LC–MS/MS reveals the formation of iminium and quinone methide reactive intermediates in entrectinib metabolism: In vivo and in vitro metabolic investigation

2018 ◽  
Vol 160 ◽  
pp. 19-30 ◽  
Author(s):  
Mohamed W. Attwa ◽  
Adnan A. Kadi ◽  
Haitham Alrabiah ◽  
Hany W. Darwish
Keyword(s):  
Reactive Intermediates ◽  
Quinone Methide ◽  
Metabolic Investigation

Studies on the dehydrogenative polymerization of monolignol β-glycosides. Part 6: Monitoring of horseradish peroxidase-catalyzed polymerization of monolignol glycosides by GPC-PDA

Holzforschung ◽  
2010 ◽  
Vol 64 (2) ◽  
Author(s):  
Yuki Tobimatsu ◽  
Toshiyuki Takano ◽  
Hiroshi Kamitakahara ◽  
Fumiaki Nakatsubo
Keyword(s):  
Horseradish Peroxidase ◽  
Reaction System ◽  
Water Soluble ◽  
Quinone Methide ◽  
Efficient Production ◽  
Hydroxyl Groups ◽  
Photodiode Array Detection ◽  
Dehydrogenative Polymerization

Abstract Horseradish peroxidase (HRP)-catalyzed dehydrogenative polymerization of guaiacyl (G) and syringyl (S)-type monolignol γ-O-glucosides, isoconiferin (iso-G) and isosyringin (iso-S), which contain a hydrophilic glucosyl unit on γ-position of coniferyl alcohol and sinapyl alcohol, respectively, was monitored by gel permeation chromatography coupled with photodiode array detection (GPC-PDA). Contrary to the conventional dehydrogenative polymerization of monolignols, the polymerization of the glycosides produces water-soluble synthetic lignins (DHPs) in a homogeneous aqueous phase. Taking advantage of this unique reaction system, the method was developed to follow the changes of molecular weights in the course of DHP formations. Moreover, PDA detection permits determination of oligomeric S-type quinone methide intermediates (QMs) formed as stable transient compounds during polymerization of iso-S. A detailed comparison of the polymerization profiles revealed entirely different behaviors of G- and S-type monomers. The data strongly support the view that the low reactivity of oligomeric S-type QMs impedes the formation of DHPs from S-type monomers. In copolymerization of G- and S-type monomers, it is conceivable that G-type phenolic hydroxyl groups serve as good nucleophilic reactants to scavenge S-type QMs resulting in efficient production of DHPs. As a consequence, the present approach can be a powerful tool to study the in vitro dehydrogenative polymerization providing further mechanistic insights into lignin polymerization in vivo.

Bioactivation of 2-nitrofluorene to reactive intermediates that bind covalenty to DNA, RNA and protein in vitro and in vivo in the rat

1990 ◽  
Vol 11 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Frant C.J. Wierckx ◽  
Rinny Wedzinga ◽  
John H.N. Meerman ◽  
Gerard Mulder
Keyword(s):  
Reactive Intermediates

scholarly journals Ferrocifen Loaded Lipid Nanocapsules: A Promising Anticancer Medication against Multidrug Resistant Tumors

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2291
Author(s):  
Pierre Idlas ◽  
Elise Lepeltier ◽  
Gérard Jaouen ◽  
Catherine Passirani
Keyword(s):  
Cancer Cells ◽  
Organometallic Compounds ◽  
Multidrug Resistant ◽  
Quinone Methide ◽  
Chemotherapeutic Drugs ◽  
Lipid Nanocapsules ◽  
In Vivo Experiments ◽  
Hydrophobic Compounds

Resistance of cancer cells to current chemotherapeutic drugs has obliged the scientific community to seek innovative compounds. Ferrocifens, lipophilic organometallic compounds composed of a tamoxifen scaffold covalently bound to a ferrocene moiety, have shown very interesting antiproliferative, cytotoxic and immunologic effects. The formation of ferrocenyl quinone methide plays a crucial role in the multifaceted activity of ferrocifens. Lipid nanocapsules (LNCs), meanwhile, are nanoparticles obtained by a free organic solvent process. LNCs consist of an oily core surrounded by amphiphilic surfactants and are perfectly adapted to encapsulate these hydrophobic compounds. The different in vitro and in vivo experiments performed with this ferrocifen-loaded nanocarrier have revealed promising results in several multidrug-resistant cancer cell lines such as glioblastoma, breast cancer and metastatic melanoma, alone or in combination with other therapies. This review provides an exhaustive summary of the use of ferrocifen-loaded LNCs as a promising nanomedicine, outlining the ferrocifen mechanisms of action on cancer cells, the nanocarrier formulation process and the in vivo results obtained over the last two decades.

Generation of Reactive Intermediates from 2-Nitrofluorene that Bind Covalently to DNA, RNA and Protein in Vitro and in Vivo in the RAT

Nitroarenes ◽  
1990 ◽  
pp. 219-230 ◽  
Author(s):  
Gerard J. Mulder ◽  
Frank C. J. Wierckx ◽  
Rinny Wedzinga ◽  
John H. N. Meerman
Keyword(s):  
Reactive Intermediates

scholarly journals Characterization of reactive intermediates formation in dacomitinib metabolism and bioactivation pathways elucidation by LC-MS/MS: in vitro phase I metabolic investigation

RSC Advances ◽  
2018 ◽  
Vol 8 (68) ◽  
pp. 38733-38744 ◽  
Author(s):  
Mohamed W. Attwa ◽  
Adnan A. Kadi ◽  
Ali S. Abdelhameed
Keyword(s):  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Reactive Intermediates ◽  
First Line ◽  
Metabolic Investigation ◽  
Epidermal Growth ◽  
Egfr Tkis ◽  
Irreversible Tyrosine Kinase Inhibitor

Dacomitinib (DCB) is a second generation irreversible tyrosine kinase inhibitor (TKI) that is claimed to overcome the disadvantages of the resistance developed by the first line epidermal growth factor receptor (EGFR) TKIs.

scholarly journals A Hopeful Natural Product, Pristimerin, Induces Apoptosis, Cell Cycle Arrest, and Autophagy in Esophageal Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Peng Huang ◽  
Li-Ying Sun ◽  
Yan-Qiao Zhang
Keyword(s):  
Esophageal Cancer ◽  
Therapeutic Agent ◽  
Quinone Methide ◽  
Cycle Arrest ◽  
Digestive Diseases ◽  
Cancer Tumor ◽  
Esophageal Cancer Cells

Esophageal cancer is one of the most common malignant digestive diseases worldwide. Although many approaches have been established for the treatment of esophageal cancer, the survival outcome has not improved. Pristimerin is a quinone methide triterpenoid with anticancer, antiangiogenic, anti-inflammatory, and antiprotozoal activities. However, the role of pristimerin in cancers such as esophageal cancer is unclear. In this study, we investigated the role and mechanisms of action of pristimerin in esophageal cancer. First, we found that pristimerin can induce apoptosis in esophageal cancer in vivo and in vitro. CCK-8 and clonogenic assays showed that pristimerin decreased the growth of Eca109 cells. In addition, we found that pristimerin decreased the protein expression of CDK2, CDK4, cyclin E, and BCL-2 and increased the expression of CDKN1B. Meanwhile, pristimerin elevated the ratio of LC3-II/LC3-I. Otherwise, downregulation of CDKN1B can reduce the esophageal cancer tumor growth induced by pristimerin. In conclusion, our findings revealed an important role of pristimerin in esophageal cancer and suggest that pristimerin might be a potential therapeutic agent for this cancer.

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