In this study, the multicomponent synthesis of hydantoins was investigated using density functional theory (DFT) at the B3LYP/6-311G level to elucidate the reaction mechanism in diethyl ether. All reaction pathways were explored, intermediate structures were optimized, and relevant transition states were identified. A detailed computational analysis of the structures of the compounds was performed. Additionally, the relationship between energy and the structural properties of the molecules was assessed. In this study, ethanol was considered as a solvent. Each synthetic route involved the reaction of benzaldehyde, potassium cyanide, ammonium, and ammonium carbonate to yield the proposed product. The computational results indicated that the most favorable mechanism involved a seven-step pathway, with the highest activation energy observed at the fifth step, which was lower than that of the other steps.

Biofilm formation and the activity of efflux pumps are major contributors to antibiotic resistance in clinical strains of Pseudomonas aeruginosa and significantly enhance the pathogenicity of this bacterium. Functionalization of metal nanoparticles with plant-derived flavonoids, particularly when combined with conventional antibiotics, represents a promising strategy for overcoming antimicrobial resistance. In the present study, we investigated the synergistic inhibitory effects of quercetin-functionalized magnetic nanoparticles (Fe3O4@SiPr@Quercetin NPs) in combination with ciprofloxacin against ciprofloxacin-resistant clinical isolates of P. aeruginosa. Ciprofloxacin-resistant isolates were collected from hospitals and diagnostic laboratories in Tehran Province, Iran. The synthesized nanoparticles exhibited a spherical morphology with an average diameter of 165 nm. Synergistic antibacterial activity of the functionalized nanoparticles combined with ciprofloxacin was evaluated using the checkerboard assay. The most pronounced reduction in biofilm formation, was observed in strains treated with the nanoparticle–ciprofloxacin combination, with inhibition rates ranging from 18.9 ± 1.13

Fe3O4@SP-VNL-TGA MNCs (bis(thioglycolic acid)-vanillin(2,2’-(((4-hydroxy-3-methoxyphenyl)methylene)bis(sulfanediyl))diacetic acid)‐functionalized silica‐coated Fe3O4 magnetic nanocomposite) were synthesized and characterized by FE-SEM, TEM, VSM, XRD, TGA, EDX, and FT-IR. Fe3O4@SP-VNL-TGA offer an eco-friendly method for the preparation of novel 5-pyrazolyl-pyridine-3-carbonitriles through one-pot reaction of the corresponding pyrazolyl carbaldehydes, various acetophenones, malononitrile, and ammonium acetate. The compounds were obtained in high yields and short reaction times. The catalyst was effectively recovered and reused for six cycles with nearly the same activity. The structures of the synthesized 5-pyrazolyl-pyridine-3-carbonitriles were confirmed by 1H and 13C NMR spectroscopy, mass spectroscopy, FT-IR and elemental analyses.

INTRODUCTION:Benzoimidazo[1,2-a]pyrimidines are important compounds that have many useful effects in the body. They can help fight cancer, fungal infections, inflammation, and viruses. They can also help with various other health conditions. They can act as antineoplastic, antitubercular, parasitical activity, benzodiazepine receptor agonists, calcium channel blockers, potent P38 MAP kinase inhibitors, TIE-2 and/or VEGFR2 inhibitory activities, protein kinase inhibitors, and T cell activation. There are different methods to make the benzoimidazo[1,2- a]pyrimidines. Some of them dealth with the one-pot threecomponent condensation reactions of β- dicarbonyl compounds, aldehyde and 1H-benzo[d]imidazol-2-amine in the presence of catalyst. Although the synthesis of this group of compounds has been done before, and the products have been identified from the spectroscopic point of view, the kinetics and reaction mechanism have not been investigated. The strength of these calculations is that evaluation of the activation energy of various steps suggests possible mechanisms, probable mechanisms, and valuable synthetic intermediates. METHODS:In this report, seven possible mechanisms for synthesizing the benzoimidazo[1,2- a]pyrimidines have been investigated using density functional theory (DFT) at the B3LYP/6- 311G** level of theory. Each synthetic route involves condensation of the benzaldehyde, indanedione and 1H-benzo[d]imidazol-2-amine molecules to yield the proposed product. The calculations showed that the suggested method has six steps; its initiation step includes the Knoevenagel reaction between indanedione and aldehyde, and the rate determining state is dehydration in the fifth step. RESULTS:Six potential pathways for the reaction will occur. Then, we focused on the best pathway and studied it in detail. The ways that three chemicals-indanedione (R1), benzaldehyde (R2), and 1H-benzo[d]imidazol-2-amine (R3) react with each other were studied using ab-initio program by ChemBio3D, Gauss View, and Gaussian 09. The Density Functional Theory (DFT) using the B3LYP basis set was used to improve the arrangement of molecules involved in the three-part creation of a specific compound called 12-phenyl-5H-benzo[4,5]imidazo[1,2-a]indeno[1,2- d]pyrimidin-13(12H)-one (P). CONCLUSION:During the study of the six mechanisms, the proposed pathway 2 is the best mechanism for this reaction because its rate-determining step has the lowest activation energy value. This route consists of 6 steps, the fifth step of which is related to the conversion of IM4 to IM5 (relative ΔE: 109.80 Kj/mol), during which a dehydration reaction is performed, and this step occurs by passing through transition state TS5 (Total Energy (Hart./particles: -1194.747403).

Silibinin-loaded micelle/liposome nanocarriers (SMLNs) were successfully synthesized and characterized using FT-IR, SEM, TEM, XRD and TGA analyses. The nanocarriers exhibited an average particle size of 16.33 nm as determined by TEM imaging and less than 60 nm by FE-SEM analysis. They displayed an amorphous structure, and high thermal stability, maintaining integrity at temperatures exceeding 650 °C. The silibinin loading content and entrapment efficiency were 3.2

In this study, the synthesis of new chromenopyrimidinebenzene sulfonate derivatives was investigated. The first step of the reaction involved using 4-hydroxy or 2-hydroxybenzaldehyde, p-toluene or benzene sulfonyl chloride, and DABCO in acetonitrile to produce 2-formylphenylbenzene (p-tolyl)sulfonate derivatives. Subsequently, these derivatives were reacted with 2-hydroxybenzaldehyde, ethyl cyanoacetate, and ammonium acetate in a deep eutectic solvent (choline chloride:urea) to synthesize chromenopyrimidine derivatives. Finally, by reacting the chromenopyrimidine derivatives with p-toluene or benzenesulfonyl chloride in DABCO in DMF at room temperature, new chromenopyrimidinebenzene sulfonate derivatives were obtained. Chromeno[2,3-d]pyrimidine 4a and its benzenesulfonate esters 5a-5e were tested against Staphylococcus aureus and Escherichia coli. Compound 4a showed strong broad-spectrum activity. Compound 5d containing p-tolyl sulfonate exhibited the highest potency against E. coli due to improved membrane permeability, while 5e was less active. Compounds 4a and 5d were identified as lead candidates for further optimization.

Fe3O4@SP-VNL-TGA MNCs (bis(thioglycolic acid)-vanillin(2,2'-(((4-hydroxy-3-methoxyphenyl)methylene)bis(sulfanediyl))diacetic acid)-functionalized silica-coated Fe3O4 magnetic nanocomposite) were synthesized and characterized by FE-SEM, TEM, VSM, XRD, TGA, EDX, and FT-IR. Fe3O4@SP-VNL-TGA offer an eco-friendly method for the preparation of novel 5-pyrazolyl-pyridine-3-carbonitriles through one-pot reaction of the corresponding pyrazolyl carbaldehydes, various acetophenones, malononitrile, and ammonium acetate. The compounds were obtained in high yields and short reaction times. The catalyst was effectively recovered and reused for six cycles with nearly the same activity. The structures of the synthesized 5-pyrazolyl-pyridine-3-carbonitriles were confirmed by H-1 and C-13 NMR spectroscopy, mass spectroscopy, FT-IR and elemental analyses.

Bisabolol oxide A, a key bioactive constituent of Matricaria chamomilla, is recognized for its potent anti-inflammatory, antioxidant, and anticancer properties. This study focused on synthesizing bisabolol oxide A-loaded micellar/liposomal nanoparticles (NPs) and rigorously evaluating their anti-proliferative and anti-invasive effects using integrated in vitro and in silico methodologies. Physicochemical characterization of the bisabolol oxide A-loaded NPs was performed using SEM, TEM, TGA-DTG, Zeta potential, DLS analysis, and FT-IR spectroscopy. Furthermore, drug-like properties for bisabolol oxide A, bisabolol oxide B, and 5,8,11-heptadecatriynoic acid methyl ester were predicted using Swiss ADME software. Molecular dynamics simulations were subsequently conducted for these compounds against critical cellular migration proteins: β-catenin and the Epidermal Growth Factor Receptor (EGFR). The anticancer efficacy of the bisabolol oxide A-loaded nanoparticles was assessed through MTT assays, Annexin V/PI staining, wound healing assays, and qRT-PCR. Characterizations confirmed that the nanoparticles possessed optimal characteristics, exhibiting sizes between 35 to 67 nm, high mono-dispersity and thermal stability up to 380°C. In vitro results demonstrated that bisabolol oxide A-loaded micellar/liposomal nanoparticles significantly inhibited DU-145 cell proliferation, yielding IC₅₀ value of 55.44 µg/mL, 46.21 µg/mL, and 43.59 µg/mL after 24, 48, and 72 hours of treatment. Flow-cytometry analysis further confirmed 50.04

Chromium (III) coordinated to 2-[(2-amino-ethylimino) methyl]-6-methoxyphenol decorated Fe3O4@Silicapropyl Nps was synthesized and characterized by FT-IR, FE-SEM, TEM, XRD, VSM, TGA-DTG, DLS, and EDX. Then, the application of this new nano catalyst for the Synthesis of 2,3-dihydroquinazolin-4(1H)-ones via direct cyclocondensation reaction of various aldehydes and 2-aminobenzamide was investigated. The procedure proceeded in high yields and short reaction times. Easy preparation of the catalyst, easy work-up, and use of solvent-free conditions are the main advantages of the protocol. The nanocatalyst can be reused for six reaction cycles with no notable decrease in catalytic efficiency.

Silver nanoparticles show promise anticancer agents, yet their clinical translation is hindered by poor bioavailability and nonspecific toxicity. In this study, we developed an apigenin-functionalized silica-coated silver oxide nanocomposite (Ag2O@SP@Apigenin) and evaluated its anticancer activity against AGS human gastric adenocarcinoma cells. Silver nanoparticles were synthesized via chemical reduction, followed by silica-coated using 3-chloropropyltrimethoxysilane, and functionalization with apigenin under alkaline conditions. Successful synthesis and surface modification were confirmed by FTIR, FE-SEM, TEM, TGA, and complementary analyses. The nanocomposite exhibited a spherical morphology with an average size of 99.45 nm. Thermal analysis revealed high stability, with only 2.572

Increased biofilm formation and efflux pumps activity are two major contributors to the antimicrobial resistance in clinical isolates of Pseudomonas aeruginosa (P. aeruginosa). In the present study, curcumin-functionalized Fe3O4 nanoparticles were synthesized and evaluated for their anti-biofilm and efflux pump inhibitory effects against P. aeruginosa. The nanoparticles, designated Fe3O4@SBA-3@Curcumin, were prepared via co-precipitation method followed by surface functionalization. Comprehensive physicochemical characterization was performed using thermal analysis and multiple spectroscopic techniques. The antimicrobial efficacy of Fe3O4@SBA-3@Curcumin alone and in combination with ciprofloxacin was assessed using fractional inhibitory concentration (FIC) analysis, biofilm formation assays, and pyocyanin production measurements. FT-IR spectroscopy confirmed successful curcumin functionalization without structural degradation. FE-SEM and TEM images demonstrated nanoparticle size of 52.12 nm and 32.20 nm, respectively. Dynamic light scattering (DLS) analysis revealed a mean particle diameter of 101.8 nm and excellent colloidal stability, as indicated by a zeta potential of -86.8 mV. Combination therapy exhibited a synergistic effect and significantly reduced biofilm formation and pyocyanin production. Furthermore, combined treatment with Fe₃O₄@SBA-3@Curcumin and ciprofloxacin resulted in downregulation of efflux pump genes (mexA, mexB, and oprM) and biofilm-associated genes (algD and pelA). Molecular docking analyses predicted favorable binding interactions between curcumin and key biofilm-related proteins involved in exopolysaccharide synthesis (algD and pelD), as well as efflux pump components associated with antibiotic resistance (mexB, mexA, and oprM) in P. aeruginosa. Collectively, these findings support the potential role of curcumin functionalization in attenuating biofilm formation and efflux pump activity. Overall, Fe₃O₄@SBA-3 nanoparticle may serve as an effective nanocarrier for targeted drug delivery into bacterial cells.

A series of azo-linked pyrazolophthalazine-5,10-diones (APPDs) were synthesized via multicomponent reaction of phthalic anhydride, synthetized azo-aldehyde, malononitrile, and hydrazine hydrate using the gabapentin (GBP) functionalized silica coated Fe3O4 magnetic nano composites (MT@SP@GBP MNCs) as a catalyst. All derivatives were characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. MT@SP@GBP MNCs was characterized by FT-IR, FE-SEM, TEM, TGA, XRD, EDX and VSM.

A novel, environmentally friendly, and solvent-free approach utilizing mechanochemical method is presented for the synthesis of aryldiazenyl-2-diindolylmethylphenol derivatives. This method involves a three-component reaction between aryldiazenylaldehydes and two equivalents of various indoles, employing a recyclable magnetic nanocatalyst, specifically Fe3O4@SiPr@gabapentin magnetic nanocomposites (MNCs). The characterization of the structure and morphology of the Fe3O4@SiPr@gabapentin MNCs was conducted using several techniques, including Fourier transform-infrared spectroscopy (FT-IR), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), zeta potential measurements, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and a vibrating sample magnetometer (VSM). The structural confirmation of the synthesized aryldiazenyl-2-diindolylmethylphenol compounds was achieved through FT-IR, 1H NMR, 13C NMR spectrometry, and elemental analysis. Also, after synthesizing these heterocyclic compounds, their antioxidant activities were studied using the 1,1-diphenyl-2-picrylhydrazyl (DPPH).

Silibinin, a major bioactive compound extracted from Silybum marianum, possesses notable antioxidant, antitumor, hepatoprotective, and antibacterial activities. However, its poor solubility limits its clinical applications. This study aimed to enhance the delivery of silibinin by synthesizing magnetic nanocomposites (MNCs) and evaluating their efficacy against clinical isolates of Pseudomonas aeruginosa and HepG2 cancer cells. The physicochemical properties of the Fe3O4@SiPr@Silibinin nanocomposites were characterized by FT-IR, TGA-DTG, TEM, FE-SEM, XRD, and VSM analysis. Clinical isolates and a standard strain of P. aeruginosa were treated with Fe3O4@SiPr@Silibinin (at sub-MIC level) in combination with ciprofloxacin (sub-MIC), and the results were compared to treatment with ciprofloxacin alone. Additionally, the anticancer effects of Fe3O4@SiPr@Silibinin were evaluated in HepG2 cells. The nanocomposites, with particle sizes ranging from 40 to 80 nm, significantly enhanced the antimicrobial activity of ciprofloxacin when used in combination. Treatment with Fe3O4@SiPr@Silibinin plus ciprofloxacin led to a downregulation of biofilm and efflux pump-related gene expression compared to ciprofloxacin treatment alone. Furthermore, Fe3O4@SiPr@Silibinin exhibited anti-cancer activity against HepG2 cells, with an IC₅₀ value of 35.79 µg/mL In Silibinin-treated HepG2 cells, upregulation of the P53 gene and downregulation of the Bcl2 gene were observed. Our findingssuggest that Fe3O4@SiPr@Silibinin MNCs, with high stability and water solublity, can efficiently deliver silibinin into pathogenic and tumorigenic cells, thereby enhancing its therapeutic effects against P. aeruginosa and HepG2 cells. Given the antimicrobial and antitumor properties of silibinin, these magnetic nanocarriers represent a promising strategy for its targeted delivery.

Multidrug-resistant uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infections, largely due to efflux pump overexpression, porin alterations, and increasing biofilm formation. To address these challenges, we developed bisabololoxide A-loaded PEG400-oleate polymeric nanoparticles (BAPNs) and evaluated their potential to enhance the efficacy of ciprofloxacin against ciprofloxacin-resistant isolates. BAPNs were synthesized and characterized by FTIR, TEM, FE-SEM, EDX, TGA, and zeta potential analysis. The synergistic effects of BAPNs and ciprofloxacin were evaluated in drug-resistant isolates. The inhibition of Biofilm formationwas quantified by crystal violet staining and gene expression changes in some genes related to efflux pumps, porins and biofilm formation were analyzed in two representative isolates by qPCR. BAPNs exhibited a spherical morphology with sizes ranging from 17 to 28 nm (TEM) and 30–43 nm (FE-SEM). Checkerboard analysis showed that the MIC of ciprofloxacin decreased by 2- to 32-fold in ciprofloxacin-resistant isolates and the ATCC 8739 strain when combined with BAPNs. Biofilm inhibition was significantly enhanced with the combined therapy compared to ciprofloxacin alone. qPCR analysis further revealed significant downregulation of the AcrAB-TolC efflux pump genes and the virulence genes fimH and hlyA, along with upregulation of the porin genes (ompC and ompF). Furthermore, molecular docking analysis confirmed the strong binding affinities of bisabololoxide A with virulence-associated proteins of E. coli. Our findings suggested that BAPNs may significantly potentiate ciprofloxacin activity by inhibiting efflux pump expression and biofilm formation, and increase of cell membrane permeability to drugs (with enhancing porins), thereby restoring susceptibility in resistant UPEC isolates. These results highlight BAPNs as a promising adjunctive nanocarrier strategy to overcome ciprofloxacin resistance in uropathogenic E. coli. Further validation in larger isolate panels and in vivo studies is warranted.

Kit-6-NH2@Vanillin@ alpha-methyleneacetophenone @ acridine-Cu (I) nanoparticles were synthesized and were characterized completely. Then, the application of this new nano catalyst for the preparation of azo-derived dihydropyridines (acridines) via the treatment between dimedone, aldehydes, and 4-aminoazobenzene was investigated. The procedure proceeded in suitable yield and good reaction speed. Easy preparation of the catalyst, simple isolation and use of solvent-free condition are the main advantages of the protocol. The nanocatalyst can be reused for nine reaction cycles with no notable decrease in catalytic efficiency. Background: 1,4-Dihydropyridine (DHP) derivatives are used in medicines and other products. After Hantsch method for the synthesis of DHPs, various modifications were carried out on this method such as using different catalysts in refluxing solvent, under ultrasound irradiation, microwave condition, and solvent-free procedure. These methods suffer from many problems such as: use of complex reagents, high consumption of solvent, long time and in some cases low reaction efficiency. While some methods work well, it is important to find a better catalyst for making 1,4-DHPs. Method: 1 mmol of 4-aminoazobenzene, 1 mmol of aldehyde, 2 mmol of dimedone and 0.05 g of catalyst were mixed and was stirred at room temperature. The reaction progress was controlled by TLC (4:1 Ethylacetate:nhexane). After required reaction time monitored by TLC, 10 mL of hot EtOH was added to mixture. The catalyst was separated by filtration and reused for successive run. Key finding: This is the first report for the synthesis of azo-linked dihydropyridines using Kit-6-NH2@Vanillin@alpha methyleneacetophenone@ acridine-Cu(I). Shorter reaction time and higher yield rather than most of reported methods are two major benefits of this work. The reaction was carried out under solvent-free condition and there is no need to use organic and hazardous solvents in this procedure. The reaction was carried out at room temperature that need no heating and it is based on green chemistry rules because is energy-economical.