Construction of a Sensitive Fluorescence Sensor for Convenient 1‑HP and UA Detection Relied on a Stable Eu-MOF

Herein, a new three-dimensional Eu-MOF, [Me2NH2]2­[Eu3(mtptc)2­(CH3COO)3]·DMA·H2O (1), has been elaborately prepared through the reaction of europium nitrate and a symmetric tetra-carboxylate ligand, 5′-methyl-[1,1′:3′,1″-triphenyl]-3,3″,5,5″-tetracarboxylic acid (H4mtptc). Noteworthily, compound 1 represents marked stability covering acid–base stability in the pH range of 2–14, thermal stability maintaining skeleton integrity when heated at 350 °C, solvent stability in some common solvents, and air stability in open air more than 4 weeks characterized by powder X-ray diffraction (XRD) and temperature-dependent powder XRD analyses. Remarkably, luminescent sensing measurements manifest that compound 1 is deemed as a hopeful fluorescent probe for rapid recognition of 1-hydroxypyrene (1-HP) and uric acid (UA) equipped with excellent sensitivity with a quenching efficiency of 99.1% for 1-HP and 97.4% for UA. Besides, the luminescent sensing performance of compound 1 toward 1-HP and UA possesses super stability in dimethylformamide/H2O solution, N-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid buffer solution, and human urine

In Vitro Pharmacokinetic Optimizations of AM2-S31N Channel Blockers Led to the Discovery of Slow-Binding Inhibitors with Potent Antiviral Activity against Drug-Resistant Influenza A Viruses

Influenza viruses are respiratory pathogens that are responsible for both seasonal influenza epidemics and occasional influenza pandemics. The narrow therapeutic window of oseltamivir, coupled with the emergence of drug resistance, calls for the next-generation of antivirals. With our continuous interest in developing AM2-S31N inhibitors as oral influenza antivirals, we report here the progress of optimizing the in vitro pharmacokinetic (PK) properties of AM2-S31N inhibitors. Several AM2-S31N inhibitors, including compound <b>10b</b>, were discovered to have potent channel blockage, single to submicromolar antiviral activity, and favorable in vitro PK properties. The antiviral efficacy of compound <b>10b</b> was also synergistic with oseltamivir carboxylate. Interestingly, binding kinetic studies (<i>K</i>_d, <i>K</i>_on, and <i>K</i>_off) revealed several AM2-S31N inhibitors that have similar <i>K</i>_d values but significantly different <i>K</i>_on and <i>K</i>_off values. Overall, this study identified a potent lead compound (<b>10b</b>) with improved in vitro PK properties that is suitable for the in vivo mouse model studies