Search Results (511)

Imidazole derivatives represent a privileged class of nitrogen-containing heterocycles that continue to attract considerable attention owing to their structural versatility, synthetic accessibility, and wide range of applications in medicinal chemistry, materials science, catalysxis, and corrosion inhibition. In recent years, significant efforts have been directed towards the development of efficient, sustainable, and experimentally simple synthetic methodologies for substituted imidazoles. This review summarizes and critically evaluates recent advances (mainly from 2021 onward) in the synthesis of imidazole derivatives, with particular emphasis on multicomponent reactions, especially the Debus–Radziszewski condensation. Catalyst-free protocols, organocatalysts, metal-based catalysts, nanocatalysts, and ionic liquids are systematically discussed and compared. In addition, alternative two- and three-component strategies that enable access to nonclassical substitution patterns are reviewed. The advantages and limitations of each approach are highlighted with respect to reaction efficiency, substrate scope, sustainability, and practical applicability. This review aims to serve as a comprehensive reference for synthetic chemists seeking rational strategies for the preparation of structurally diverse imidazole derivatives. Full article

Background/Objectives: Betanin (Bet), a natural compound, exhibits potent antioxidant and metabolic regulatory properties, yet its effect on cellular glucose utilization remains unclear. This study investigated, for the first time, the impact of Bet on glucose consumption and the activation of key carbohydrate–catabolic pathways in human erythrocytes. Methods: In vitro assays were performed to evaluate enzyme inhibition and activation. Human erythrocytes were incubated with Bet to assess glucose consumption. Enzyme activities were measured spectrophotometrically, and molecular docking was used to analyze binding interactions. Results: Our results demonstrate that Bet inhibits digestive enzymes in a dose-dependent manner, with maximal inhibition at 90 µg/mL for pancreatic lipase and 70 µg/mL for α-amylase, showing IC₅₀ values of 48.8 and 31.9 µg/mL, respectively, supported by strong binding affinities of −9.3 and −8.9 Kcal/mol. These interactions are stronger than those of orlistat (−6.9 Kcal/mol) and acarbose (−7.7 Kcal/mol). Bet also induced the activity of AMPK with an IC₅₀ of 1.83 µg/mL and a BE of −7.90 Kcal/mol, compared to the specific AMPK activator A-769662, which had an IC₅₀ of 1.29 µg/mL and a binding energy of −10.0 Kcal/mol. Consequently, Bet stimulated key glycolytic enzymes, reaching maximal activation (~62%) at 1.4 µg/mL for hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6PD), and at 1.6 µg/mL for pyruvate kinase (PK), supported by binding energies of −7.2, −7.5, and −9.0 Kcal/mol and AC₅₀ values of 0.87, 0.98, and 0.91 µg/mL, respectively. Moreover, Bet enhanced key Krebs cycle enzymes (IDH, SDH, MDH, LDH) in a dose-dependent manner, with AC₅₀ values of 0.76, 0.80, 0.72, and 0.52 µg/mL and strong binding energies (−7.8, −7.8, and −8.4 Kcal/mol), reaching maximal activation near 1.4 µg/mL. Bet also increased glucose consumption by human erythrocytes. Conclusions: Bet enhances glucose utilization by inhibiting digestive enzymes and activating intracellular metabolic pathways, suggest potential metabolic regulatory effects. Full article

Quinoline derivatives constitute a privileged class of nitrogen-containing heterocycles with extensive applications in medicinal chemistry, agrochemicals, materials science, and functional organic materials. Owing to their broad biological and industrial relevance, the development of efficient, selective, and sustainable synthetic methodologies for quinoline construction remains an active area of research. This review provides a comprehensive overview of recent advances in quinoline synthesis, with particular emphasis on catalytic strategies aligned with the principles of green and sustainable chemistry. Classical transformations, including the Friedländer, Skraup, and Povarov reactions, are revisited in the context of modern catalytic developments that improve reaction efficiency, substrate scope, selectivity, and environmental compatibility. Special attention is devoted to homogeneous and heterogeneous catalytic systems based on both platinum-group and earth-abundant transition metals, highlighting the growing importance of borrowing-hydrogen and acceptorless dehydrogenative coupling methodologies. Recent progress in nanocatalysis, photocatalysis, multicomponent reactions, ionic-liquid-mediated transformations, and metal-free protocols is also critically discussed. Furthermore, solvent-free processes, microwave-assisted synthesis, and recyclable catalytic systems are examined as practical approaches toward minimizing waste generation and energy consumption. Mechanistic aspects, catalytic design principles, substrate limitations, and sustainability metrics are evaluated throughout the review to provide a critical perspective on current methodologies. Collectively, the advances summarized herein demonstrate the rapid evolution of quinoline synthesis toward more atom-economical, environmentally benign, and operationally efficient processes, while also identifying future opportunities for the development of next-generation catalytic platforms for quinoline-based heterocycle construction. Full article

1,5-Benzodiazepin-2-one is a significant class of heterocyclic compounds that have attracted considerable attention due to these versatile scaffolds and their multifunctional properties. Owing to the presence of a fused benzene–diazepine core, these compounds display rich chemical reactivity and various physicochemical characteristics, making them valuable structures in both fundamental and applied research. This review provides a comprehensive and critical overview of the advances reported to date on 1,5-benzodiazepin-2-ones, with particular emphasis on their diverse synthetic methodologies, reaction mechanisms, and structure–property relationships. Classical and modern synthetic approaches are discussed, including condensation reactions, multicomponent processes, catalytic and green chemistry approaches, as well as recent developments toward more sustainable and efficient protocols. The intrinsic reactivity of the 1,5-benzodiazepin-2-one framework enables access to structurally diverse derivatives. Furthermore, the review summarizes the broad range of applications of these heterocycles, especially in medicinal chemistry, where they have demonstrated significant biological activities, as well as in corrosion inhibition and photoluminescent materials. Finally, current challenges, limitations, and future perspectives are outlined to provide guidance for further research and development of 1,5-benzodiazepin-2-one-based systems. Full article

Azolium-derived metallates are well-established intermediates in metal–N-heterocyclic carbene chemistry; however, their potential as standalone therapeutic agents remains largely unexplored. Herein, we report the first systematic biological investigation of a diverse family of Au(I), Cu(I), Pt(II), Pd(II), and Ru(II) metallates paired with functionalized azolium cations. The complexes were synthesized quantitatively through a simple, atom-economical, and purification-free protocol under aerobic conditions in technical-grade green solvents. Structural characterization by multinuclear NMR spectroscopy and single-crystal X-ray diffraction confirmed metallate formation and enabled the first isolation and crystallographic characterization of unprecedented azolium-derived ruthenates. The antiproliferative activity of the complexes was evaluated against cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines, alongside non-cancerous MRC-5 fibroblasts. Backbone-functionalized derivatives emerged as the most potent compounds, displaying activities comparable or superior to cisplatin in A2780 cells and up to 1000-fold higher potency in the resistant A2780cis model. Notably, unlike cisplatin, the metallates retained nearly unchanged IC₅₀ values across both ovarian cancer lines, strongly suggesting resistance-evasive mechanisms of action. While benzylazido- and methyl guanosine-derived complexes generally exhibited lower overall potency, several members retained significant activity in resistant cells while showing markedly reduced toxicity toward normal fibroblasts, highlighting promising selectivity profiles. Ethoxide-functionalized derivatives and platinum-based metallates combined pronounced anticancer activity with favourable therapeutic windows. Overall, this work establishes azolium-derived metallates as a previously overlooked class of metal-based anticancer agents combining exceptional synthetic accessibility, broad structural tunability, and remarkable activity against platinum-resistant ovarian cancer. Full article

Nitrogen-containing molecules are fundamental components of astrobiology and play a key role in planetary environments. These species are particularly important because they may serve as key precursors to prebiotic molecules and contribute to chemical complexity. Reactions involving the highly reactive species methylidyne (CH) play a key role in complex organic formation in astrochemical environments, yet their interactions with nitriles such as acetonitrile (CH₃CN) remain relatively unexplored. In this work, we investigate the reaction network of CH + CH₃CN using high-level quantum-chemical calculations with RRKM and microcanonical transition-state theories to characterize the relative energies of reactants, intermediates, transition states, and products to identify the most favorable reaction pathways. Our results reveal that the most energetically favorable reaction channels proceed via barrierless CH addition to the triple CN bond and three-membered ring opening or CH insertion into a C-H bond, followed by a hydrogen elimination to form acrylonitrile (C₂H₃CN). This route highlights an efficient pathway toward a molecule of astrobiological interest. Acrylonitrile is particularly significant due to its stability and dual functional groups, which enable molecular growth complexity, both in planetary atmospheres and on surfaces, under astrochemical conditions. In addition to acrylonitrile, we identified a few other competing channels leading to an isonitrile species, which emphasizes a previously unexplored aspect of isomerization chemistry in the atmospheric planetary science. These isonitrile products, while less abundant, provide insight to the diversity of nitrogen-containing molecules that may form in environments such as Titan’s atmosphere or the interstellar medium. In these environments, acrylonitrile may serve as a reactive precursor that facilitates cyclization and molecular growth, which enables the formation of nitrogen-containing polycyclic aromatic molecules and N-heterocycles. This, in turn, contributes to the emergence of larger, more complex organic species relevant to prebiotic chemistry and potential origin of life in our solar system. Full article

Controlling the arbovirus vector Aedes aegypti represents a growing public health challange, intensifying the search for alternatives to combat the mosquito. In this context, the present study aims to evaluate the larvicidal activity of essential oils from three Piper species and their mixtures, as well as their preliminary toxicity and in silico acetylcholinesterase (AChE) inhibitory potential. The essential oils and mixtures were characterized by GC–MS. The larvicidal activity test was performed against third-stage larvae, and a preliminary toxicity test was preformed against Artemia salina. The results showed that the oils had a high content of phenylpropanoids such as safrole, dillapiole, and eugenol, as well as their derivatives. The mixtures showed lower toxicity when compared to the pure oils. P. aduncum oil showed the highest larvicidal action (LC₅₀ = 26.2 µg/mL), followed by P. callosum (LC₅₀ = 53.2 µg/mL), while P. divaricatum had the lowest activity (LC₅₀ = 123.8 µg/mL). Among the mixtures, the combination of P. divaricatum and P. aduncum stood out for its synergistic effect. Molecular docking analyses suggested that phytoconstituents interact favorably with AChE, supporting a neurotoxic mechanism associated with enzyme inhibition. Thus, Piper essential oils and mixtures are promising alternatives for the control of A. aegypti. Full article

Ortho-quinone methides (o-QMs) constitute a class of highly reactive and versatile intermediates in organic synthesis, characterized by a unique polarized electronic structure that combines an electron-deficient quinoid ring with an exocyclic electrophilic methylene or alkylidene unit. This distinctive feature renders powerful C4 synthons capable of participating in a wide range of higher-order cyclization reactions. In particular, [4 + n] cyclizations involving o-QMs (e.g., [4 + 1], [4 + 2], and [4 + 3]) have emerged as effective strategies for the rapid construction of structurally complex carbocyclic and heterocyclic frameworks, many of which serve as privileged scaffolds in natural products and functional materials. This review provides a comprehensive overview of recent advances in this rapidly developing field, with a systematic discussion of reaction design, mechanistic insights, and synthetic applications across various [4 + n] cyclization modes. Furthermore, current challenges are critically evaluated, and future opportunities are proposed, particularly in the development of novel catalytic systems, asymmetric variants, and innovative o-QM precursors. Overall, this review aims to offer researchers a clear understanding of the state of the art in o-QM chemistry and to inspire further innovation in this dynamic area of organic synthesis. Full article

3,6-Dihydro-2H-pyran heterocyclic framework is one of the currently developed heterocyclic building blocks in both pharmaceutical chemistry and organic synthesis, but with significant challenges. To overcome these challenges, herein, we report a robust synthetic methodology of palladium-catalyzed carboetherification of alkenes with alkynols for accessing polyfunctionalized 3,6-dihydro-2H-pyrans under aerobic oxidative conditions. In particular, this synthetic approach features excellent functional group compatibility, mild reaction conditions, and good step- and atom-economy. Additionally, an array of functional groups such as halogen group, ester, nitrile, aldehyde, phenoxy, and aromatic heterocycles were nicely tolerated, affording the synthetically challenging 2H-pyran derivatives in moderate-to-good yields. Notably, the practicability of this protocol is further verified by gram-scale synthesis and the late-stage diversification of pharmaceuticals and biologically active molecules. Full article

Background: Neglected diseases caused by protozoan parasites remain a major public health burden, particularly in low- and middle-income countries. Among the chemical motifs explored in antiparasitic drug discovery, guanidine-containing compounds have attracted considerable attention due to their strong cationic character, high capacity for hydrogen bonding, and versatility in interacting with biological targets. Methodology: This review summarizes advances reported in the last decade regarding guanidine derivatives with activity against pathogens associated with Chagas disease, human African trypanosomiasis, Leishmaniasis, tuberculosis, toxoplasmosis, dengue and schistosomiasis. Results: Evidence gathered from synthetic, natural, and drug-repurposing studies indicates that the guanidine, guanidine-containing and guanidine-related compounds contribute to modulating biological activity by changing electrostatic interactions, hydrogen-bonding networks, and physicochemical properties, with enzymes, nucleic acids, and membrane-associated targets essential for parasite survival. Across the analyzed studies, several emerging structure–activity relationship trends were identified, including the contribution of polycationic or dicationic architectures, the influence of halogenated or lipophilic substituents, and the dependence of biological activity on the complete molecular framework, including heterocyclic systems, macrocycles, peptide conjugates, hybrid scaffolds, and repurposed drugs. In addition to direct antiparasitic effects, certain guanidine-containing and guanidine-related compounds demonstrate immunomodulatory or host-protective properties, expanding the therapeutic relevance of this class. Despite promising in vitro results, protonation trapping, efflux pump susceptibility, and pharmacokinetic limitations such as poor oral absorption, high polarity, plasma protein binding and limited membrane permeability remain significant challenges for clinical translation. Nonetheless, the integration of medicinal chemistry, computational modeling, and biological screening continues to accelerate the identification of optimized scaffolds. Conclusions: Overall, guanidine-based compounds constitute a promising scaffold for the development of new therapeutic strategies targeting neglected parasitic diseases, and further structural optimization may enable the emergence of candidates with improved efficacy, selectivity, and drug-like properties. Full article

In the present study, a series of isoxazole derivatives were severally evaluated for their antifungal activity against the yeast Candida albicans and molds such as Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum. The results demonstrate that the isoxazole derivatives exhibit considerable antifungal potential, particularly isoxazole-sulfonate ester 4b (Ar= 4-(Cl)C₆H₄, Ar′= 4-(CH₃)C₆H₄), which was found to be active with significant inhibition zones; the diameters of the C. albicans and F. oxysporum samples were measured at 17.00 ± 0.00 mm and 14.00 ± 0.00 mm, respectively. Furthermore, compounds 4a (Ar= 4-(CH₃)C₆H₄, Ar′= 4-(CH₃)C₆H₄), 4c (Ar: 4-(Cl)C₆H₄, Ar′: 4-(NO₂)C₆H₄) and 4d (Ar: 4-(Cl)C₆H₄, Ar′: 3-(Cl)-2-(OCH₃)C₆H₃) demonstrated MIC and MFC values of 20 µg/mL against C. albicans. In addition, the anti-hemolytic activity of these derivatives was evaluated. Compounds 4a, 4e (Ar: 4-(Cl)C₆H₄, Ar′: 3,4-(OCH₃)₂C₆H₃) and aroylisoxazole 3a (Ar: 4-(CH₃)C₆H₄) demonstrated a high degree of anti-hemolytic activity (>99%) at all concentrations evaluated (10, 15, and 20 mg/mL). Molecular docking and molecular dynamics studies over 200 ns revealed protein–ligand complexes to have high affinity and stability, which agrees with the experimental results. The compounds 4d, 4e, and 3a have shown significant interaction with the target proteins of C. albicans, A. flavus, and F. oxysporum, respectively. The results have revealed that the major interaction sites are hydrogen bonding, hydrophobic interactions, and the presence of a water molecule, especially with key residues like TYR_84, ASP_120, SER_90, and THR_89. The crystal structure of compound 4a was also obtained. Full article

The synthesis of heterocyclic compounds such as pyridines, quinazolinones and coumarins is a fundamental area of organic chemistry due to their wide application in the pharmaceutical and chemical industries, agro-industry, and other fields of modern technology. As these compounds are produced in large quantities and have significant industrial importance, the development of sustainable and environmentally friendly synthetic approaches has become a key objective of green chemistry. In this context, this review examines the principles, methods and applications of the sustainable synthesis of pyridines, quinazolinones and coumarins in deep eutectic solvents (DESs), a new class of solvents characterized by low volatility, non-toxicity, ease of preparation and recyclability, often from renewable sources. Special emphasis is placed on synthetic strategies that achieve reaction efficiency while reducing environmental impact, including processes without additional catalysts or with reusable catalysts. The paper provides a comprehensive overview of recent advances and highlights the potential of DESs as a viable alternative to conventional organic solvents in the synthesis of bioactive pyridine, quinazolinone and coumarin compounds. Full article

Background: This study investigated the effects of increasing levels of salinity on leaf phytochemical composition and the antioxidant, antidiabetic, and anti-obesity activities. Method: Three quinoa accessions grown under escalating NaCl treatments had their leaves exposed to various chemical analyses. Polyphenols, tannins, and flavonoids were among the phenolic substances whose concentrations were measured. The phenolic chemicals in the water extract were identified using HPLC-DAD-ESI-MS/MS. In vitro and in silico methods were used to measure anti-radical (DPPH), anti-alpha glucosidase, anti-alpha-amylase, and anti-lipase activities. Results: The results showed that water and ethanol, due to their polarity, were the most effective solvents for extracting phenolic compounds. Additionally, salt application led to a dose-dependent increase in total phenols (TPC), flavonoids (TFC), and tannins (CT) across all accessions. The accession DE-1 exhibited the highest contents with average values of 1453.03–4398.36 mg EGA/100 g DW, 322.7–1090.7 mg CAE/100 g DW, and 77.9–335.96 mg CAE/100 g DW of TPC, TFC, and Tannins, respectively. HPLC-ESI-DAD-MS/MS profiling of phenolic compounds led to identifying 18 constituents, including five major compounds (p-coumaric acid, caffeic acid, vanillic acid, p-coumaroyl hexose, and HHDP-galloyl glucose). Except for p-coumaroyl hexose and HHDP-galloyl glucose, which were extensively biosynthesized/accumulated in the salt-tolerant accession DE-1, the remaining phenolic compounds showed irregular evolution depending on accession and salt concentration. Moreover, ethanol and water extracts were evaluated for their anti-radical and enzyme-inhibitory activities. Conclusion: Salt-stressed DE-1 water extract showed strong antioxidant and enzyme inhibitory activities, indicating potential antidiabetic and anti-obesity effects. These activities were confirmed by in silico analysis. Full article

The synthesis of nitrogen-containing heterocycles remains a subject of significant interest due to their applications in medicinal chemistry and materials science. This paper describes the preparation of imidazo[1,2-a]pyridine using a catalytic system consisting of the deep eutectic solvent (DES) choline chloride (ChCl)–tartaric acid (1:2) and I₂ by reaction between 2-aminopyridines and chalcones (1,3-diphenylprop-2-en-1-ones). The proposed mechanism suggests the activation of the chalcone carbonyl by the DES, enhancing the polarization of the conjugated system which suffers electrophilic addition by I₂ to the C=C bond. The resulting intermediate undergoes a nucleophilic attack by 2-aminopyridine followed by cyclization and iodine-promoted oxidation and aromatization to yield the corresponding imidazo[1,2-a]pyridine products. The role of the DES is crucial, as it facilitates carbonyl activation through hydrogen bond interactions, stabilizes reactive intermediates, and promotes protonation–deprotonation steps, thereby eliminating the need for metal catalysts or toxic organic solvents. Theoretical calculations at the PM6 level of theory suggest that the DES acts as a catalyst in this reaction, due to the nature of its components enabling the development of more sustainable synthetic strategies. Full article

Pyrazole derivatives have emerged as an important class of heterocyclic compounds in anticancer research due to their structural versatility and broad spectrum of biological activities. This review provides a concise overview of recent advances in the development of pyrazole-based anticancer agents, with emphasis on synthetic strategies, structure–activity relationships, and molecular mechanisms of action. Common synthetic approaches, particularly condensation and cyclization reactions, have enabled the preparation of structurally diverse pyrazole derivatives for biological evaluation. Available evidence indicates that the type and position of substituents within the pyrazole scaffold markedly influence anticancer potency, selectivity, and target affinity. Reported compounds act through multiple mechanisms, including inhibition of cancer-related targets such as tubulin, epidermal growth factor receptor (EGFR), cyclin-dependent kinases (CDKs), Bruton tyrosine kinase (BTK), and deoxyribonucleic acid (DNA)-associated pathways, as well as induction of apoptosis and disruption of cell-cycle progression. Several pyrazole derivatives have shown promising activity in in vitro and in vivo models. Overall, the findings summarized in this review identify the pyrazole scaffold as a valuable platform for the design and optimization of novel anticancer agents and support its continued exploration in medicinal chemistry. Full article