When exposed to electrophiles, human colorectal cancer cells (HCT116) counteract oxidative stress through activating NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. To identify new activators, luciferase reporter gene assay was used to screen in-house database of our laboratory, leading to a novel α-pyrone compound 1 as a hit. 2 with 2-fluoro phenyl group exhibited the strongest ARE inductive activity in the first round structure-activity relationship (SAR) study. Biological studies showed the compound induced nuclear translocation of Nrf2 preceded by phosphorylation of ERK1/2. The data encouraged us to use 2 as lead and 20 derivatives were synthesized to discuss a more detailed SAR, leading to a more potent compound 9, which can be the starting compound for further modification.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2013.06.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development of Thermosensitive Hydrogels with Tailor-Made Geometries to Modulate Cell Harvesting of Non-Flat Cell Cultures.
Gels
December 2024
Polymer Functionalization Group, Departamento de Química Macromolecular Aplicada, Instituto de Ciencia y Tecnología de Polímeros-Consejo Superior de Investigaciones Científicas (ICTP-CSIC), Calle Juan de la Cierva, n° 3, 28006 Madrid, Spain.
Considering the complexity in terms of design that characterizes the different tissues of the human body, it is necessary to study and develop more precise therapies. In this sense, this article presents the possibility of fabricating photocurable thermosensitive hydrogels with free geometry and based on N-Vinyl Caprolactam (VCL) with the aim of modulating the adhesion of non-planar cell cultures. The fabrication process is based on the use as a mold of two-layer thick water-soluble polyvinyl alcohol (PVA) previously printed by Extrusion Material (MatEx).
View Article and Find Full Text PDF6-aryloxy-2-aminopyrimidine-benzonitrile hybrids as anti-infective agents: Synthesis, bioevaluation, and molecular docking.
Arch Pharm (Weinheim)
January 2025
Fluoro & Agro Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, India.
This report explores the potential of novel 6-aryloxy-2-aminopyrimidine-benzonitrile scaffolds as promising anti-infective agents in the face of the increasing threat of infectious diseases. Starting from 2-amino-4,6-dichloropyrimidine, a series of 24 compounds inspired from the antiviral drugs dapivirine, etravirine, and rilpivirine were designed and synthesized via a two-step reaction sequence in good yields. Biological testing of synthetic analogs revealed potent inhibition against both viral and tuberculosis targets.
View Article and Find Full Text PDFSynthesis and bioevaluation of a new Ga-labelled niraparib derivative that targets PARP-1 for tumour imaging.
Bioorg Chem
December 2024
Key Laboratory of Radiopharmaceuticals of the Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), College of Chemistry, Beijing Normal University, Beijing 100875, China. Electronic address:
Poly ADP-ribose polymerase (PARP) inhibitors prevent the repair of DNA single-strand breaks in cancer cells with abnormal homologous recombination, producing a synthetic lethal effect. Thus, PARP inhibitors have become clinically effective anticancer drugs. Labelling with radionuclides may extend the use of PARP inhibitors as tracers in nuclear medicine diagnostics, helping to stratify patients.
View Article and Find Full Text PDFSynthesis, and bio-evaluation studies of new isothiocyanate derivatives with respect to COX inhibition and HS release profiles.
RSC Med Chem
October 2024
Department of Molecular Biology and Genetics, Faculty of Science, Canakkale Onsekiz Mart University Canakkale Türkiye
The development of HS-donating derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) is considered important to reduce or overcome their gastrointestinal side effects. Sulforaphane, one of the most extensively studied isothiocyanates (ITCs), effectively releases HS at a slow rate. Thus, we rationally designed, synthesized, and characterized new ITC derivatives (I1-3 and I1a-e) inspired by the natural compound sulforaphane.
View Article and Find Full Text PDFComputational Design, Synthesis, and Bioevaluation of 2-(Pyrimidin-4-yl) oxazole-4-carboxamide Derivatives: Dual Inhibition of EGFR and EGFR with ADMET Profiling.
Bioorg Chem
December 2024
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!