Search Results (3,469)

Six 1,4-disubstituted pyrazoles linked to a benzenesulfonamide and a benzodioxane unit have been synthesized through a copper(I)-catalyzed formal [3+2] cycloaddition (32CA) reaction of alkynes with 3-arylsydnones. The Cu-catalyzed sydnone–alkyne cycloaddition (CuSAC) procedure has been optimized to promote the formation of the pyrazole ring and to deliver in three steps the six target compounds 5a–f, fully characterized by ¹H/¹³C-NMR and mass spectrometry (EIMS). Ten solvent conditions were evaluated. The reaction proceeded most efficiently in the presence of copper(II) sulfate pentahydrate in aqueous t-butanol in the presence sodium acetate, to reach a yield of 96%. The mechanism of the Cu(I)-catalyzed reaction has been studied within the Molecular Electron Density Theory (MEDT). This rection is a domino process that consists in a Cu(I)-catalyzed formal [3+2] cycloaddition followed of an extrusion of CO₂ yielding the final pyrazole. The capacity of heterocyclic compounds 5a–f to interact with human cyclophilin A (Cyp A), which is a host cofactor for hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1), and with the HIV-1 protein gp120-CD4 was evaluated using molecular docking. Compounds 5a,b,d,f showed a satisfactory protein binding capacity. The physicochemical and metabolic properties of the compounds were also evaluated in silico. These predictions provide important information to guide future design in this series of potential antiviral agents. Full article

Pyrrolo[2,3-d]pyrimidine is a privileged fused heterocyclic scaffold that has attracted considerable attention in medicinal chemistry due to its diverse biological activities. Herein, we report an efficient synthesis strategy for the preparation of the pyrrolo[2,3-d]pyrimidine-based natural toyocamycin aglycone and pyrrolo[2,3-d]pyrimidine derivatives. The synthesis of toyocamycin aglycone features a key benzylamine nucleophilic substitution followed by a palladium-catalyzed cyanation reaction. From a key intermediate derived from this route, nineteen new pyrrolo[2,3-d]pyrimidine derivatives were rapidly synthesized via key Suzuki–Miyaura coupling and amine nucleophilic substitution reactions. Their cytotoxic activities were evaluated against Huh-7 and HepG liver cancer cell lines. Most derivatives were inactive after 24 h. However, 28a–28c, 28e and 28f exhibited moderate cytotoxicity with IC₅₀ values ranging from 5.7 to 62.6 μM. Among them, compound 28e displayed the highest potency against HepG cells, with IC₅₀ values of 5.7 μM. Compared with normal HEK293 cells, it showed a selectivity index (SI) of 3.60 against HepG cells. Preliminary structure-activity relationship analysis suggested that incorporation of a cyclopropyl group further improves antitumor activity. 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

The objective of this study was to design and evaluate π-extended 1,8-naphthalimide derivatives as photoinduced electron transfer (PET) optical sensors for protons and metal cations, with emphasis on the role of heterocyclic annulation and receptor–chromophore electronic matching. Benzofuran- and benzodioxin-annulated naphthalimides bearing either a dimethylaminoethyl receptor or a non-donating alkyl substituent at the imide nitrogen were synthesized using tailored synthetic strategies. Their photophysical properties were investigated by absorption and fluorescence spectroscopy, while sensing performance was evaluated by fluorescence titrations. Quantum chemistry calculations were employed to rationalize experimental observations. Benzofuran-annulated derivatives exhibit structured π–π* absorption bands and strong fluorescence, whereas introduction of the receptor induces efficient fluorescence quenching via reductive PET. Protonation or metal ion coordination suppresses PET and leads to pronounced fluorescence enhancement, particularly in the presence of Cu(II) and Sn(II). In contrast, benzodioxin-annulated derivatives display intramolecular charge-transfer absorption bands, large Stokes shifts, and low fluorescence quantum yields in polar media, resulting in a negligible sensing response. Computational results attribute this behavior to an unfavorable energy arrangement of the donor–acceptor orbitals. Overall, the study demonstrates that heterocyclic annulation critically governs the electronic structure and sensing performance of naphthalimide fluorophores, providing guidelines for the rational design of PET-based optical sensors. Full article

6(5H)-phenanthridinone derivatives, as an important class of alkaloids, have broad application value in drug development and functional material synthesis. In this study, a nickel-catalyzed synthetic strategy was developed, using 2-bromobenzamide compounds as starting materials. Through an intermolecular cyclization reaction, a series of 6(5H)-phenanthridinone derivatives bearing amide substituents was efficiently constructed. The optimal reaction system was identified: Ni(acac)₂/Zn as the catalyst, PCy₃ as the ligand, toluene as the solvent, Cs₂CO₃ as the base, under an argon atmosphere at 150 °C for 12 h. The target products were obtained in yields up to 88%. Further substrate scope exploration demonstrated the excellent generality of this method, successfully synthesizing 21 derivatives with various substitution patterns, achieving yields ranging from 51% to 92%, and showing good compatibility with multiple functional groups such as alkyl, aryl, and heterocyclic moieties. Importantly, the reaction remained stable during gram-scale experiments, successfully yielding the desired compound at 85%. This work not only provides an approach for the precise construction of the 6(5H)-phenanthridinone framework but also opens an efficient pathway for the controlled synthesis of amide-substituted derivatives. Full article

Gold(I) complexes are particularly useful as catalysts in a variety of reactions including, in particular, the electrophilic activation of alkyne substrates, yet they generally require the addition of a silver salt to activate the gold complex by removing an anionic ligand. This results into higher costs and possible problems related to the non-innocence of the silver additive. In this contribution, we highlight the possibility to proficiently use a dinuclear monocationic gold(I) complex developed in our laboratory as a silver-free catalyst. The complex, featuring a bridging N-phosphanyl-N-heterocyclic carbene (NHCP) ligand, indeed exhibits notable activity and selectivity in standard alkyne hydroamination and hydroalkoxylation reactions, particularly in the case of internal alkynes and secondary aromatic amines as substrates. Full article

Reductive deuteration of N-heterocycles provides an efficient route to deuterated scaffolds, yet achieving controlled deuterium incorporation in quinoline remains challenging. Herein, we report a high-temperature H₂-treated Rh/TiO₂ catalyst (Rh/TiO₂–H500) that enables efficient reductive deuteration of quinoline using D₂O as a deuterium source. Structural characterization reveals that reduction at 500 °C induces a pronounced strong metal–support interaction (SMSI), leading to partial TiO_x encapsulation of Rh nanoparticles and interfacial electron transfer that generates electron-rich Rh⁰ species. This optimized interfacial structure promotes cooperative C–H activation and effective H/D transfer across the reduced quinoline framework, affording high deuterium incorporation at multiple positions of 1,2,3,4-tetrahydroquinoline (THQ). These results highlight the importance of SMSI-driven electronic and interfacial modulation in regulating reductive H/D exchange over heterogeneous catalysts. Full article

Background: Cancer patients are highly susceptible to microbial infections due to immune suppression, necessitating therapeutic strategies that integrate anticancer efficacy with effective antimicrobial intervention. Chalcone-derived nitrogen-fused heterocycles represent a promising platform for developing multi-target agents with relevance to antimicrobial drug delivery, particularly for localized infections. Methods: A series of chalcone-based pyrazoline-thiadiazole nitrogen-fused azole hybrids was synthesized via thiosemicarbohydrazide-functionalized intermediates and fully characterized. Antiproliferative activity was evaluated against MCF-7, HepG-2, HeLa, and HCT-116 cell lines, alongside selectivity toward WI-38 normal fibroblasts. Antibacterial, antibiofilm, and in vivo efficacy were assessed against methicillin-resistant Staphylococcus aureus (MRSA USA300) and Acinetobacter baumannii AB5057. Mechanistic investigations included cell-cycle analysis, apoptosis assays, ERK2, RIPK3, p53, BAX/Bcl-2 quantification, DNA gyrase inhibition, molecular docking, molecular dynamics simulations, and density functional theory calculations. Results: Compound 13 exhibited potent cytotoxicity, particularly against MCF-7 (IC₅₀ = 3.87 ± 0.2 µM), outperforming doxorubicin (IC₅₀ = 4.17 ± 0.2 µM), with high selectivity indices (SI = 10.7 for MCF-7). Mechanistically, compound 13 induced G₂/M arrest (40.16% vs. 14.15% control), increased apoptosis to 32.89%, up-regulated ERK2 (3.17-fold), RIPK3 (11.97-fold), and p53 (3.54-fold), and markedly increased the BAX/Bcl-2 ratio (~42-fold). Compounds 7 and 13 displayed bactericidal activity against MRSA and A. baumannii (MIC/MBC = 10 mg/mL), potent antibiofilm effects, and significant in vivo efficacy in an MRSA skin infection model. Compound 13 reduced bacterial load by ~5 log units, outperforming vancomycin. DNA gyrase inhibition (IC₅₀ = 17.10 ± 0.17 µM) and computational studies supported target engagement. Conclusions: Pyrazoline-thiadiazole-based nitrogen-fused azole hybrids, particularly compound 13, demonstrated quantifiable anticancer and antimicrobial efficacy with strong in vivo validation, supporting their potential as multi-target candidates relevant to antimicrobial drug delivery in infection-prone cancer patients. Full article

Photochromic diarylethene molecules are promising candidates for applications in optical data storage devices. However, many reported diarylethene compounds suffer from inefficiencies due to low photocyclization quantum yields or poor fatigue resistance. To address this issue, we have developed a highly efficient boron–nitrogen heterocycle-bridged diarylethene. The bulky boron–nitrogen heterocyclic ethene bridge blocks interconversion between parallel and anti-parallel conformations, yielding two separated rotamers. Evaluation of their photochromic properties demonstrated that the anti-parallel conformer exhibits a high photocyclization quantum yield (Φ_o-c, 89.2%), excellent thermodynamic stability at 298 K and moderate fatigue resistance in hexane. Furthermore, direct comparison with its isosteric carbonaceous analog revealed that incorporating the azaborine moiety into the diarylethene scaffold significantly enhances its photochromic performance. This work presents a strategy that employs azaborine chemistry for the development of potential diarylethene-based photoswitchable materials. Full article

Cancer is an alarming health concern and economic burden in both developed and developing countries. Recently, there has been a growing demand for new alternative medications with more effectiveness and fewer harmful effects. During the past decades, a set of chemotherapeutic agents has been developed to fight against a large spectrum of cancer types. Unfortunately, their use is associated with a high level of toxicity; they are expensive, also, and their deployment is restricted by the emergence of cellular resistance. Plant-based components are garnering attention due to their low toxicity, selectivity, efficiency, and ease of accessibility. Alkaloids are one of these targeted compounds. Indeed, they are a highly diverse group with basic heterocyclic nitrogen-containing alkaloids that exhibit potent anticancer effects against a large panel of solid and liquid tumors, such as lung, breast, leukemia, liver, and colon cancer. The main molecular mechanisms involved in alkaloids’ anticancer effect are the induction of apoptosis via the extrinsic and intrinsic pathways, DNA damage, and the inhibition of cell cycle progression. Amazingly, these auspicious compounds exhibited strenuous inhibitory effects against a whole range of key enzymes involved in cancer progression and metastasis, such as Cytochrome P450 (CYP450), Cyclooxygenase-2 (Cox-2), Lysine-Specific Demethylase 1 (LSD1), Poly [ADP-ribose] polymerase (PARP), and topoisomerase, mainly through two action modes, namely irreversible and reversible inhibition. Furthermore, several conventional extraction methods have been developed to extract bioactive compounds from natural matrices, such as Soxhlet and hot water extraction. However, these techniques have many drawbacks, as they require a large amount of organic solvents, which not only affect human health but also generate severe environmental issues. To overcome these limitations, multiple eco-extraction techniques have emerged as potential alternatives to traditional extraction methods such as ultrasonic extraction, microwave-assisted extraction, and supercritical fluid extraction. In fact, they are considered eco-friendly and efficient technologies with less time and solvent consumption. Overall, this review aims to provide an updated overview of the most prominent anticancer alkaloids that have not been well reviewed already, as well as the main green extraction techniques relevant to the extraction of antineoplastic alkaloids. Full article

N-Heterocyclic carbene (NHC) catalysis has emerged as a powerful and versatile strategy for constructing silicon derivatives, offering a metal-free alternative to traditional transition-metal methods. This review comprehensively summarizes recent advances in the NHC-catalyzed synthesis of organosilicon derivatives. Key transformations discussed include both asymmetric and non-asymmetric silylation reactions, as well as the construction of silicon-stereogenic centers. The content is systematically organized according to the types of silicon products and their underlying catalytic mechanisms. Our own perspectives on future development within this rapidly evolving field are also outlined. Full article

Nitronyl nitroxides (NNs) are widely employed in chemistry, physics, and materials science due to their inherently high stability and magnetic properties. However, the synthesis of C(2)-organoelement derivatives remains a challenging task. This paper reports on the efficient synthesis and characterization of an unusual organosilver complex consisting of the [Ag–(IPr)₂]⁺ cation and the [Ag–(NN)₂]⁻ anion. The salt [Ag–(IPr)₂][Ag–(NN)₂] was prepared in high yields (88–96%) by two synthetic routes: by reacting the carbene ligand precursor IPr·HCl with Ag₂O and nitronyl nitroxide NN–H, or by addition of NN–H/^tBuONa to a THF solution of IPrAgCl (generated in situ from IPr·HCl and Ag₂O) under microwave irradiation. Electrochemical analysis of [Ag–(IPr)₂][Ag–(NN)₂] revealed a reversible one-electron oxidation peak at E_1/2 = −0.258 V and an irreversible reduction peak at E_p = −2.169 V, which is likely related to the electrochemical transformation of the nitronyl nitroxide moieties. Crystallization from an acetone/benzene solution yielded crystals of [Ag–(IPr)₂][Ag–(NN)₂]·2H₂O solvate, in which the diradical anion [Ag–(NN)₂]⁻ is bound to two water molecules by hydrogen bonds. These hydrogen bonds stabilize a planar conformation of the [Ag–(NN)₂]⁻ anion, in which both NN fragments lie in the same plane and, according to DFT calculations, are linked by fairly strong antiferromagnetic interaction. DFT calculations also predict the dissociation of the complex with water in toluene solution and a conformational change leading to the appearance of about 90° between NN fragments and a significant decrease in exchange interaction. Full article

(1) Background: Gastric cancer (GC) remains a major global health challenge due to its high heterogeneity and aggressive progression. The discovery of novel bioactive molecules with anticancer properties has, therefore, become a critical research focus. In this study, we synthesized and characterized 4,4′-(5,8-dioxa-2,11-diazadodecane-1,11-diene-1,12-diyl)diphenol (DODP) and evaluated its anticancer potential using molecular docking, bioinformatics, and experimental analyses. (2) Methods: The chemical structure of DODP was confirmed through ¹H and ¹³C NMR spectroscopy. Molecular docking was conducted to examine the interaction of DODP with apoptosis and cell cycle-related proteins (TP53, MDM2, and MYC) and the immune checkpoint marker CD274 (PD-L1). Cytotoxicity against AGS GC cells was determined using the MTT assay at concentrations ranging from 0.01 to 50 µM, and gene expression alterations were analyzed by quantitative polymerase chain reaction (qPCR) and bioinformatics evaluation. (3) Results: NMR data verified the successful synthesis of DODP. The docking results indicated strong binding affinity, especially with TP53 and CD274. DODP showed notable cytotoxicity after 72 h of exposure and induced upregulation of TP53, MYC, and CD274 and downregulation of MDM2 in AGS cells. Although the patterns were consistent with cell-based and bioinformatic analyses, significant discriminatory ability in blood samples was observed only for MYC (AUC = 0.651; p = 0.044). (4) Conclusions: DODP influenced apoptosis-associated transcriptional responses in GC, offering early mechanistic evidence that should be evaluated in more comprehensive biological models. Full article

We report a straightforward and versatile synthetic route to pyridinium-fused 1,3-selenazoles via the electrophilic cyclization of 2-pyridylselenyl chloride with alkynes. The reaction proceeds efficiently under mild conditions with representative terminal and internal alkynes. While the cyclization exhibits high regioselectivity favoring the 3-substituted isomer for most substrates, reactions with 2-pyridyl- and 2-quinolylacetylenes yield regioisomeric mixtures. DFT calculations rationalize this divergence, revealing a competition between kinetic and thermodynamic control; the 3-isomer is kinetically favored, while the 2-isomer is thermodynamically stabilized by an ancillary chalcogen bond between the selenium atom and the pyridine nitrogen of the alkyne substituent. Molecular structures were confirmed by single-crystal X-ray diffraction, and the non-covalent interactions governing supramolecular assembly in the solid state were rigorously analyzed using MEP surfaces, the QTAIM, and NBO analysis. Antifungal evaluation identified several compounds with notable activity against phytopathogenic fungi, highlighting the potential of this novel heterocyclic scaffold in agrochemical applications. 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