Search Results (974)

Herein, starting from (R)-(+)-α-methylbenzylamine, we report an efficient synthesis and full characterization of a new (R)-3-(1-hydroxyethylidene)-1-(1-phenylethyl)piperidine-2,4-dione, a new tetramic acid analog. The key steps involved a non-classical Corey–Chaykovsky intramolecular cyclization reaction to access the corresponding zwitterion, followed by a sequential desulfurization/reduction and condensation procedure. The titled product was obtained in five steps, and the desired product 7 with an overall 58% yield. Full article

Aryl halides are important intermediates for chemical synthesis. However, the negative reduction potential up to −2.7 V (vs. SCE) makes photoredox conversion of aryl halides by reductive dehalogenation to aryl radicals for chemical transformations difficult. Inspired by the outstanding photophysical properties of deazaflavin and triphenylamine, as well as results of theoretical calculations, we attached the diphenylamino group to C8 of deazaflavin, and the resulting compounds look fabricated by “fusing” deazaflavin and triphenylamine (TPA) together by sharing the benzene ring. We also introduced alkyl and aryl moieties to C5 and afforded a series of deazaflavin derivatives (dFLs), namely 10-butyl-8-(diphenylamino)-3,5-dimethylpyrimido[4,5b]quinoline-2,4(3H,10H)-dione (TPAdFlMe), 10-butyl-8-(diphenylamino)-3-methyl-5-(trifluoromethyl)pyrimido[4,5-b]quinoline-2,4(3H,10H)-dione(TPAdFlTF) and 10-butyl-8-(diphenylamino)-3-methyl-5-phenylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TPAdFlPh), and investigated their photophysical properties and performance as sensitizers in the photodehalogenation of aryl halides. We showed that the photophysical properties are significantly improved in these dFLs. The absorption bands of dFLs are redshifted and the absorbance is more than double that of riboflavin tetraacetate (RFTA). The singlet oxygen quantum yields of TPAdFlMe, TPAdFlTF and TPAdFlPh are 0.42, 0.25 and 0.39, respectively, and the corresponding redox potentials are −1.75, −0.75 and −1.71 V vs. Ag/Ag⁺, respectively, comparable to known deazaflavin-based sensitizers. Originating from these properties, TPAdFlMe and TPAdFlPh are capable of sensitizing the full photodehalogenation of 0.038 mmol p-iodoanisole, and the yields of the photodehalogenation of 0.038 mmol p-bromoanisole are 67 and 69%, respectively. They also demonstrate exceptional performance in the photodehalogenation of halides of polycyclic aromatics with yields in the range of 73% for 1-benzhydryl-3-bromobenzene to 100% for 1-bromonapthalene in 18 h runs. The performance of TPAdFlMe and TPAdFlPh in photodehalogenation are already comparable to recently reported deazaflavin-based sensitizers, and we propose the transformation would proceed though the consecutive photo-induced electron transfer (conPET) mechanism with consecutive excitation of charged deazaflavin-based radicals under light irradiation as the key step to generating the aryl radicals, and the vital role of sensitizer-based radicals is further confirmed by mechanistic investigations. We expect the findings will help to design novel flavin-based triplet sensitizers for photoredox catalytic organic transformations. Full article

N-Alkyl urazoles are important heterocyclic compounds that serve as important precursors to potent N-alkyl 1,2,4-triazoline-3,5-dione electrophiles. Traditional methods for urazole synthesis rely upon the use of toxic isocyanates. We have modified and optimized an overlooked and poorly described method from the literature for the synthesis of urazoles that now avoids the use of isocyanates, limits the use of solvents, and provides urazoles without the need for purification steps. A variety of urazoles are afforded in good to high yields. Full article

Sargassum is a widespread brown seaweed species and a source of bioactive compounds with promising antioxidant potential. Unfortunately, to date, the Sargassum species remains largely unexplored. This study was conducted to explore the bioactive compounds from Sargassum ilicifolium extracts collected from Nguyahan and Sundak Beaches, Gunungkidul, Indonesia, by observing Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS)-based metabolomics profiling and antioxidant activity assays. Metabolomic analysis detected 506 molecular features across different extraction methods and solvents, with five metabolites putatively dereplicated, including atractylenolide III, pheophorbide A, 13-docosenamide, 1,3,6,8-tetrahydroxy-2-(1-hydroxyhexyl)anthracene-9,10-dione, and 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid. Extraction parameters, particularly solvent polarity and sample pretreatment, have been shown to affect the metabolite variation. Dried samples showed less variation in metabolites than the fresh sample. Antioxidant activity assay showed a moderate to high radical scavenging activity (30–100%), with methanol extracts as a polar solvent inhibited more than semipolar solvents. This study provides a metabolomics-guided assessment of the antioxidant potential of S. ilicifolium, supporting its value and potential as a source of bioactive compounds for future pharmaceutical and nutraceutical applications. Full article

In this study, a metal-free approach was developed for the synthesis of isocoumarin frameworks by exploiting the reactivity between ortho-carboxylate-ester-substituted diaryliodonium salts and acetoacetates. This transformation involved the sequential C-arylation of an activated methylene substrate, followed by in situ enolization and intramolecular lactonization to construct an isocoumarin core. Under operationally simple conditions, a range of diaryliodonium salts and acetoacetate esters were employed to afford structurally diverse isocoumarins. The resulting products contained synthetically valuable functional groups, including halogen, nitro, carboxylate ester, and azide substituents, which facilitated further derivatization and extension toward complex architectures and potential applications. Subsequent transformation of the selected isocoumarin products enabled the synthesis of furo[3,4-c]isochromene-1,5-dione motifs, which are observed in several natural products. Full article

Background: Dental adhesive materials are important for achieving adequate adhesion results; however, they are not the only factor contributing to final bond strength, as improper operatory field isolation and contamination also significantly influence clinical outcomes. Objectives: This narrative review aims to provide a clinical perspective, supported by evidence-based arguments, to identify clinical procedures for optimizing adhesive protocols, including the execution of absolute isolation with a rubber dam, appropriate cleaning and preparation of the dental substrate, and protocols applicable to total-etch and self-etch techniques. Methods: The literature included in this review was selected through a structured search in PubMed, Scopus, and Web of Science, prioritizing systematic reviews, meta-analyses, long-term clinical studies, and foundational experimental investigations related to adhesive systems and substrate management. Results: A well-established clinical protocol that integrates proper adhesive selection, contamination-free operative field control, and adequate substrate preparation is essential for achieving predictable outcomes in adhesive dentistry. Conclusions: Although simplified adhesive systems offer acceptable bond strength results, established techniques continue to demonstrate consistent reliability, contributing to restorative longevity. Full article

Quinoline-2,4-dione derivatives represent an essential class of heterocycle scaffolds that have demonstrated wide applications in modern drug discovery. However, the efficient construction of 3,3-difluoro-quinoline-2,4-diones with broad substrate generality remains a significant challenge and has not yet been reported. Herein, we developed the nickel-catalyzed intramolecular radical cyclization of 2-bromo-2,2-difluoro-N-(2-cyanoaryl)acetamides to achieve various 3,3-difluoro-quinoline-2,4-diones in good yields. The scalability and practical applicability of this method were demonstrated through large-scale reactions. Full article

Antibiotic residues in water buffalo milk are a food-safety concern, yet depletion data are scarce. The purpose of this study was to characterize the depletion profiles of amoxicillin (AMOX) and its two major metabolites, amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2′,5′-dione (2,5-DKP), in Anatolian water buffalo milk after a single intramuscular administration and to estimate a milk withdrawal time relative to the EU MRL. We tested the hypothesis that AMOX concentrations would decrease below the EU MRL over successive milkings and that AMA and 2,5-DKP would exhibit depletion kinetics distinct from the parent compound. Five lactating Anatolian water buffaloes received a single intramuscular injection of amoxicillin (15 milligrams per kilogram). Milk was collected at each milking (twice daily) for seven days and analyzed by liquid chromatography–tandem mass spectrometry with quantification limits below the European Union maximum residue limit for amoxicillin in milk (4 micrograms per kilogram). Amoxicillin peaked at the second milking (mean 13.65 micrograms per kilogram), mean concentrations fell below the maximum residue limit from the sixth milking, and they became non-quantifiable from the tenth milking onward. Two major metabolites, amoxicillinic acid and amoxicillin diketopiperazine-2′,5′-dione, peaked earlier (2,5-DKP Tmax 12 h) or at higher concentrations (AMA Cmax 32.64 µg/kg vs. AMOX 13.65 µg/kg) and remained detectable up to the thirteenth milking, with longer apparent terminal half-lives (32.0 and 52.8 h) than amoxicillin (23.5 h); the mixed-effects model confirmed different depletion rates among analytes (milking × analyte interaction p = 4.63 × 10⁻⁵). A log-linear withdrawal model applying the EMA 95/95 tolerance limit indicated that the first time point at which the upper tolerance limit fell below the EU MRL was 84.7 h after dosing; rounded up to the next 12 h milking interval, this corresponds to a reported withdrawal period of 96 h (≈8 milkings). These results provide species-specific residue kinetics for amoxicillin in Anatolian buffalo milk and support considering metabolites in monitoring and withdrawal-time decisions. Full article

The present study was to evaluate the analgesic activity of two newly synthesized 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives, designated DSZ-13 and DSZ-19. To achieve the desired result, the in vitro XTT cell proliferation assay, serotonin 5-HT_1A receptor affinity and COX-1 and COX-2 enzyme inhibition potential of the compounds were conducted by real-time qPCR. Non-compartmental analysis was used to estimate the pharmacokinetic parameters of the compounds in serum and brain tissue. The analgesic activity was evaluated using various in vivo pain models, encompassing acute pain (hot plate test), tonic pain (formalin test), neurogenic pain (capsaicin test), carrageenan-induced acute inflammation, and neuropathic pain models. Both compounds showed moderate affinity for serotonin 5-HT_1A receptors, a lack of cytotoxic activity, desirable pharmacokinetic parameters and slightly reduced mRNA expression for COX-1 and COX-2. Only the DSZ-19 revealed central/supraspinal analgesic activity and did not affect movement. Both compounds attenuated tonic and neurogenic pain, in the formalin and capsaicin tests, respectively. In addition, the involvement of the 5-HT_1A receptors in the formalin test was confirmed. Both compounds also showed antiallodynic activity in the oxaliplatin- and streptozotocin-induced neuropathy models. Slightly weaker than indomethacin, DSZ-13 and DSZ-19 attenuated carrageenan-induced inflammation (edema) and hyperalgesia in rat models. Full article

A green and efficient method was developed for the synthesis of 1,8-dioxo-octahydroxanthene derivatives using linear alkylbenzene sulfonic acid (LABSA) as an eco-friendly Brønsted acid catalyst under aqueous reflux conditions. This system combines micellar catalysis and acid activation to afford tricyclic products in high yields and with excellent purity. The transformation proceeds via a Knoevenagel–Michael sequence between dimedone and aromatic aldehydes, followed by intramolecular cyclization. The method exhibits broad substrate tolerance, affording yields between 80 and 92. The simplicity, scalability, and environmental compatibility of this process establish LABSA as a promising alternative to conventional acids for the green synthesis of pharmacologically relevant xanthene derivatives. Full article

Hydantoins, exemplified by the imidazolidine-2,4-dione core, are privileged scaffolds in medicinal chemistry due to their compact structure, versatile hydrogen-bonding capacity, ability to fine-tune physicochemical properties for drug-like molecules, and potential to engage a diverse array of biological targets. This review highlights major advances in hydantoin-based drug discovery since 2019, emphasizing their evolving applications in oncology; neurology; infectious diseases; and cardiovascular, metabolic, and immune disorders. Recent studies demonstrate their success as kinase inhibitors, androgen receptor antagonists, and metalloprotease inhibitors, and emerging roles in modulating sterol isomerase, glycogen synthase kinase-3β, and ADAMTS family enzymes. Novel hybrid scaffolds—such as catechol–hydantoins, β-carboline–hydantoins, and spirocyclic thiohydantoins—have yielded potent and selective anticancer and antiviral leads. The discovery of BAY-9835 and GLPG1972 underscores the clinical potential of hydantoin-based metalloproteinase inhibitors in cardiovascular and osteoarthritic conditions. Furthermore, new antimicrobial, antimalarial, and antileishmanial derivatives illustrate the scaffold’s capacity to address multidrug resistance and neglected tropical diseases. Advances in computational design, stereochemical optimization, and hybridization strategies have expanded the structural and functional diversity of hydantoins, enhancing their target selectivity and pharmacokinetic profiles. Overall, hydantoins and their analogs remain at the forefront of small-molecule drug discovery, offering rich prospects for therapeutic innovation in diverse disease areas. Full article

Background: A debilitating complication of diabetes is diabetic peripheral neuropathy (DPN), for which effective therapy remains limited. In this research, we evaluated the effects of quercetin, pioglitazone, insulin, and a novel thiazolidine-2,4-dione derivative (TZDd) on the nerve functions in a streptozotocin (STZ)-induced rat model of DPN. Methods: In the experimental groups, STZ (60 mg/kg) was administered to Wistar rats to induce type 1 diabetic neuropathy, and the control and experimental DPN groups were treated with quercetin, pioglitazone, insulin, or TZDd for 5 weeks. The sensory and motor symptoms of DPN were evaluated via behavioral tests, nerve conduction velocity measurements, and electrophysiological assessment, and the synthesized TZDd was evaluated in silico for its pharmacokinetic, toxicological, and drug-likeness properties. Results: The diabetic rats developed DPN after 2 weeks of STZ administration, as evidenced by the significant reduction in the sensory and motor nerve conduction velocities (SNCVs and MNCVs) and increased mechanical hyperalgesia; on the other hand, quercetin, pioglitazone, insulin, and TZDd administration ameliorated the nerve functions of the DPN rats. In the in silico predictions, the novel TZDd exhibited no toxicity risks and demonstrated drug-like properties. Conclusions: Quercetin, pioglitazone, insulin, and TZDd showed neuroprotective effects that enhanced functional recovery in experimental DPN. These findings highlight that TZDd may represent a valuable compound with neuroprotective effects that could be used in DPN therapy and management. Full article

Stretchable semiconductors capable of maintaining electrical performance under large mechanical deformation are essential for reliable wearable electronic devices. However, polymer semiconductors often suffer from electrical degradation when subjected to tensile strain. In this study, electrical stability under strain was achieved by using a rubber-blended poly(2,5-bis(2-octyldodecyl)-3,6-di(thiophen-2-yl)diketopyrrolo[3,4-c]pyrrole-1,4-dione-alt-thieno[3,2-b]thiophene) (DPPT-TT) polymer semiconductor based on a conjugated polymer/elastomer phase separation-induced elasticity (CONPHINE) structure. Unlike most previous studies on fully stretchable thin-film transistors (TFTs), which primarily report overall performance changes under mechanical strain, this work systematically identifies the dominant origin of electrical performance degradation through a stepwise electrical analysis encompassing the gate insulating layer, the semiconductor layer, and complete devices. Bottom-gate top-contact (BGTC) and bottom-gate bottom-contact (BGBC) devices were fabricated on rigid Si/SiO₂ substrates to examine the intrinsic properties of the DPPT-TT/styrene-ethylene-butylene-styrene (SEBS) CONPHINE film. As a result, the device exhibits 90% mobility retention even at 100% tensile strain applied parallel to the charge transport direction. Quantitative resistance analysis using the Y-function method reveals that variations in channel resistance play a dominant role in strain-induced performance degradation, whereas changes in contact resistance contribute only marginally. These findings demonstrate that stabilizing channel resistance, rather than contact resistance, is important for achieving high mobility retention under large mechanical deformation, thereby providing concrete and quantitative design guidelines for reliable stretchable TFTs. Full article