Search Results (281)

A new synthetic strategy for pyrazolo[1,5-d][1,2,4]triazin-7(6H)-ones 4 through intramolecular cyclization of alkyl 2-(4-nitro-1H-pyrazol-3-yl)methylene)hydrazine-1-carboxylates 3 is described, allowing us to selectively modify the N-substituent in 3-position. The reduction in nitro compounds 4 with tin(II) chloride leads to amines 5, and their acetylation leads to acetamides 6. Via alkylation of 4 with bromoacetic acid alkyl esters and 2-chloro-5-(chloromethyl)pyridine, and the subsequent reduction in alkylated nitro compounds 7, the corresponding amines 8 and amides 9 were accessible in very good yields. The molecular structure of ethyl 2-(2-morpholino-3-nitro-7-oxopyrazolo[1,5-d][1,2,4]triazin-6(7H)-yl)acetate (7b) was confirmed by single-crystal X-Ray diffraction analysis. Antibacterial and cytotoxic properties were evaluated for 61 synthesized compounds. Full article

Certain foods and specific drugs have been linked to epilepsy in the literature. Here, we query PubMed citations for the co-occurrence of epilepsy with foods and drugs, using a list of 217,776 molecules from the HMDB. Notably, the top associations with epilepsy include approved drugs and drug families, diagnostic markers, inducers, and vitamins. Drugs include fosphenytoin (40%), topiramate (37%), valproic acid (34%), hydantoin (20%), phenytoin (31%), carbamazepine (33%), carbamazepine-10,11-epoxide (40%), trimethadione (31%), gabapentin (14%), pregabalin (11%), flunarizine (7%), fenfluramine (4%), bumetanide (4%), KBr (18%), cannabidiol (14%), clonazepam (22%), nitrazepam (10%), diazepam (7%), lorazepam (6%), midazolam (3%), amobarbital (21%), phenobarbital (16%), flumazenil (7%) allopregnanolone (7%), pregnanolone (6%), epipregnanolone (6%), 3-hydroxypregnan-20-one (6%), and vitamin B6 (6%). Drug families and scaffolds include imidazolidine (18%), succinimide (10%), acetamide (7%), 2-pyrrolidinone (7%), pyrrolidine (6%), tetrahydropyridine (6%), and isoxazole (4%). Investigational compounds include cyano-7-nitroquinoxaline-2,3-dione (5%). Diagnostic markers include exametazime (10%) and quinolinic acid (3%). Inducers include flurothyl (37%), pentetrazol (32%), pilocarpine (25%), (+)-Bicuculline (8%), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP, 6%). Our analysis highlights frequently cited associations between epilepsy and specific drugs and highlights the importance of supplementing nutrients with vitamin B6 and the ketogenic diet, which increases the gamma-aminobutyric acid (GABA)/glutamate ratio. As such, our study offers dietary approaches in the treatment of this neurodegenerative disease. Full article

Cobalt, a rare element in the Earth’s crust, is widely used in industries due to its hardness and antioxidant properties. It also plays a vital role in physiological functions, being a key component of vitamin B₁₂. However, excessive cobalt intake can cause health issues. Detecting cobalt ions, especially Co²⁺, in food is crucial due to potential contamination from various sources. Fluorescent probes offer high sensitivity, selectivity, a rapid response, and ease of use, making them ideal for the accurate and efficient recognition of Co²⁺ in complex samples. In this context, a highly selective fluorescent probe, 2,2′-((3-(1H-benzo[d]imidazol-2-yl)-1,2-phenylene) bis(oxy)) bis(N-(quinolin-8-yl) acetamide) (DQBM-B), was synthesized using chloroacetyl chloride, 8-aminoquinoline, 2,3-dihydroxybenzaldehyde, and benzidine as raw materials for the recognition of Co²⁺. Probe DQBM-B can exhibit fluorescence alone in DMF. However, as the concentration of Co²⁺ increased, Photoinduced Electron Transfer (PET) occurred, which quenched the original fluorescence of the probe. Probe DQBM-B shows better selectivity for Co²⁺ than other ions with high sensitivity (detection limit: 3.56 μmol L⁻¹), and the reaction reaches equilibrium within 30 min. Full article

In this study, we isolated and identified bacteria from the feces of a diarrheal cynomolgus monkey. The results showed that the isolated strain was P. aeruginosa, named PA/CM-101101. Morphological observations indicated that when cultured on Luria–Bertani (LB) nutrient agar at 37 °C for 24 h, the strain formed smooth, slightly elevated colonies with neat and wavy edges. On acetamide agar at the same temperature and duration, the colonies appeared flat with irregular edges and a faint pink periphery, while the medium changed to rose-red; in LB broth at 37 °C for 24 h, the medium became turbid and yellowish-green. Gram staining revealed that it was negative and rod-shaped, without sporulation characteristics. The 16S rRNA gene sequence analysis showed that the sequence identity of the strain shared more than 98.4% similarity with 11 strains of P. aeruginosa from various sources in GenBank. The animal toxicity test showed that it had a strong pathogenic effect on mice. The results of drug sensitivity tests showed that strain PA/CM-101101 was sensitive to amikacin, azithromycin, cefoperazone, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, levofloxacin, meropenem, norfloxacin, ofloxacin, and polymyxin B; however, it displayed resistance to ampicillin, cefadroxil, cefazolin, erythromycin, and vancomycin. The research findings provide valuable insights for diagnosis and treatment strategies for cynomolgus monkeys. It also provides a reference for molecular epidemiological studies. To our knowledge, this is the first time P. aeruginosa isolated from the diarrhea feces of cynomolgus monkey has been reported. Full article

Marine tunicates are a very attractive and abundant source of secondary metabolites with chemical diversity and biological activity. Fractionation and purification of the organic extract of the Red Sea tunicate Didemnum species resulted in the isolation and identification of three new compounds, didemnosides A and B (1 and 2) and 1,1′,3,3′-bisuracil (3), together with thymidine (4), 2′-deoxyuridine (5), homarine (6), and acetamide (7). Planar structures of the compounds were explained through analyses of their 1D (¹H and ¹³C) and 2D (¹H–¹H COSY, HSQC, and HMBC) NMR spectra and high-resolution mass spectral determinations. Compound 1 exhibited the highest growth inhibition toward the MCF-7 cancer cell line with IC₅₀ values of 0.597 μM, while other compounds were inactive (≥50 μM) against this cell line. On the other hand, compounds 1, 2, and 4–7 moderately inhibited SW-1222 and PC-3 cells with IC₅₀ values ranging between 5.25 and 9.36 μM. Molecular docking analyses of the top three active compounds on each tested cell line exposed stable interactions into the active pockets of estrogen receptor alpha (ESR1), human topoisomerase II alpha (TOP2A), and cyclin-dependent kinase 5 (CDK5) which are contemplated as essential targets in cancer treatments. Thus, compound 1 represents a scaffold for the development of more effective anticancer drugs. Full article

For various applications, particularly in battery technology, there is a significant demand for uniform, high-quality lithium or lithium-coated materials. The use of electrodeposition techniques to obtain such materials has not proven practical or economical due to the low solubility of most lithium salts in suitable solvents. In this study, we propose efficient lithium electrodeposition processes and baths that can be operated at low temperatures and relatively low costs. We utilized organic solvents such as dimethyl acetamide (DMA), dimethylforamide (DMF), and dimethyl sulfoxide (DMSO), as well as a mixture of DMSO and ionic liquid [1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide BMIMTFSI]. Lithium salts such as LiCl, Li₂CO₃, and LiNO₃ were tested. Lithium metal was deposited on copper substrates at different temperatures and selected current densities within an argon-filled glovebox using a DC power source or a PARSTAT-4000A potentiostat. Cyclic voltammetry (CV) was employed to determine and compare the deposition processes. The obtained deposits were analyzed through visual inspection (photography) and scanning electron microscopy (SEM). Chemical analysis (ICP-OES) and XRD confirmed the presence of lithium and occasionally lithium hydroxide in the deposits. The best results were achieved with the deposition of lithium from DMSO-LiNO₃ and DMSO-BMIMTFSI-LiNO₃ systems. Full article

Leishmaniasis is a neglected tropical disease caused by Leishmania sp. The therapeutic arsenal is reduced and limited. In this context, acridine derivatives present themselves as promising leishmanicidal compounds. This paper involved synthesizing and evaluating the antileishmanial and immunomodulatory potential of spiro-acridine derivatives. Six spiro-acridine derivatives were obtained through nucleophilic substitution reactions between the acetohydrazide/acetamide intermediates and 9-carbaldehydeacridine, followed by spontaneous cyclization. IR, NMR, and HRMS confirmed the structures. These were analyzed in vitro against L. infantum and L. amazonensis to determine anti-promastigote, anti-amastigote, and cytotoxicity effects. Immunomodulatory activity was evaluated using CBA, DCF-DA, and DAF-FM diacetate. In silico evaluation included molecular docking and dynamics. The spiro-acridines showed a wide range of anti-promastigote activities (IC₅₀ = 0.73–234.95 µM) and non-toxicity to red blood cells. AMTAC-02 and ACMD-03 demonstrated satisfactory anti-amastigote effect (IC₅₀ = 10.47–13.50 µM), low toxicity to macrophages (CC₅₀ = 27.22–569.50 µM), and cytokine and reactive species modulation. Molecular docking proposed cysteine protease B of L. amazonensis as a target, and molecular dynamics analysis highlighted the complex’s stability using RMSD, R_g, SASA, DCCM, PCA, and MM-PBSA (ΔG = −65.225 kJ/mol). Furthermore, QM-MM calculation provided the best energy for ACMD-03 (−199.30 au). Hence, AMTAC-02 and ACMD-03 demonstrated antileishmanial potential, making them promising entities for the development of leishmanicidal drug candidates. Full article

An efficient Ni-catalyzed, Mn-mediated denitrogenative cross-electrophile coupling of N-alkyl-1,2,3-benzotriazinones with alkyl tosylates and mesylates for access to o-alkyl secondary benzamides is reported. The method uses inexpensive non-anhydrous dimethyl acetamide (DMA) in combination with tetrabutyl ammonium iodide (TBAI) as a co-catalyst to convert sulfonates into iodides in situ. Scope and limitations of the protocol have been demonstrated by >30 examples with yields up to 91%, showing a large electronic effect from the N-substituent in benzotriazinones. An unexpected steric acceleration has been observed from the core of benzotriazinones, not only promising a highly efficient access to 2-alkyl-2,3-disubstituted benzamides but also shedding light on the rate-limiting steps in the catalytic cycle. Full article

The morphology of Poly (vinylidene fluoride) (PVDF) membranes prepared via the nonsolvent-induced phase separation (NIPS) method was modulated by altering the dope solution with citric acid (CA) and titanium dioxide nanoparticles (nano-TiO₂) to optimize the β-phase content. Three series of dope solutions were prepared in dimethyl acetamide (DMAc): (i) TONx series contained 0.0–10% citric acid, (ii) Mx series contained 0.0–0.4% nano-TiO₂, and (iii) TAx series contained 5% CA and 0.0–0.40% nano-TiO₂. A field emission scanning electron microscopy (FESEM) study revealed that CA enhances pore opening, and nano-TiO₂ transforms the sponge-like uneven porous structures into a compact, relatively regular honeycomb structure in the PVDF membranes. The combined effect of CA and nano-TiO₂ in the dope solution made the channels and chambers of the membrane well organized, and the walls of the channels transformed from solid fibrils to cross-woven nanofiber-like entities. Porosity initially peaked at 84% in the TAx series, gradually decreasing to 72% with increasing nano-TiO₂ concentrations. X-ray diffraction (XRD), Fourier-Transformed Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC) revealed the presence of a combined relative amount of the β- and γ-polymorphs of 84% in a neat PVDF membrane, 88% in an Mx, and 96% in a TAx series membrane, with the β-PVDF constituting nearly the entire portion of the combined polymorphs. The presence of 96% electroactive polymorph content in the PVDF membrane is noteworthy, highlighting its potential biomedical and industrial applications. Full article

According to European reports, the population of Anguilla anguilla has declined to unsafe biological limits in most areas and current fisheries are unsustainable. Indeed, the European eel has been listed as a critically endangered species since the 1970s and has been on the IUCN Red List of Threatened Species since 2010. Glass eel fisheries in Europe are very limited, but illegal catches and international parallel trade are major threats to eel stocks due to their high commercial value. The main hypothesis of this study is that glass eels from each estuary have unique chemical profiles according to the ecological quality of the habitat. These unique chemical fingerprints were assessed using Chemical Integrating Approaches (CIA) based on multi-element (macro, trace and ultra-trace metals), global metabolome and stable isotope analyses. Thus, CIA are intended to be an effective chemical “weapon” to (i) fingerprint wild glass eels; (ii) fingerprint captive glass eels; (iii) authenticate and trace glass eels; and (iv) combat the illegal trade in juvenile European eels. The results of this study showed that Zn and Ni can fingerprint the chemical profiles of wild and captive glass eels and their geographical origin. In the same vein, metabolomes such as Butyric acid 4-vinylphenyl ester, N-(3-carboxypropanoyl)-Met, 2-(4-Methylphenyl)acetamide, N-formyl-glutamic acid, 3-Hydroxy-2-(3-methylbutanoylamino)propanoic acid, 4-Dodecylbenzenesulfonic Acid, Arginine and Pyrazole and the stable isotope 15N show potential as a chemical tools for glass eel traceability. Full article

Butachlor is a widely utilized acetamide herbicide noted for its systemic selectivity against pre-emergence grass weeds. Butachlor has negative effects on organisms and the environment, so it is necessary to screen degradation strains. In this investigation, Bacillus cereus strain DC-1 was isolated from soil persistently exposed to butachlor. Through rigorous single-factor and response surface analyses, strain DC-1 exhibited a notable 87.06% degradation efficiency under optimized conditions where the temperature was 32.89 °C, pH was 7.29, and inoculum concentration was 5.18%. It was further hypothesized by LC-MS that the degradation pathway of butachlor by strain DC-1 might be as follows: butachlor undergoes initial deoxygenation catalyzed by dioxygenases to form 2-chloro-N-(2,6-diethylphenyl)-N-methylacetamide, followed by N-demethylation yielding 2-chloro-N-(2,6-diethylphenyl) acetamide, and culminating in conversion to 2,6-diethylphenol. In addition, bioremediation experiments of butachlor-contaminated soil were conducted. The results show that strain DC-1 could degradable 99.23% of butachlor (100 mg·kg⁻¹) from the soil within 12 d, and soil sucrase, cellulase, and urease activities are promoted by the bacteria. And through high-throughput sequencing, it was concluded that the strain DC-1 was able to influence the relative abundance of certain bacteria in the soil, and make the microbial community in the soil develop in a more stable and beneficial direction. DC-1 thus represents a valuable resource in the realm of butachlor degradation due to its robust efficacy, favorable characteristics, and ecological restorative capabilities, underscoring its promising role in the bioremediation of butachlor-contaminated soils. Full article

A novel series of substituted benzofuran-tethered triazolylcarbazoles was synthesized in good to high yields (65–89%) via S-alkylation of benzofuran-based triazoles with 2-bromo-N-(9-ethyl-9H-carbazol-3-yl)acetamide. The inhibitory potency of the synthesized compounds against SARS-CoV-2 was evaluated by enacting molecular docking against its three pivotal proteins, namely, M^pro (main protease; PDB ID: 6LU7), the spike glycoprotein (PDB ID: 6WPT), and RdRp (RNA-dependent RNA polymerase; PDB ID: 6M71). The docking results indicated strong binding affinities between SARS-CoV-2 proteins and the synthesized compounds, which were thereby expected to obstruct the function of SARS proteins. Among the synthesized derivatives, the compounds 9e, 9h, 9i, and 9j exposited the best binding scores of −8.77, −8.76, −8.87, and −8.85 Kcal/mol against M^pro, respectively, −6.69, −6.54, −6.44, and −6.56 Kcal/mol against the spike glycoprotein, respectively, and −7.61, −8.10, −8.01, and −7.54 Kcal/mol against RdRp, respectively. Furthermore, the binding scores of 9b (−8.83 Kcal/mol) and 9c (−8.92 Kcal/mol) against 6LU7 are worth mentioning. Regarding the spike glycoprotein, 9b, 9d, and 9f expressed high binding energies of −6.43, −6.38, and −6.41 Kcal/mol, accordingly. Correspondingly, the binding affinity of 9g (−7.62 Kcal/mol) against RdRp is also noteworthy. Furthermore, the potent compounds were also subjected to ADMET analysis to evaluate their pharmacokinetic properties, suggesting that the compounds 9e, 9h, 9i, and 9j exhibited comparable values. These potent compounds may be selected as inhibitory agents and provide a pertinent context for further investigations. Full article

In the current study, pyromellitimide benzoyl thiourea cross-linked chitosan (PIBTU-CS) hydrogel, was evaluated as a green biocatalyst for the efficient synthesis of novel thiazole derivatives. The PIBTU-CS hydrogel showcased key advantages, such as an expanded surface area and superior thermal stability, establishing it as a potent eco-friendly catalyst. By employing PIBTU-CS alongside ultrasonic irradiation, we successfully synthesized a series of novel thiazoles through the reaction of 2-(4-((2-carbamothioylhydrazineylidene)methyl)phenoxy)-N-(4-chlorophenyl)acetamide with a variety of hydrazonoyl halides (6a–f) and α-haloketones (8a–c or 10a,b). A comparative analysis with TEA revealed that PIBTU-CS hydrogel consistently delivered significantly higher yields. This synthetic strategy provided several benefits, including mild reaction conditions, reduced reaction times, and consistently high yields. The robustness of PIBTU-CS was further underscored by its ability to be reused multiple times without a substantial reduction in catalytic efficiency. The structures of the synthesized thiazole derivatives were meticulously characterized using a range of analytical techniques, including IR, ¹H-NMR, ¹³C-NMR, and mass spectrometry (MS), confirming their successful formation. These results underscore the potential of PIBTU-CS hydrogel as a sustainable and recyclable catalyst for the synthesis of heterocyclic compounds. Additionally, all synthesized products were tested for their anticancer activity against HepG2-1 cells, with several new compounds exhibiting good anticancer effects. Full article

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare, serious, and pharmacoresistant epileptic disorder often linked to gain-of-function mutations in the KCNT1 gene. KCNT1 encodes the sodium-activated potassium channel known as SLACK, making small molecule inhibitors of SLACK channels a compelling approach to the treatment of EIMFS and other epilepsies associated with KCNT1 mutations. In this manuscript, we describe a hit optimization effort executed within a series of 2-aryloxy-N-(pyrimidin-5-yl)acetamides that were identified via a high-throughput screen. We systematically prepared analogs in four distinct regions of the scaffold and evaluated their functional activity in a whole-cell, automated patch clamp (APC) assay to establish structure-activity relationships for wild-type (WT) SLACK inhibition. Two selected analogs were also profiled for selectivity versus other members of the Slo family of potassium channels, of which SLACK is a member, and versus a panel of structurally diverse ion channels. The same two analogs were evaluated for activity versus the WT mouse channel as well as two clinically relevant mutant human channels. Full article

Inhibitors of NQO2 (NRH: quinone oxidoreductase) have potential application in several areas of medicine and pharmacology, including cancer, neurodegeneration (PD and AD), stroke, and diabetes. Here, resveratrol, a known inhibitor of NQO2, was used as the lead by replacing the double bond in resveratrol with a benzothiazole scaffold. Fifty-five benzothiazoles were designed as NQO2 inhibitors and synthesized, comprising five benzothiazole series with 3,5-dimethoxy, 2,4-dimethoxy, 2,5-dimethoxy, 3,4-dimethoxy, and 3,4,5-trimethoxy substituents, the key synthetic step being a Jacobson cyclisation with the appropriate thiobenzamide. All compounds were evaluated in an NQO2 enzyme inhibition assay, with four compounds having IC₅₀ values of <100 nM. The most active (IC₅₀ 25 nM) was 6-hydroxy-2-(3’,5’-dihydroxyphenyl)benzo[d]thiazole (15), a good mimetic of resveratrol. Three of the 3’,4’,5’-trimethoxybenzothiazole analogues, with 6-methoxy (40, IC₅₀ 51 nM), 6-amino (48, IC₅₀ 79 nM), and 6-acetamide (49, IC₅₀ 31 nM) substituents, were also potent inhibitors of NQO2. Computational modelling indicated the most active compounds exhibited good shape complementarity and polar interactions with the NQO2 active site. Through the inhibition of NQO2, benzothiazole-based compounds may have the potential to enhance the efficiency of cancer therapies or minimise oxidative damage in neuroinflammation. Full article