Search Results (58)

It is widely recognized that fine surface structures found in nature contribute to surface functionality, and studies on the design of functional materials based on biomimetics have been actively conducted. In this study, polymer thin films with hierarchically ordered surface structure were prepared by combining both nanoimprinting using anodically oxidized porous alumina (AAO) as a template and surface-initiated atom transfer radical polymerization (SI-ATRP). To prepare such polymer films, we designed a new copolymer (poly{[2-(4-methyl-2-oxo-2H-chromen-7-yloxy)ethyl methacrylate]-co-[2-(2-bromo-2-methylpropionyloxy)ethyl methacrylate]}; poly(MCMA-co-HEMABr)) with coumarin moieties and α-haloester moieties in the pendants. The MCMA repeating units function to fix the pillar structure by photodimerization, and the HEMABr ones act as the polymerization initiation sites for SI-ATRP on the pillar surfaces. Surface structures consisting of vertically oriented multiple pillars were fabricated on the spin-coated poly(MCMA-co-HEMABr) thin films by nanoimprinting using an AAO template. Then, the coumarin moieties inside each pillar were crosslinked by UV light irradiation to fix the pillar structure. SEM observation confirmed that the internally crosslinked pillar structures were maintained even when immersed in organic solvents such as 1,2-dichloroethane and anisole, which are employed as solvents under SI-ATRP conditions. Finally, poly(2,2,2-trifluoroethyl methacrylate) and poly(N-isopropylacrylamide) chains were grafted onto the thin film by SI-ATRP, respectively, to prepare the hierarchically ordered surface structure. Furthermore, in this study, the surface properties as well as the thermoresponsive hydrophilic/hydrophobic switching of the obtained polymer films were investigated. The surface morphology and chemistry of the films with and without pillar structures were compared, especially the interfacial properties expressed as wettability. Grafting poly(TFEMA) increased the static contact angle for both flat and pillar films, and the con-tact angle of the pillar film surface increased from 104° for the flat film sample to 112°, suggesting the contribution of the pillar structure. Meanwhile, the pillar film surface grafted with poly(NIPAM) brought about a significant change in wettability when changing the temperature between 22 °C and 38 °C. Full article

Non-Small Cell Lung Cancer (NSCLC) is the most typical kind of lung cancer. Chemotherapy, radiation therapy, and other traditional cancer therapies are ineffective. Advancements in understanding cancer’s molecular causes have led to targeted therapies, such as those addressing NTRK gene fusions in NSCLC. Several machine-learning techniques were used in our work, including k-Nearest Neighbors (kNN), Support Vector Machine (SVM), Random Forest (RF), and Naive Bayes (NB). As a result, the RF model outperformed the other studied machine-learning methods, achieving an astonishing 93.12% accuracy for both training as well as testing datasets, and it was employed to screen 9000 chemicals, resulting in the discovery of 65 putative NTRK potential inhibitors. The active sites of NTRK proteins were then docked with these 65 active chemicals. Our findings show that Gancaonin X, 5-hydroxy-2-(4-methoxyphenyl)-8,8-dimethyl-2,3-dihydropyrano[2,3-h]chromen-4-one, (2S)-7-[[(2R)-3,3-dimethyloxiran-2-yl]methoxy]-5-hydroxy-2-phenyl-2,3-dihydrochromen-4-one, (2S)-5-hydroxy-2-(4-methoxyphenyl)-8,8-dimethyl-2,3-dihydropyrano[2,3-h]chromen-4-one, and methyl 2-(methylamino)-5-[(3S)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-yl]benzoate establish strong interactions inside the binding region of NTRK, as a result of which stable complexes are formed. This study employs 100 ns molecular dynamics simulations to investigate the dynamic behavior of phytochemical-NTRK complexes, revealing stable interactions through RMSD, RMSF, Rg, and SASA analyses. The detailed examination of protein–ligand interactions provides crucial atomic-level insights, enhancing our understanding of potential neurotrophic receptor kinase-targeted therapeutic strategies. This highlights their significant ability as NTRK antagonists, giving novel treatment options for NSCLC therapy. To summarize, the application of machine learning in combination with virtual screening in this study not only can discover new NSCLC therapeutics but also highlight new computer approaches in the field of drug discovery. Full article

A series of 2- and 3-methoxyphenylpiperazine derivatives in combination with a 2-hydroxypropoxy linker and coumarins containing various substituents was synthesized and evaluated for antidepressant-like activity. Microwave-assisted synthesis was used, and the structures of all compounds were confirmed by ¹H, ¹³C NMR, and HRMS spectrometry. The affinity toward the 5-HT_1A and 5-HT_2A receptors was determined using radioligand binding assays and analyzed by molecular docking studies. Among the compounds evaluated, four demonstrated high affinity for the 5-HT_1A receptor with the following Ki values: 5-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propoxy)-4,7-dimethyl-2H-chromen-2-one (5) (90 nM), 6-acetyl-5-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propoxy)-4,7-dimethyl-2H-chromen-2-one (7) (90 nM), 7-(2-hydroxy-3-(4-(3-methoxyphenyl)piperazin-1-yl) propoxy)-4-methyl-2H-chromen-2-one (10) (87 nM), and 8-acetyl-7-(2-hydroxy-3-(4-(2-methoxy phenyl)piperazin-1-yl)propoxy)-4-methyl-2H-chromen-2-one (11) (96 nM), and four demonstrated high affinity for the 5-HT_2A receptor with the following Ki values: 6-acetyl-7-(2-hydroxy-3-(4-(3-methoxyphenyl)piperazin-1-yl)propoxy)-4-methyl-2H-chromen-2-one (2) (83 nM), 8-acetyl-7-(2-hydroxy-3-(4-(3-methoxyphenyl)piperazin-1-yl)propoxy)-4-methyl-2H-chromen-2-one (12) (67 nM), 7-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl) propoxy)-2H-chromen-2-one (13) (18 nM), and 7-(2-hydroxy-3-(4-(3-methoxyphenyl)piperazin-1-yl)propoxy)-2H-chromen-2-one (14) (68 nM). In functional assays, 8-acetyl-7-(2-hydroxy-3-(4-(2-methoxyphenyl) piperazin-1-yl)propoxy)-4-methyl-2H-chromen-2-one (compound 11) exhibited a significant 5-HT_1A antagonistic profile. Computational studies revealed the structural details responsible for the high affinity of selected derivatives, which were compared to known 5HT_1A partial agonists. Full article

In this study, the aerial parts of Scadoxus multiflorus were extracted using methanol through a maceration process. The resulting methanol crude extract was subsequently partitioned with solvents including n-hexane, chloroform, ethyl acetate, and n-butanol. Extensive column chromatography separation of the chloroform fraction, followed by isocratic elution of two pooled fractions, led to the isolation of two coumarin derivatives: 2-methyl-2H-chromen-7-ol and 7-methoxy-2H-chromen-2-one. These compounds underwent various physicochemical analyses, such as chemical tests, melting point determination, and solubility assessments. Structural elucidation of the isolated compounds was conducted using UV spectroscopy, FT-IR, and 1D/2D NMR techniques. The final molecular structures were confirmed and named using ChemDraw. Full article

Spring viremia of carp virus (SVCV) is a significant pathogen that has notably hindered the advancement of cyprinid aquaculture in recent years. Infections caused by SVCV are often associated with substantial economic losses due to the absence of effective treatment options. Previous reports indicated that N-(4-methyl-2-oxo-2H-chromen-7-yl) benzenesulfonamide (N6) exhibits inhibitory effects on SVCV proliferation. This study aims to comprehensively evaluate the anti-SVCV effects of N6 using healthy young carp as the experimental model. The research investigates the antiviral activity of this compound in vivo, the immune response of interferon (IFN)-related genes, its impact on the horizontal transmission of SVCV, and histopathological changes. The results indicate that N6 significantly inhibits SVCV infectivity and apoptosis in EPC cells in vitro. Furthermore, while N6 reduced horizontal transmission of SVCV in a static cohabitation challenge model, the N6-treated SVCV-infected group showed a nearly 3-fold decrease in viral load compared to the control group, it did not completely prevent transmission at established antiviral dosages. Histopathological analysis of the affected fish revealed that N6 effectively mitigated tissue damage induced by SVCV. Additionally, the up-regulation of six IFN-related genes suggests that N6 may indirectly activate IFNs to facilitate the clearance of SVCV in the kidney and spleen, as demonstrated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). These findings provide a foundation for further investigations into the mechanisms by which N6 acts against SVCV and may aid in the development of novel anti-SVCV therapeutics. Full article

Cyclodextrins (CDs) are natural cyclic oligosaccharides with the ability to form inclusion complexes with various organic substances. In this paper, we investigate the potential of CD complex formation to enhance the antibacterial activity and antioxidant properties of poorly soluble bioactive agents, such as chalcones, chromenes, stilbenoids and xanthylium derivatives, serving as potential adjuvants, in comparison with standard antiseptics. The interaction of these bioactive agents with the hydrophobic pocket of methyl-β-cyclodextrin (MCD) was confirmed using spectroscopic methods such as UV-vis, FTIR, ¹H and ¹³C NMR, mass-spectrometry. CD-based delivery system allows for combining multiple active agents, improving solubility, antibacterial efficacy by enhancing penetration into target bacterial cells (E. coli selectivity demonstrated via confocal microscopy). Novel compounds of chalcones and stilbenoids derivatives additionally enhance efficacy by inhibiting bacterial efflux pumps, increasing membrane permeability, and inhibiting bacterial enzymes, and showed a synergy when used in combination with metronidazole. The intricate relationship between the structural characteristics and functional properties of chalcones and stilbenoids in terms of their antibacterial and antioxidative capabilities is revealed. The substituents within aromatic rings significantly influence this activity, where position of electron-donating methoxy groups playing a crucial role. Among chalcones, stilbenoids, ana xanthyliums, the compounds caring a benzodioxol ring, analogous to natural bioactive compounds like apiol, dillapiol, and myristicin, emerge as prominent antibacterial activity. To explore the possibility to create theranostic formulations, we used fluorescent markers to visualize target cells, antiseptics to provide antibacterial activity, and bioactive agents as chalcones acting as adjuvants. Additionally, new antioxidant compounds were found such as Xanthylium derivative (R351) and chromene derivative: 1-methyl-3-(2-amino-3-cyano-7-methoxychromene-4-yl)-pyridinium methanesulfate: the pronounced antioxidant properties of these substances are observed comparable to quercetin in the efficiency. Rhodamine 6G, gentian violet, and Congo Red exhibit good antioxidant properties, although their activity is an order of magnitude lower than that of quercetin. However, they have remarkable potential due to their multifaceted nature, including the ability to visualize target cells. The most effective theranostic formulation is the combination of the antibiotic (metronidazole) + dye/fluorophore (methylene blue/rhodamine 6G) for visualization of target cells + adjuvant (chalcones or xanthylium derivatives) for antiinflammation effect. This synergistic combination, results in a promising theranostic formulation for treating bacterial infections, with enhanced efficiency, selectivity and minimizing side effects. Full article

We report a straightforward and efficient synthesis of 4-methyl-2-oxo-2H-chromen-7-yl benzenesulfonate (3a) and 8-iodo-4-methyl-2-oxo-2H-chromen-7-yl benzenesulfonate (3b) in good yields through an O-sulfonylation reaction of 7-hydroxy-2H-chromen-2-ones 1a and 1b with benzenesulfonyl chloride 2 mediated by triethylamine in dichloromethane at ambient temperature. The aryl sulfonyl esters were characterized using spectroscopic, spectrometric, and thermal analyses. Full article

In this study, we report the synthesis of (±)-2-chloro-N-(4-methyl-2-oxo-2H-chromen-7-yl)-2-phenylacetamide through the reaction of 7-amino-4-methyl-2H-chromen-2-one with (±)-2-chloro-2-phenylacetyl chloride. The in vitro anti-inflammatory activity of the new compound was evaluated, and the results indicated that it exhibited superior activity compared to the standard, ibuprofen. The bio-functional hybrid compound underwent thorough detailed characterization utilizing ¹H and ¹³C NMR, UV, and mass spectral analysis. Full article

The goal of this study was directed to synthesize a novel class of annulated compounds containing difuro[3,2-c:3′,2′-g]chromene. Friedländer condensation of o-aminoacetyl derivative 3 was performed with some active methylene ketones, namely, 1,3-cyclohexanediones, pyrazolones, 1,3-thiazolidinones and barbituric acids, furnished furochromenofuroquinolines (4,5), furochromenofuropyrazolopyridines (6–8), furochromenofurothiazolopyridines (9,10) and furochromenofuropyridopyrimidines (11, 12), respectively. Also, condensation of substrate 3 with 5-amine-3-methyl-1H-pyrazole and 6-amino-1,3-dimethyluracil, as cyclic enamines, resulted in polyfused systems 13 and 14, respectively. In vitro antimicrobial efficiency of the prepared heterocycles against microbial strains exhibited variable inhibition action, where compound 3 was the most effective against all kinds of microorganisms. A significant cytotoxic activity was seen upon the annulation of the starting compound with thiazolopyridine (9 and 10) as well as pyridopyrimidine moieties (11, 12 and 14). The spectroscopic and analytical results were used to infer the structures of the novel synthesized compounds. Full article

The tautomerism in the title compound as a potential long-range proton transfer (PT) switch has been studied by using the DFT and TD-DFT approaches. The data show that in aprotic solvents, the enol tautomer dominates, while the increase in the content of the keto tautomer (short-range PT) rises as a function of polarity of the solvent. In ethanol, due to specific solute–solvent stabilization through intermolecular hydrogen bonding, a substantial amount of the keto forms exists in solution. The irradiation leads to two competitive processes in the excited state, namely ESIPT and trans/cis isomerization around the azomethine bond as in other structurally similar Schiff bases. The studied compound is not suitable for bistable tautomeric switching, where long-range PT occurs, due to the difficult enolization of the coumarin carbonyl group. Full article

One of the modern trends in medicinal chemistry is the design of multifunctional drugs with a wide spectrum of actions. The main approaches to the creation of such drugs are the construction of new biologically active substances containing two or more pharmacophore groups in their structure or the introduction of an additional pharmacophore group into the molecule of a known drug. This work describes the synthesis of hybrid structures based on furan-2(3H)-ones and chromen-4(4H)-ones under the conditions of the Knoevenagel reaction. Various reaction conditions were screened. (E)-3-((2-oxo-5-arylfuran-3(2H)-ylidene)methyl)-4H-chromen-4-ones were obtained, and its structure was confirmed by ¹H and ¹³C NMR spectroscopy data. Based on NMR spectroscopy data, it was shown that the resulting compounds exist in the form of E-isomers. Full article

A fluorescent probe, N′-((3-methyl-5-oxo-1-phenyl-4, 5-dihydro-1H-pyrazol-4-yl) methylene)-2-oxo-2H-chromene-3-carbohydrazide (MPMC), was synthesized and characterized. Characterizations of the synthetic MPMC were conducted via proton nuclear magnetic resonance (¹HNMR) spectroscopy and carbon-13 nuclear magnetic resonance spectroscopy (¹³C NMR). The fluorescence emission behaviors of the MPMC probe towards diverse metal ions were detected, and the probe exhibited high sensitivity and selectivity towards Cu²⁺ over other metal ions via the quenching of its fluorescence. Furthermore, the existence of other metal actions made no apparent difference to the fluorescence intensity of the MPMC-Cu²⁺ system; that is, MPMC displayed a good anti-interference ability. Job’s plot of the MPMC and copper ions indicated that the detection limit was 10.23 nM (R² = 0.9612) for the assayed actions, with a stoichiometric ratio of 1:1 for MPMC and Cu²⁺. Additionally, the color of the MPMC probe solution changed from nearly colorless to yellow in the presence of Cu²⁺ in visible light, and the color change could be observed by the naked eye. Similarly, the color resolved from bright yellow into blue in ultraviolet light. Moreover, reusability studies indicated that the MPMC probe was reusable. The pH effect of the MPMC probe on Cu²⁺ had a broad range of pH detection, i.e., from 4.0 to 11.0. The response time of the MPMC probe for determining Cu²⁺ was within 1 min. The recognition of Cu²⁺ via MPMC performed on pre-treated paper under sunlight and UV light both had a distinct colour change. Thus, the solid-state method for detecting Cu²⁺ with the naked eye was both economical and convenient. Full article

Leishmaniasis is a group of infectious diseases caused by protozoan parasites that belong to the genus Leishmania. Currently, there is no human vaccine, and the available treatments are associated with toxicity, high cost, and the emergence of resistant strains. These factors highlight the need to identify new antileishmanial candidates. In this study, we synthesized twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments and evaluated their antileishmanial activity against the Leishmania braziliensis species, which is the main etiological agent responsible for American Tegumentary Leishmaniasis (ATL). The cinnamides were synthetically prepared using nucleophilic acyl substitution and copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reactions. The compounds were characterized using infrared, nuclear magnetic resonance, and high-resolution mass spectrometry techniques. We performed preliminary studies to evaluate the biological activity of these compounds against L. braziliensis promastigotes and axenic amastigotes. Compound 28, N-((1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-1H-1,2,3-triazole-4-yl) methyl)-3,4-dimethoxy cinnamide, demonstrated relevant antileishmanial activity with low toxicity in murine cells. The selectivity index values for this compound were superior compared with data obtained using amphotericin B. Furthermore, this cinnamide derivative reduced the infection percentage and number of recovered amastigotes in L. braziliensis-infected macrophages. It also induced an increase in reactive oxygen species production, depolarization of the mitochondrial potential, and disruption of the parasite membrane. Taken together, these findings suggest that this synthetic compound holds potential as an antileishmanial candidate and should be considered for future studies in the treatment of ATL. Full article

We hereby report a simple and efficient method for the preparation of 4-methylcoumarins series, including Coumarin 120 (7-amino-4-methylcoumarin) from phenols (or naphthols) and ethyl acetoacetate in the presence of 3 mol% InCl_3. Coumarins were obtained in good yields (52–92%) through Pechmann condensation, under a rapid and environmentally friendly protocol using a high-speed ball mill mixer at room temperature, with short reaction times, under solvent-free conditions. Full article