelve new and four known alkaloids including five different structural scaffolds were isolated from the sponge collected in the South China Sea. Compound is the first identified precursor metabolite of the classic 5/7/5 tricyclic skeleton with unesterified guanidine and carboxyl groups, compounds - and - belong to the spongiacidin-type pyrrole imidazole alkaloids (PIAs). - and -configurations of the spongiacidin-type PIAs often appeared concomitantly and were distinguished by the chemical shift analysis of C NMR spectra. The structures of all twelve new compounds were determined by NMR, MS, and ECD analysis combined with single-crystal data of compounds , , and . In the aldose reductase (ALR2) inhibitory assay, six 5/7/5 tricyclic compounds (-, -) displayed significant activities. Compounds and , as the representative members of spongiacidin-PIAs, demonstrated their ALR2-targeted activities in SPR experiments with K values of 12.5 and 6.9 µM, respectively.
Topics: Alkaloids; Animals; Magnetic Resonance Spectroscopy; Molecular Structure; Porifera; Pyrroles
PubMed: 35877747
DOI: 10.3390/md20070454 -
Marine Drugs Dec 2018Two new sceptrin derivatives (,) and eight structurally-related known bromopyrrole-bearing alkaloids were isolated from the tropical sponge . By a combination of...
Two new sceptrin derivatives (,) and eight structurally-related known bromopyrrole-bearing alkaloids were isolated from the tropical sponge . By a combination of spectroscopic methods, the new compounds, designated dioxysceptrin () and ageleste C (), were determined to be structural analogs of each other that differ at the imidazole moiety. Dioxysceptrin was also found to exist as a mixture of α-amido epimers. The sceptrin alkaloids exhibited weak cytotoxicity against cancer cells. Compounds and also moderately exhibited anti-angiogenic and isocitrate lyase-inhibitory activities, respectively.
Topics: Agelas; Alkaloids; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Biological Products; Cell Line, Tumor; Drug Screening Assays, Antitumor; Enzyme Assays; Human Umbilical Vein Endothelial Cells; Humans; Isocitrate Lyase; Pyrroles; Stereoisomerism
PubMed: 30563015
DOI: 10.3390/md16120513 -
Molecules (Basel, Switzerland) Sep 2018The synthesis of four -functionalized bis[1]benzothieno[3,2-:2',3'-]pyrroles (BBTPs) is reported in order to provide a more detailed characterization of these fused-ring...
The synthesis of four -functionalized bis[1]benzothieno[3,2-:2',3'-]pyrroles (BBTPs) is reported in order to provide a more detailed characterization of these fused-ring units, as well as increase the scope of known BBTP units available for application to conjugated materials. The optical, electronic, and structural properties of the resulting BBTP units have been compared to the parent -alkyl- and -aryl-dithieno[3,2-:2',3'-]pyrroles (DTPs), as well as their corresponding 2,6-diphenyl derivatives, in order to fully quantify the relative electronic effects resulting from benzannulation of the parent DTP building block. Such comparative analysis reveals that benzannulation results in a red-shifted absorbance, but to a lesser extent than simple phenyl-capping of the DTP. More surprising is that benzannulation results in stabilization of the BBTP HOMO, compared to the destabilization normally observed with extending the conjugation length of the backbone.
Topics: Molecular Structure; Pyrroles; Thiophenes
PubMed: 30200588
DOI: 10.3390/molecules23092279 -
Molecules (Basel, Switzerland) Mar 2016In recent years, several synthetic strategies aiming at the peripheral functionalization of porphyrins were developed. Particularly interesting are those involving the... (Review)
Review
In recent years, several synthetic strategies aiming at the peripheral functionalization of porphyrins were developed. Particularly interesting are those involving the modification of β-pyrrolic positions leading to pyrrole-modified porphyrins containing four-, five-, six- or seven-membered heterocycles. Azeteoporphyrins, porpholactones and morpholinoporphyrins are representative examples of such porphyrinoids. These porphyrin derivatives have recently gained an increasing interest due to their potential application in PDT, as multimodal imaging contrast agents, NIR-absorbing dyes, optical sensors for oxygen, cyanide, hypochlorite and pH, and in catalysis.
Topics: Catalysis; Contrast Media; Humans; Molecular Structure; Multimodal Imaging; Porphyrins; Pyrroles
PubMed: 27005605
DOI: 10.3390/molecules21030320 -
Toxins Oct 2021Pyrrolizidine alkaloids (PAs) with 1,2-unsaturated necine base are hepatotoxic phytotoxins. Acute PA intoxication is initiated by the formation of adducts between...
Pyrrolizidine alkaloids (PAs) with 1,2-unsaturated necine base are hepatotoxic phytotoxins. Acute PA intoxication is initiated by the formation of adducts between PA-derived reactive pyrrolic metabolites with cellular proteins. The present study aimed to investigate the correlation between the formation of hepatic pyrrole-protein adducts and occurrence of PA-induced liver injury (PA-ILI), and to further explore the use of such adducts for rapidly screening the hepatotoxic potency of natural products which contain PAs. Aqueous extracts of (containing one PA: monocrotaline) and (containing two PAs: senecionine and seneciphylline) were orally administered to rats at different doses for 24 h to investigate PA-ILI. Serum alanine aminotransferase (ALT) activity, hepatic glutathione (GSH) level, and liver histological changes of the treated rats were evaluated to assess the severity of PA-ILI. The levels of pyrrole-protein adducts formed in the rats' livers were determined by a well-established spectrophotometric method. The biological and histological results showed a dose-dependent hepatotoxicity with significantly different toxic severity among groups of rats treated with herbal extracts containing different PAs. Both serum ALT activity and the amount of hepatic pyrrole-protein adducts increased in a dose-dependent manner. Moreover, the elevation of ALT activity correlated well with the formation of hepatic pyrrole-protein adducts, regardless of the structures of different PAs. The findings revealed that the formation of hepatic pyrrole-protein adducts-which directly correlated with the elevation of serum ALT activity-was a common insult leading to PA-ILI, suggesting a potential for using pyrrole-protein adducts to screen hepatotoxicity and rank PA-containing natural products, which generally contain multiple PAs with different structures.
Topics: Alanine Transaminase; Animals; Asteraceae; Chemical and Drug Induced Liver Injury; Crotalaria; Liver; Male; Plant Extracts; Proteins; Pyrroles; Pyrrolizidine Alkaloids; Rats, Sprague-Dawley; Rats
PubMed: 34679016
DOI: 10.3390/toxins13100723 -
Chemistry (Weinheim An Der Bergstrasse,... May 2020The degradation of chlorophyll, the omnipresent green pigment, has been investigated intensively over the last 30 years resulting in many elucidated tetrapyrrolic...
The degradation of chlorophyll, the omnipresent green pigment, has been investigated intensively over the last 30 years resulting in many elucidated tetrapyrrolic degradation products. With a comparison to the degradation of the structurally similar heme, we hereby propose a novel additional chlorophyll degradation mechanism to mono- and dipyrrolic products. This is the first proof of the occurrence of a family of mono- and dipyrrols in leaves that are previously only known as heme degradation products. This product family is also found in spit and feces of herbivores with specific metabolomic patterns reflecting the origin of the samples. Based on chromatographic and mass spectrometric evidence as well as on mechanistic considerations we also suggest several tentative new degradation products. One of them, dihydro BOX A, was fully confirmed as a novel natural product by synthesis and comparison of its spectroscopic data.
Topics: Chlorophyll; Herbivory; Plant Leaves; Plants; Pyrroles
PubMed: 31971638
DOI: 10.1002/chem.201905236 -
Toxins May 2022Pyrrolizidine alkaloids (PAs) have been found in over 6000 plants worldwide and represent the most common hepatotoxic phytotoxins. Catalyzed by hepatic cytochrome P450...
Pyrrolizidine alkaloids (PAs) have been found in over 6000 plants worldwide and represent the most common hepatotoxic phytotoxins. Catalyzed by hepatic cytochrome P450 enzymes, PAs are metabolized into reactive pyrrolic metabolites, which can alkylate cellular proteins and DNA to form pyrrole-protein adducts and pyrrole-DNA adducts, leading to cytotoxicity, genotoxicity, and tumorigenicity. To date, the correlation between these PA-derived pyrrole-protein and pyrrole-DNA adducts has not been well investigated. Retrorsine is a representative hepatotoxic and carcinogenic PA. In the present study, the correlations among the PA-derived liver DNA adducts, liver protein adducts, and serum protein adducts in retrorsine-treated mice under different dosage regimens were studied. The results showed positive correlations among these adducts, in which serum pyrrole-protein adducts were more accessible and present in higher abundance, and thus could be used as a suitable surrogate biomarker for pyrrole-DNA adducts to indicate the genetic or carcinogenic risk posed by retrorsine.
Topics: Animals; Carcinogens; DNA; DNA Adducts; Liver; Male; Mice; Mice, Inbred ICR; Proteins; Pyrroles; Pyrrolizidine Alkaloids
PubMed: 35737038
DOI: 10.3390/toxins14060377 -
Angewandte Chemie (International Ed. in... Apr 2016Axinellamines A and B are broad-spectrum antibacterial pyrrole-imidazole alkaloids that have a complex polycyclic skeleton. A new asymmetric synthesis of these marine...
Axinellamines A and B are broad-spectrum antibacterial pyrrole-imidazole alkaloids that have a complex polycyclic skeleton. A new asymmetric synthesis of these marine sponge metabolites is described herein, featuring an oxidative rearrangement and an anchimeric chlorination reaction.
Topics: Imidazoles; Isomerism; Pyrroles
PubMed: 27037993
DOI: 10.1002/anie.201600007 -
Molecular & Cellular Proteomics : MCP Oct 20174-Oxo-2-nonenal (ONE) derived from lipid peroxidation modifies nucleophiles and transduces redox signaling by its reactions with proteins. However, the molecular...
4-Oxo-2-nonenal (ONE) derived from lipid peroxidation modifies nucleophiles and transduces redox signaling by its reactions with proteins. However, the molecular interactions between ONE and complex proteomes and their dynamics remain largely unknown. Here we describe a quantitative chemoproteomic analysis of protein adduction by ONE in cells, in which the cellular target profile of ONE is mimicked by its alkynyl surrogate. The analyses reveal four types of ONE-derived modifications in cells, including ketoamide and Schiff-base adducts to lysine, Michael adducts to cysteine, and a novel pyrrole adduct to cysteine. ONE-derived adducts co-localize and exhibit crosstalk with many histone marks and redox sensitive sites. All four types of modifications derived from ONE can be reversed site-specifically in cells. Taken together, our study provides much-needed mechanistic insights into the cellular signaling and potential toxicities associated with this important lipid derived electrophile.
Topics: Aldehydes; Amides; Cell Line; Cysteine; Histone Code; Humans; Lipid Peroxidation; Lysine; Oxidation-Reduction; Proteome; Proteomics; Pyrroles; Schiff Bases
PubMed: 28814509
DOI: 10.1074/mcp.RA117.000116 -
Zeitschrift Fur Naturforschung. C,... 2007The pyrrole derivatives la, b and 2a, b were used as precursors for the preparation of N-substituted pyrrole derivatives 3a, b-9a, b and pyrrolo[2,3-d]pyrimidines 13-16....
The pyrrole derivatives la, b and 2a, b were used as precursors for the preparation of N-substituted pyrrole derivatives 3a, b-9a, b and pyrrolo[2,3-d]pyrimidines 13-16. Also, all the newly prepared products were tested for anti-inflammatory activity as analogues to fenamates, and some of them revealed moderate anti-inflammatory activity compared to the standard drug indomethacin.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Models, Molecular; Molecular Structure; Pyrimidines; Pyrroles; Rats
PubMed: 17425101
DOI: 10.1515/znc-2007-1-205