4-phenylpyridin-2-yl-guanidine (5b): a new inhibitor of the overproduction of pro-inflammatory cytokines (TNFα and Il1β) was identified from a high-throughput screening of a chemical library on human peripheral blood mononuclear cells (PBMCs) after LPS stimulation. Derivatives, homologues and rigid mimetics of 5b were designed and synthesized, and their cytotoxicity and ability to inhibit TNFα overproduction were evaluated. Among them, compound 5b and its mimetic 12 (2-aminodihydroquinazoline) showed similar inhibitory activities, and were evaluated in vivo in models of lung inflammation and neuropathic pain in mice. In particular, compound 12 proved to be active (5 mg/kg, ip) in both models.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2018.01.049 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Supramolecular multiplexes from collagen mimetic peptide-PNA(GGG) conjugates and C-rich DNA: pH-induced reversible switching from triplex-duplex to triplex--motif.
Biomater Sci
December 2024
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Tirupati, Karkambadi Road, Mangalam, Tirupati 517507, India.
Peptides are well known for forming nanoparticles, while DNA duplexes, triplexes and tetraplexes create rigid nanostructures. Accordingly, the covalent conjugation of peptides to DNA/RNA produces hybrid self-assembling features and may lead to interesting nano-assemblies distinct from those of their individual components. Herein, we report the preparation of a collagen mimetic peptide incorporating lysine in its backbone, with alkylamino side chains radially conjugated with G-rich PNA [collagen-(PNA-GGG)].
View Article and Find Full Text PDFInfluence of Trp-Cage on the Function and Stability of GLP-1R Agonist Exenatide Derivatives.
J Med Chem
September 2024
Medicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, H-1117Budapest, Hungary.
Article Synopsis
- Exenatide (Ex4) is a peptide used to treat diabetes and obesity, and its effectiveness is influenced by a structural feature called the Trp-cage (Tc) motif.
- The study investigates how different versions of Ex4 with modified Tc motifs affect thermal stability, aggregation, insulin secretion, and binding to the GLP-1 receptor (GLP-1R).
- Findings indicate that while stronger Tc motifs increase resistance to instability and aggregation, they can negatively impact the bioactivity of Ex4 by interfering with key interactions needed for effective signaling in the GLP-1R.
Simultaneous Color- and Dose-Controlled Thiol-Ene Resins for Multimodulus 3D Printing with Programmable Interfacial Gradients.
Adv Mater
October 2024
Department of Chemistry, The University of Texas at Austin, Austin, TX, 78712, USA.
Drawing inspiration from nature's own intricate designs, synthetic multimaterial structures have the potential to offer properties and functionality that exceed those of the individual components. However, several contemporary hurdles, from a lack of efficient chemistries to processing constraints, preclude the rapid and precise manufacturing of such materials. Herein, the development of a photocurable resin comprising color-selective initiators is reported, triggering disparate polymerization mechanisms between acrylate and thiol functionality.
View Article and Find Full Text PDFSynthesis of a Phosphoethanolamine Cellulose Mimetic and Evaluation of Its Unanticipated Biofilm Modulating Properties.
ACS Infect Dis
September 2024
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
When coordinating and adhering to a surface, microorganisms produce a biofilm matrix consisting of extracellular DNA, lipids, proteins, and polysaccharides that are intrinsic to the survival of bacterial communities. Indeed, bacteria produce a variety of structurally diverse polysaccharides that play integral roles in the emergence and maintenance of biofilms by providing structural rigidity, adhesion, and protection from environmental stressors. While the roles that polysaccharides play in biofilm dynamics have been described for several bacterial species, the difficulty in isolating homogeneous material has resulted in few structures being elucidated.
View Article and Find Full Text PDFMatrix stiffness-dependent regulation of immunomodulatory genes in human MSCs is associated with the lncRNA CYTOR.
Proc Natl Acad Sci U S A
August 2024
Donnelly Centre, University of Toronto, Toronto, ON M5S3E1, Canada.
Cell-matrix interactions in 3D environments significantly differ from those in 2D cultures. As such, mechanisms of mechanotransduction in 2D cultures are not necessarily applicable to cell-encapsulating hydrogels that resemble features of tissue architecture. Accordingly, the characterization of molecular pathways in 3D matrices is expected to uncover insights into how cells respond to their mechanical environment in physiological contexts, and potentially also inform hydrogel-based strategies in cell therapies.
View Article and Find Full Text PDFWant 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!