Novel Glycyrrhetin Ureas Possessing 2-Hydroxy-3-enone A Ring: Modification, Anti-inflammatory Activity, and Targeted STING for the Remedy of Acute Kidney Injury.

Glycyrrhetin urea has emerged as a privileged scaffold with anti-inflammatory activity for the treatment and prevention of acute kidney injury (AKI). In this study, structural modifications of the A ring of glycyrrhetinic acid yielded a series of urea derivatives, among which compound exhibited the most promising anti-inflammatory activity. was confirmed to interact with STING through a cellular heat shift assay and to inhibit the STING/NF-κB pathway in RAW264.

Trolox derivatives: Synthesis, structure-activity relationship and promote wound healing by regulating oxidative stress and inflammation.

To find new antioxidants, 13 Trolox amides (2a-2m) and 7 Trolox esters (3a-3g) were synthesized and evaluated for their anti-inflammatory and antioxidant activity. Compounds 2e, 2i, 3b and 3d showed potent anti-inflammatory and antioxidant activity, amongst them, 3d demonstrated the most photoprotective effects on UVB-irradiated human skin keratinocyte (HaCaT) cells (IC = 5.13 µM) through efficiently scavenging free radicals and dose-dependently reducing reactive oxygen species (ROS) and apoptosis generation, as well as effectively promoting wound healing.

Structure-Tissue Exposure/Selectivity Relationship (STR) on Carbamates of Cannabidiol.

The structure-tissue exposure/selectivity relationship (STR) aids in lead optimization to improve drug candidate selection and balance clinical dose, efficacy, and toxicity. In this work, butyrocholinesterase (BuChE)-targeted cannabidiol (CBD) carbamates were used to study the STR in correlation with observed efficacy/toxicity. CBD carbamates with similar structures and same molecular target showed similar/different pharmacokinetics.

Natural phenol carbamates: Selective BuChE/FAAH dual inhibitors show neuroprotection in an Alzheimer's disease mouse model.

FAAH inhibition can indirectly enhance endocannabinoid signaling to therapeutic levels, effectively preventing or slowing its progression of Alzheimer's disease (AD). Hence, the search for effective dual FAAH/cholinesterase inhibitors is considerable need for disease-modifying therapies. To this aim, we designed, synthesized, and tested three series of natural phenol carbamates.

A new antibacterial with anti-inflammatory properties promotes wound healing through inhibiting cGAS/STING/NF-κB/IRF3 pathway.

Benzothiazole-urea hybrid 8l was found to be a potent anti-bacterial agent against methicillin-resistant Staphylococcus aureus (MRSA2858) (MIC = 0.78 μM, Eur J Med Chem. 2022,236:114333).

GAMG ameliorates silica-induced pulmonary inflammation and fibrosis via the regulation of EMT and NLRP3/TGF-β1/Smad signaling pathway.

Silicosis is an occupational disease caused by exposure to silica characterized by pulmonary inflammation and fibrosis, for which there is a lack of effective drugs. Glycyrrhetinic acid 3-O-β-D-glucuronide (GAMG) can treat silicosis due to its anti-inflammatory and anti-fibrotic properties. Here, the effect of therapeutic interventions of GAMG was evaluated in early-stage and advanced silicosis mouse models.

Cannabidiol suppresses silica-induced pulmonary inflammation and fibrosis through regulating NLRP3/TGF-β1/Smad2/3 pathway.

Silica-induced pulmonary fibrosis is an irreversible and progressive lung disease with limited treatments available. In this work, FDA-approved cannabidiol (CBD) was studied for its potential medical use in silicosis. In silicosis female C57BL/6 mice model, oral CBD or pirfenidone (PFD) on day 1 after intratracheal drip silica (150 mg/mL) and continued for 42 days.

Inhibiting Peptidoglycan Hydrolase Alleviates MRSA Pneumonia Through Autolysin-Mediated MDP-NOD2 Pathway.

Background: (MRSA) is a cause of staph infection that is difficult to treat because of resistance to some antibiotics. A recent study indicated that diarylurea is a novel antibacterial agent against multi-drug resistant . In this work, we refined the bactericidal mechanism of as a peptidoglycan (PG) hydrolase by affecting AtlA-mediated PG homeostasis.

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.

Transient Absorption Spectroscopic Investigation of the Photocyclization-Deprotection Reaction of 3',5'-Dimethoxybenzoin Fluoride.

The 3',5'-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization-deprotection reaction, resulting in a high yield of 3',5'-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased.

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.

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

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

Preoperative CT findings and prognosis of pulmonary sarcomatoid carcinoma: comparison with conventional NSCLC of similar tumor size.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) but differs in terms of treatment strategies compared with conventional-NSCLC (c-NSCLC). However, preoperative CT differentiation between PSC and c-NSCLC remains a challenge. This study aimed to explore the CT findings and prognosis of PSC compared with c-NSCLC of similar tumor size.

Microtiter plate-based chemistry and in situ screening: SuFEx-enabled lead discovery of selective AChE inhibitors.

Sulphur fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulphur connective hubs. Here, we reported an efficient synthesis and screening method for building a library of sulphonamides on the picomolar scale by SuFEx reaction between a sulphonyl fluoride (RSOF) core and primary or secondary amines. This biocompatible SuFEx reaction would allow us to rapidly synthesise sulphonamide molecules, and evaluate their ChE inhibitory activity.

A Review of the Antiviral Activities of Glycyrrhizic Acid, Glycyrrhetinic Acid and Glycyrrhetinic Acid Monoglucuronide.

Licorice, a natural medicine derived from the roots and rhizomes of species, possesses a wide range of therapeutic applications, including antiviral properties. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Glycyrrhetinic acid 3--mono-β-d-glucuronide (GAMG) is the active metabolite of GL.

Sulfur-fluoride exchange (SuFEx)-enabled lead discovery of AChE inhibitors by fragment linking strategies.

SuFEx click chemistry has been a method for the rapid synthesis of functional molecules with desirable properties. Here, we demonstrated a workflow that allows for in situ synthesis of sulfonamide inhibitors based on SuFEx reaction for high-throughput testing of their cholinesterase activity. According to fragment-based drug discovery (FBDD), sulfonyl fluorides [R-SOF] with moderate activity were identified as fragment hits, rapidly diversified into 102 analogs in SuFEx reactions, and the sulfonamides were directly screened to yield drug-like inhibitors with 70-fold higher potency (IC = 94 nM).

Time-Resolved Spectroscopic Study of a Photoinduced Intramolecular Chloride Exchange Reaction of 3',5'-Dimethoxybenzoin Chloride.

Photoremovable protecting groups are of great importance due to their remote control over the liberation of diverse reactive species temporally and spatially, including biologically active compounds and functional groups. Here, an in-depth investigation on the heterolysis-solvolysis reaction mechanisms of a photoremovable protecting group, 3',5'-dimethoxybenzoin (DMB) chloride, has been accomplished. With the aid of transient absorption and time-resolved resonance Raman spectroscopies, the features of the intermediates that emerged from the photolysis process were directly observed.

Efflux pump inhibitor combined with ofloxacin decreases MRSA biofilm formation by regulating the gene expression of NorA and quorum sensing.

Carbonyl cyanide -nitrophenylhydrazone (2e) displayed a lone or synergistic efficacy against MRSA (, 2020, 10, 17854). In this work, the synergistic mechanism of 2e with ofloxacin was studied. MRSA2858 had potential for biofilm formation, and the value of MBEC of 2e alone was 0.

Discovery of ()-2-Methoxyethene-1-sulfonyl Fluoride for the Construction of Enaminyl Sulfonyl Fluoride.

A new sulfonyl fluoride reagent ()-2-methoxyethene-1-sulfonyl fluoride (MeO-ESF) was developed and successfully applied for the construction of enaminyl sulfonyl fluoride (-ESF). This protocol provides highly atom-economical access to diverse -ESF and produces CHOH as the sole byproduct under mild and environmentally benign conditions.

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

() 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 . Diarylurea with benign drug-like property exhibited potent antibacterial and anti-biofilm activity through inhibiting the genes expression of NlpC/p60 hydrolase-secreted antigen A () and autolysins (), down-regulating the expression of biofilm adherence related genes aggregation substance (), enterococcal surface protein () against .

Effect of Perfluoropolymers on the Anti-Wear Properties of Carbon Fiber/Polyphenylene Sulfide Composites: A Comparative Study.

In this work, several perfluoropolymers (PFP), including commercial polytetrafluoroethylene (PTFE), perfluorinated ethylene-propylene copolymer (FEP), tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (PFA), and irradiated PTFE (iPTFE) were used as additives to lubricate carbon fiber (CF)-reinforced polyphenylene sulfide (PPS) composites. The tribological properties of the yielding composites were studied and correlated with the melt processability of PFPs. Although the neat FEP and PFA have higher friction coefficients when compared with neat PTFE, the composites filled with FEP and PFA additives were found to exhibit a lower friction coefficient compared to PTFE at PFP content below 10 wt %.

Fluorosulfate-containing pyrazole heterocycles as selective BuChE inhibitors: structure-activity relationship and biological evaluation for the treatment of Alzheimer's disease.

Novel scaffolds are expected to treat Alzheimer's disease, pyrazole-5-fluorosulfates were found as selective BuChE inhibitors. Compounds were assayed for ChE inhibitory activity, amongst them, compound showed potent BuChE and BuChE inhibition (IC = 0.79 μM and 6.

Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats.

To understand that 18β-Glycyrrhetic acid 3-O-mono--D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent (2377.

18β-Glycyrrhetinic acid monoglucuronide (GAMG) alleviates single-walled carbon nanotubes (SWCNT)-induced lung inflammation and fibrosis in mice through PI3K/AKT/NF-κB signaling pathway.

Carbon nanotubes (CNTs) have become far and wide used in a number of technical and merchant applications as a result of substantial advances in nanotechnology, therein single-walled carbon nanotubes (SWCNT) are one of the most promising nanoparticles. Inhaling CNTs has been linked to a variety of health problems, including lung fibrosis. Glycyrrhetinic acid 3-O-mono-β-D-glucuronide (GAMG), a natural sweetener, has anti-inflammatory and antioxidant capacities.

Novel benzothiazole‒urea hybrids: Design, synthesis and biological activity as potent anti-bacterial agents against MRSA.

Novel benzothiazole‒urea hybrids were designed, synthesized and evaluated their anti-bacterial activity. They only exhibited anti-bacterial activity against Gram-positive bacteria, including clinical methicillin-resistant S. aureus (MRSA), compounds 5f, 5i, 8e, 8k and 8l exhibited potent activity (MIC = 0.