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IARC Monographs on the Evaluation of... 1999
Topics: Animals; Aziridines; Carcinogenicity Tests; Carcinogens; Humans; Kidney; Mutagenicity Tests; Mutagens; Salmonella typhimurium
PubMed: 10476433
DOI: No ID Found -
British Medical Journal Jun 1952
Topics: Triethylenemelamine
PubMed: 14935258
DOI: No ID Found -
Expert Opinion on Drug Metabolism &... Jul 2017Apaziquone (also known as EO9 and Qapzola) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill... (Review)
Review
Apaziquone (also known as EO9 and Qapzola) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill aerobic and/or hypoxic cancer cells. Areas covered: Whilst its poor pharmacokinetic properties contributed to its failure in phase II clinical trials when administered intravenously, these properties were ideal for loco-regional therapies. Apaziquone demonstrated good anti-cancer activity against non-muscle invasive bladder cancer (NMIBC) when administered intravesically to marker lesions and was well tolerated with no systemic side effects. However, phase III clinical trials did not reach statistical significance for the primary endpoint of 2-year recurrence in apaziquone over placebo although improvements were observed. Post-hoc analysis of the combined study data did indicate a significant benefit for patients treated with apaziquone, especially when the instillation of apaziquone was given 30 min or more after surgery. A further phase III study is ongoing to test the hypotheses generated in the unsuccessful phase III studies conducted to date. Expert opinion: Because of its specific pharmacological properties, Apaziquone is excellently suited for local therapy such as NMIBC. Future studies should include proper biomarkers.
Topics: Administration, Intravesical; Animals; Antineoplastic Agents; Aziridines; Humans; Indolequinones; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms
PubMed: 28637373
DOI: 10.1080/17425255.2017.1341490 -
Molecules (Basel, Switzerland) Dec 2022A type of MCM-41 supported dicationic imidazolium ionic liquid nanocatalyst has been synthesized and found to be competent for the synthesis of 2-oxazolidinones through...
Novel MCM-41 Supported Dicationic Imidazolium Ionic Liquids Catalyzed Greener and Efficient Regioselective Synthesis of 2-Oxazolidinones from Aziridines and Carbon Dioxide.
A type of MCM-41 supported dicationic imidazolium ionic liquid nanocatalyst has been synthesized and found to be competent for the synthesis of 2-oxazolidinones through the sustainable chemical conversion of CO with aziridines. It was shown that the highest efficiency was achieved in the cycloaddition of a series of aziridines and CO in the presence of a catalytic amount of the solid catalyst MCM-41@ILLaCl under mild conditions. Merits of this meticulously designed protocol are the use of a novel supported ionic liquid catalyst, the easy work-up process, good to excellent yields, a short reaction time, and purification without column chromatography. Overall, the present protocol of synthesizing 2-oxazolidinones under cocatalyst- and solvent-free conditions using MCM-41@ILLaCl is promising for industrial applications.
Topics: Carbon Dioxide; Ionic Liquids; Oxazolidinones; Aziridines; Catalysis
PubMed: 36615437
DOI: 10.3390/molecules28010242 -
Transplantation and Cellular Therapy Mar 2023Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical...
Impact of Conditioning Regimen and Graft-versus-Host Disease Prophylaxis on The Outcome of Haploidentical Peripheral Blood Stem Cell Transplantation for High-Risk Severe Aplastic Anemia in Children and Young Adults: A Report from the Pediatric Severe Aplastic Anemia Consortium of India.
Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical family donors (HFDs) have improved, making it a feasible option for patients lacking an HLA-identical donor. However, data on HFD-HCT for younger patients with SAA is sparse. In this multicenter retrospective study, we evaluated the outcomes of 79 patients undergoing HFD-HCT for SAA. All the patients were heavily pretransfused, the median time to HCT was >12 months, and 67% had failed previous therapies. Conditioning was based on fludarabine (Flu)-cyclophosphamide (Cy)-antithymocyte globulin (ATG)/total body irradiation (TBI) with or without thiotepa/melphalan (TT/Mel). Post-transplantation Cy (PTCy) and calcineurin inhibitors (CNIs)/sirolimus were used as graft-versus-host disease (GVHD) prophylaxis with or without abatacept. The rate of primary graft failure (PGF) was 16.43% overall, lower in patients conditioned with TT/Mel. The incidences of acute and chronic GVHD were 26.4% and 18.9%, respectively. At a median follow-up of 48 months, the overall survival (OS) and event-free survival (EFS) were 61.6% and 58.1%, respectively. Both OS and EFS were better in the TT/Mel recipients and with abatacept as GVHD prophylaxis. On multivariate analysis, the use of abatacept was found to favorably impact the outcome variables, including GVHD and EFS. Our study suggests that PTCy-based HFD-HCT is a reasonable option for young patients with high-risk SAA, in whom optimization of conditioning and GVHD prophylaxis might further improve outcomes.
Topics: Humans; Child; Young Adult; Peripheral Blood Stem Cell Transplantation; Anemia, Aplastic; Abatacept; Retrospective Studies; Cyclophosphamide; Graft vs Host Disease; Thiotepa
PubMed: 36572385
DOI: 10.1016/j.jtct.2022.12.010 -
Angewandte Chemie (International Ed. in... Aug 2017A Rh -catalyzed direct and stereospecific N-H- and N-alkyl aziridination of olefins is reported that uses hydroxylamine-O-sulfonic acids as inexpensive, readily...
A Rh -catalyzed direct and stereospecific N-H- and N-alkyl aziridination of olefins is reported that uses hydroxylamine-O-sulfonic acids as inexpensive, readily available, and nitro group-free aminating reagents. Unactivated olefins, featuring a wide range of functional groups, are converted into the corresponding N-H or N-alkyl aziridines in good to excellent yields. This operationally simple, scalable transformation proceeds efficiently at ambient temperature and is tolerant towards oxygen and trace moisture.
Topics: Alkenes; Aziridines; Catalysis; Hydroxylamines; Molecular Structure; Rhodium; Stereoisomerism
PubMed: 28614619
DOI: 10.1002/anie.201705530 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2018Cyclophellitol aziridines are potent irreversible inhibitors of retaining glycosidases and versatile intermediates in the synthesis of activity-based glycosidase probes...
Cyclophellitol aziridines are potent irreversible inhibitors of retaining glycosidases and versatile intermediates in the synthesis of activity-based glycosidase probes (ABPs). Direct 3-amino-2-(trifluoromethyl)quinazolin-4(3H)-one-mediated aziridination of l-ido-configured cyclohexene has enabled the synthesis of new covalent inhibitors and ABPs of α-l-iduronidase, deficiency of which underlies the lysosomal storage disorder mucopolysaccharidosis type I (MPS I). The iduronidase ABPs react covalently and irreversibly in an activity-based manner with human recombinant α-l-iduronidase (rIDUA, Aldurazyme ). The structures of IDUA when complexed with the inhibitors in a non-covalent transition state mimicking form and a covalent enzyme-bound form provide insights into its conformational itinerary. Inhibitors 1-3 adopt a half-chair conformation in solution ( H and H ), as predicted by DFT calculations, which is different from the conformation of the Michaelis complex observed by crystallographic studies. Consequently, 1-3 may need to overcome an energy barrier in order to switch from the H conformation to the transition state ( B) binding conformation before reacting and adopting a covalent S conformation. rIDUA can be labeled with fluorescent Cy5 ABP 2, which allows monitoring of the delivery of therapeutic recombinant enzyme to lysosomes, as is intended in enzyme replacement therapy for the treatment of MPS I patients.
Topics: Aziridines; Chromatography, Liquid; Cyclohexanols; Enzyme Assays; Enzyme Inhibitors; Fluorescent Dyes; Humans; Iduronidase; Microscopy, Fluorescence; Models, Molecular; Recombinant Proteins; Staining and Labeling; Tandem Mass Spectrometry
PubMed: 30307091
DOI: 10.1002/chem.201804662 -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Aziridines; Carcinogenicity Tests; Carcinogens, Environmental; Environmental Exposure; Government Regulation; Guidelines as Topic; Humans; Molecular Structure; Occupational Exposure; Rats
PubMed: 21860477
DOI: No ID Found -
Synapse (New York, N.Y.) Jun 2019Cancer survivorship has increased greatly as therapies have become more advanced and effective. Thus, we must now focus on improving the quality of life of patients...
Cancer survivorship has increased greatly as therapies have become more advanced and effective. Thus, we must now focus on improving the quality of life of patients after treatment. After chemotherapy, many patients experience chemotherapy-induced cognitive decline, indicating a need to investigate pathologies associated with this condition. In this study, we addressed cognitive impairment after thioTEPA treatment by assessing behavior and assaying cytokine production and the structure of dendrites in the hippocampus. Male mice were given three intraperitoneal injections of thioTEPA. Five weeks later, the mice underwent behavior testing, and brains were collected for Golgi staining and cytokine analysis. Behavior tests included y-maze and Morris water maze and licking behavioral task. Cytokines measured include: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-10, IL-12p70, MCP-1, TNF-α, GMCSF, and RANTES. We observed decreased memory retention in behavioral tasks. Also, dendritic arborization and length were decreased after chemotherapy treatment. Finally, thioTEPA decreased cytokine production in animals treated with chemotherapy, compared to saline-treated controls. Here, we used a mouse model to correlate the decreases in dendritic complexity and inflammatory cytokine production with cognitive impairment after chemotherapy.
Topics: Animals; Antineoplastic Agents, Alkylating; Brain; Cognition; Cognitive Dysfunction; Cytokines; Injections, Intraperitoneal; Male; Maze Learning; Mice; Mice, Inbred C57BL; Movement; Thiotepa
PubMed: 30586195
DOI: 10.1002/syn.22085 -
Journal of the American Chemical Society Apr 2018The stereoselective synthesis of syn-β-fluoroaziridine building blocks via chiral aryl iodide-catalyzed fluorination of allylic amines is reported. The method employs...
The stereoselective synthesis of syn-β-fluoroaziridine building blocks via chiral aryl iodide-catalyzed fluorination of allylic amines is reported. The method employs HF-pyridine as a nucleophilic fluoride source together with mCPBA as a stoichiometric oxidant, and affords access to arylethylamine derivatives featuring fluorine-containing stereocenters in high diastereo- and enantioselectivity. Catalyst-controlled diastereoselectivity in the fluorination of chiral allylic amines enabled the preparation of highly enantioenriched 1,3-difluoro-2-amines bearing three contiguous stereocenters. The enantioselective catalytic method was applied successfully to other classes of multifunctional alkene substrates to afford anti-β-fluoropyrrolidines, as well as a variety of 1,2-oxyfluorinated products.
Topics: Alkenes; Amination; Amines; Aziridines; Catalysis; Hydrocarbons, Iodinated; Molecular Structure; Stereoisomerism
PubMed: 29583001
DOI: 10.1021/jacs.8b02143