Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F- and HClO in Organisms.

Fluoride anions (F-) play a crucial role in human physiological processes. However, excessive intake of F- would affect oxygen metabolism and promote the generation of oxygen-free radicals. Hence, it is essential to develop a precise and efficient fluorescent probe for visualizing F--induced oxidative stress. In this work, we developed the first bifunctional BODIPY-based fluorescent probe dfBDP with p-tert-butyldimethylsilanolate benzyl thioether as the sensing site for the detection of F- and HClO via two distinct reactions, the self-immolative removal and the thioether oxidation, which generate the sensing products with two nonoverlap fluorescence bands: 800-1200 and 500-750 nm, respectively. The probe dfBDP displays rapid response, high specificity, and sensitivity for the detection of F- (LOD, 316.2 nM) and HClO (LOD, 33.9 nM) in vitro. Cellular imaging reveals a correlation between F--induced oxidative stress and the upregulation of HClO. Finally, probe dfBDP was employed to detect F- and HClO in mice under the stimulation of F-. The experimental results display that the level of HClO elevates in the liver of mice.

Arylacryl amides: Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF-κB pathway.

Arylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK2 cells. Furthermore, 9d can interact with TLR4 to inhibit TLR4/STING/NF-κB pathway in the RAW264.7 cell. In vivo AKI mice model, 9d significantly downregulated the level of serum creatinine (Scr), blood urea nitrogen (BUN) and the inflammatory factors (IL-1ß, IL-6, TNF-α) to improve kidney function. Morphological and KIM-1 analyses showed that 9d alleviated cisplatin-induced tubular damage. In a word, 9d was a promising lead compound for preventive and therapeutic of AKI.

A BODIPY-based fluorescent probe for simultaneous detection of H2O2 and viscosity during the pyroptosis process.

A dual functional BODIPY fluorescent probe was developed for simultaneous detection of H2O2 and viscosity, by collecting fluorescence from 800-1100 nm and 550-750 nm, respectively. Bioimaging based on the probe shows that H2O2 accumulates and cytoplasmic viscosity increases during the palmitic acid (PA)-induced pyroptosis process.

Antibacterial and anti-biofilm activity of diarylureas against Enterococcus faecium by suppressing the gene expression of peptidoglycan hydrolases and adherence.

Enterococcus faecium (E. faecium) is a clinical multidrug-resistant pathogen causing life-threatening infection, which makes it important to discover antibacterial agents with novel scaffolds and unique mechanism. In this study, the diarylurea scaffold was found to have potent antibacterial effect on E. faecium. Diarylurea ZJ-2 with benign drug-like property exhibited potent antibacterial and anti-biofilm activity through inhibiting the genes expression of NlpC/p60 hydrolase-secreted antigen A (sagA) and autolysins (atlA), down-regulating the expression of biofilm adherence related genes aggregation substance (agg), enterococcal surface protein (esp) against E. faecium. Moreover, ZJ-2 can be docked into SagA to inhibit daughter cell separation. In a mouse model of abdominal infection, ZJ-2 decreased the bacterial load and the level of IL-6 and TNF-α in a time-dependent manner. Overall, these findings indicated that diarylurea ZJ-2 has the potential to be developed as a therapeutic agent to treat drug-resistant enterococci and biofilm-related infections.