cyclic-gmp has been researched along with quinoline* in 3 studies
3 other study(ies) available for cyclic-gmp and quinoline
| Article | Year |
|---|---|
Design and Synthesis of Novel c-di-GMP G-Quadruplex Inducers as Bacterial Biofilm Inhibitors.
The formation of biofilms by clinical pathogens typically leads to chronic and recurring antibiotic-resistant infections. High cellular levels of cyclic diguanylate (c-di-GMP), a ubiquitous secondary messenger of bacteria, have been proven to be associated with a sessile biofilm lifestyle of pathogens. A promising antibiofilm strategy involving the induction of c-di-GMP to form dysfunctional G-quadruplexes, thereby blocking the c-di-GMP-mediated biofilm regulatory pathway, was proposed in this study. In this new strategy, a series of novel c-di-GMP G-quadruplex inducers were designed and synthesized for development of therapeutic biofilm inhibitors. Compound Topics: Anti-Bacterial Agents; Benzothiazoles; Biofilms; Cyclic GMP; Dose-Response Relationship, Drug; Drug Design; G-Quadruplexes; Microbial Sensitivity Tests; Molecular Structure; Pseudomonas aeruginosa; Quinolines; Structure-Activity Relationship | 2021 |
Structural Analyses of Toll-like Receptor 7 Reveal Detailed RNA Sequence Specificity and Recognition Mechanism of Agonistic Ligands.
Toll-like receptor 7 (TLR7) is an innate immune receptor for single-stranded RNA (ssRNA) and has important roles in infectious diseases. We previously reported that TLR7 shows synergistic activation in response to two ligands, guanosine and ssRNA. However, the specific ssRNA sequence preference, detailed recognition mode of TLR7 and its ligand, and molecular determinants of TLR7 and TLR8 selectivity remain unknown. Here, we report on TLR7 from a large-scale crystallographic study combined with a multifaceted approach. We reveal that successive uridine-containing ssRNAs fully or moderately bind TLR7, whereas single uridine-containing ssRNAs have reduced affinities. We also reveal the detailed relationships between the chemical structures of ligands and their binding to TLR7. We demonstrate that an engineered TLR8 mutant alters its responsiveness to TLR7-specific ligands. Finally, we identify guanosine 2',3'-cyclic phosphate (2',3'-cGMP) as a possible endogenous ligand for TLR7 with greater affinity than guanosine. The abundant structural information will facilitate future development of treatments targeting TLR7. Topics: Amino Acid Sequence; Animals; Base Sequence; Cyclic GMP; Drosophila; HEK293 Cells; Humans; Ligands; Models, Molecular; Mutagenesis; Protein Binding; Quinolines; RNA; Structure-Activity Relationship; Toll-Like Receptor 7; Toll-Like Receptor 8 | 2018 |
Identification of a Novel 1,2,3,4-Tetrahydrobenzo[b][1,6]naphthyridine Analogue as a Potent Phosphodiesterase 5 Inhibitor with Improved Aqueous Solubility for the Treatment of Alzheimer's Disease.
Phosphodiesterase 5 (PDE5) hydrolyzes cyclic guanosine monophosphate (cGMP) leading to increased levels of the cAMP response element binding protein (CREB), a transcriptional factor involved with learning and memory processes. We previously reported potent quinoline-based PDE5 inhibitors (PDE5Is) for the treatment of Alzheimer's disease (AD). However, the low aqueous solubility rendered them undesirable drug candidates. Here we report a series of novel PDE5Is with two new scaffolds, 1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridine and 2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-one. Among them, compound 6c, 2-acetyl-10-((3-chloro-4-methoxybenzyl)amino)-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridine-8-carbonitrile, the most potent compound, has an excellent in vitro IC Topics: Alzheimer Disease; Animals; Binding Sites; Cyclic AMP Response Element-Binding Protein; Cyclic GMP; Humans; Mice; Molecular Docking Simulation; Naphthyridines; Phosphodiesterase 5 Inhibitors; Quinolines; Solubility; Structure-Activity Relationship | 2017 |