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Journal of Food and Drug Analysis Jul 2018Pyrrolizidine alkaloids (PAs) are phytotoxins identified in over 6000 plant species worldwide. Approximately 600 toxic PAs and PA N-oxides have been identified in about... (Review)
Review
Pyrrolizidine alkaloids (PAs) are phytotoxins identified in over 6000 plant species worldwide. Approximately 600 toxic PAs and PA N-oxides have been identified in about 3% flowering plants. PAs can cause toxicities in different organs particularly in the liver. The metabolic activation of PAs is catalyzed by hepatic cytochrome P450 and generates reactive pyrrolic metabolites that bind to cellular proteins to form pyrrole-protein adducts leading to PA-induced hepatotoxicity. The mechanisms that pyrrole-protein adducts induce toxicities have not been fully characterized. Methods for qualitative and quantitative detection of pyrrole-protein adducts have been developed and applied for the clinical diagnosis of PA exposure and PA-induced liver injury. This mini-review addresses the mechanisms of PA-induced hepatotoxicity mediated by pyrrole-protein adducts, the analytical methods for the detection of pyrrole-protein adducts, and the development of pyrrole-protein adducts as the mechanism-based biomarker of PA exposure and PA-induced hepatotoxicity.
Topics: Animals; Biomarkers; Chemical and Drug Induced Liver Injury; Humans; Liver; Proteins; Pyrroles; Pyrrolizidine Alkaloids
PubMed: 29976414
DOI: 10.1016/j.jfda.2018.05.005 -
Digestive Diseases and Sciences Jul 2016
Topics: Humans; Proton Pump Inhibitors; Pyrroles; Sulfonamides
PubMed: 27074922
DOI: 10.1007/s10620-016-4164-8 -
Nanomedicine (London, England) Oct 2020This article is written to provide an up-to-date review of pyrrole-based biomedical materials. Porphyrins and other tetrapyrrolic molecules possess unique magnetic,... (Review)
Review
This article is written to provide an up-to-date review of pyrrole-based biomedical materials. Porphyrins and other tetrapyrrolic molecules possess unique magnetic, optical and other photophysical properties that make them useful for bioimaging and therapy. This review touches briefly on some of the synthetic strategies to obtain porphyrin- and tetrapyrrole-based nanoparticles, as well as the variety of applications in which crosslinked, self-assembled, porphyrin-coated and other nanoparticles are utilized. We explore examples of these nanoparticles' applications in photothermal therapy, drug delivery, photodynamic therapy, stimuli response, fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, computed tomography and positron emission tomography. We anticipate that this review will provide a comprehensive summary of pyrrole-derived nanoparticles and provide a guideline for their further development.
Topics: Nanoparticles; Optical Imaging; Photochemotherapy; Porphyrins; Pyrroles
PubMed: 32975469
DOI: 10.2217/nnm-2020-0125 -
Molecules (Basel, Switzerland) Aug 2022Bionanocomposites based on natural bioactive entities have gained importance due to their abundance; renewable and environmentally benign nature; and outstanding... (Review)
Review
Bionanocomposites based on natural bioactive entities have gained importance due to their abundance; renewable and environmentally benign nature; and outstanding properties with applied perspective. Additionally, their formulation with biological molecules with antimicrobial, antioxidant, and anticancer activities has been produced nowadays. The present review details the state of the art and the importance of this pyrrolic compound produced by microorganisms, with interest towards , including production strategies at a laboratory level and scale-up to bioreactors. Promising results of its biological activity have been reported to date, and the advances and applications in bionanocomposites are the most recent strategy to potentiate and to obtain new carriers for the transport and controlled release of prodigiosin. Prodigiosin, a bioactive secondary metabolite, produced by , is an effective proapoptotic agent against bacterial and fungal strains as well as cancer cell lines. Furthermore, this molecule presents antioxidant activity, which makes it ideal for treating wounds and promoting the general improvement of the immune system. Likewise, some of the characteristics of prodigiosin, such as hydrophobicity, limit its use for medical and biotechnological applications; however, this can be overcome by using it as a component of a bionanocomposite. This review focuses on the chemistry and the structure of the bionanocomposites currently developed using biorenewable resources. Moreover, the work illuminates recent developments in pyrrole-based bionanocomposites, with special insight to its application in the medical area.
Topics: Anti-Bacterial Agents; Bioreactors; Nanocomposites; Prodigiosin; Serratia marcescens
PubMed: 35956931
DOI: 10.3390/molecules27154982 -
Journal of the American Chemical Society Aug 2021Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores,...
Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles.
Topics: Azirines; Carbon; Density Functional Theory; Indoles; Molecular Structure; Pyrroles
PubMed: 34286965
DOI: 10.1021/jacs.1c06287 -
Cell Death & Disease Aug 2023Pancreatic cancer is a highly aggressive cancer, and is primarily treated with gemcitabine, with increasing resistance. SIRT6 as a member of sirtuin family plays...
Pancreatic cancer is a highly aggressive cancer, and is primarily treated with gemcitabine, with increasing resistance. SIRT6 as a member of sirtuin family plays important roles in lifespan and diverse diseases, such as cancer, diabetes, inflammation and neurodegenerative diseases. Considering the role of SIRT6 in the cytoprotective effect, it might be a potential anticancer drug target, and is associated with resistance to anticancer therapy. However, very few SIRT6 inhibitors have been reported. Here, we reported the discovery of a pyrrole-pyridinimidazole derivative, 8a, as a new non-competitive SIRT6 inhibitor, and studied its roles and mechanisms in the antitumor activity and sensitization of pancreatic cancer to gemcitabine. Firstly, we found a potent SIRT6 inhibitor compound 8a by virtual screening and identified by molecular and cellular SIRT6 activity assays. 8a could effectively inhibit SIRT6 deacetylation activity with IC values of 7.46 ± 0.79 μM in FLUOR DE LYS assay, and 8a significantly increased the acetylation levels of H3 in cells. Then, we found that 8a could inhibit the cell proliferation and induce cell apoptosis in pancreatic cancer cells. We further demonstrate that 8a sensitize pancreatic cancer cells to gemcitabine via reversing the activation of PI3K/AKT/mTOR and ERK signaling pathways induced by gemcitabine and blocking the DNA damage repair pathway. Moreover, combination of 8a and gemcitabine induces cooperative antitumor activity in pancreatic cancer xenograft model in vivo. Overall, we demonstrate that 8a, a novel SIRT6 inhibitor, could be a promising potential drug candidate for pancreatic cancer treatment.
Topics: Humans; Apoptosis; Cell Line, Tumor; Gemcitabine; Pancreatic Neoplasms; Phosphatidylinositol 3-Kinases; Pyrroles; Sirtuins; Xenograft Model Antitumor Assays
PubMed: 37542062
DOI: 10.1038/s41419-023-06018-1 -
The American Journal of Gastroenterology Aug 2023
Topics: Humans; Rifabutin; Cost-Benefit Analysis; Anti-Bacterial Agents; Pyrroles; Drug Therapy, Combination; Proton Pump Inhibitors; Helicobacter pylori
PubMed: 37094105
DOI: 10.14309/ajg.0000000000002248 -
Journal of Pharmacy & Pharmaceutical... 2022With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents... (Review)
Review
With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents need to be taken. Pyrrole moiety has been found in various active compounds with anti-inflammatory, antiseptic, antibacterial, lipid-lowering and anticancer properties. Recent advances in the exploration of highly active and selective cytotoxic structures containing pyrrole motifs have shown promising data for future investigations. Accordingly, this review presents an overview of recent developments in the pyrrole derivatives as anticancer agents, with a main focus towards the key moieties required for the anti-tumor activities. Pyrrole molecules comprising prominent targeting capacities against microtubule polymerization, tyrosine kinases, cytochrome p450 family 1, histone deacetylase and bcl-2 proteins were reported. In addition, several mechanisms of action, such as apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others were analyzed. Furthermore, in most of the discussed cases we provided synthesis schemes of the mentioned molecules. Overall, the utilization of pyrrole scaffold for the design and synthesis of novel anticancer drugs could be a promising approach for future investigations.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cytochrome P-450 Enzyme System; Genes, bcl-2; Histone Deacetylases; Humans; Microtubules; Protein-Tyrosine Kinases; Pyrroles; Structure-Activity Relationship
PubMed: 34995473
DOI: 10.18433/jpps32417 -
Chemistry (Weinheim An Der Bergstrasse,... Jan 2020Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin...
Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N-protected and protection-free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.
Topics: Catalysis; Imides; Indoles; Light; Pesticides; Pharmaceutical Preparations; Pyrroles
PubMed: 31596010
DOI: 10.1002/chem.201904168 -
Molecules (Basel, Switzerland) Sep 2022Benzimidazole is an important heterocyclic fragment, present in many biologically active compounds with a great variety of therapeutic purposes. Most of the... (Review)
Review
Benzimidazole is an important heterocyclic fragment, present in many biologically active compounds with a great variety of therapeutic purposes. Most of the benzimidazole activities are explained through the existence of 1,3-tautomeric equilibrium. As the binding affinity of each tautomer to a protein target depends on an established bioactive conformation, the effect of tautomers on the ligand protein binding mechanism is determinant. In this work, we searched and analyzed a series of reported C-NMR spectra of benzazoles and benzazolidine-2-thiones with the purpose of estimating their tautomeric equilibrium. Herein, several approaches to determine this problem are presented, which makes it a good initial introduction to the non-expert reader. This chemical shift difference and C4/C7 signals of benzimidazolidine-2-thione and 1-methyl-2-thiomethylbenzimidazole as references were used in this work to quantitatively calculate, in solution, the pyrrole-pyridine tautomeric ratio in equilibrium. The analysis will help researchers to correctly assign the chemical shifts of benzimidazoles and to calculate their intracyclic or exocyclic tautomeric ratio as well as mesomeric proportion in benzimidazoles.
Topics: Benzimidazoles; Ligands; Pyridines; Pyrroles; Thiones
PubMed: 36234805
DOI: 10.3390/molecules27196268