Search Results (3,221)

Nitrogen-containing heterocycles are essential compounds in nature, and their structural and functional diversity inspired the synthesis of a wide range of derivatives with diverse applications as pharmaceuticals, agrochemicals, dyes, polymers, cosmetics, etc. Among them, N-fused heterocycles represent an important category, due to their high potential as biologically active agents. Pyrazolo[5,1-c][1,2,4]triazoles, a class of nitrogen heterobicycles, have multiple applications as dyes and pigments. Also, a number of compounds containing this structure have been investigated for their biological activities. All the main experimental results published in the literature (both articles and patents) regarding the latter are summarized in this review. Full article

A total of 24 novel steroidal derivatives were synthesized, including 1,3,4-thia(selena)diazolines and structurally unique spirothiadiazolines, obtained through intramolecular cyclization under standard acetylation conditions. This strategy was further extended to the construction of a novel dimeric compound bearing a thiadiazoline linker. Seleno- and thiosemicarbazone precursors were derived from various functionalized steroidal monomers and dimers via straightforward synthetic protocols. Key intermediates included aldehyde 7 and ketones 16, 19, and 24. Rotameric equilibria were observed in certain thiosemicarbazones, attributed to partial double-bond character in the N–CS bond. Cyclization yielded heterocyclic systems as epimeric mixtures, and in some cases, inseparable mixtures of isomers were obtained due to low diastereoselectivity. Full structural elucidation of epimeric pairs was achieved using 2D NMR and IR spectroscopy, with compounds 2, 3, 5, 11, 17, 27, 28a, and 28b further confirmed by single-crystal X-ray diffraction. Preliminary antiproliferative assays against human cancer cell lines revealed GI₅₀ values below 10 µM for compounds 21, 22, and 27. Full article

The synthesis of heterocyclic compounds has gained significant attention in organic chemistry due to their diverse pharmacological properties. However, traditional synthetic approaches often involve hazardous chemicals, high energy consumption, and tedious workup procedures, leading to environmental concerns and low yields. In response, green chemistry strategies have emerged, emphasizing safer and more sustainable alternatives. Among these, magnetic nanoparticle (MNP)-based catalysts have shown remarkable promise in facilitating one-pot multicomponent reactions (MCRs), offering enhanced catalytic efficiency, ease of recovery, and reusability. This article provides a comprehensive overview of multicomponent reactions (MCRs) for the construction of a wide range of heterocyclic scaffolds—including chromenes, pyrazoles, phenazines, triazoles, tetrazoles, xanthenes, furans, indoles, imidazoles, pyridines, pyrimidines, oxazoles, and acridine derivatives—catalyzed by magnetic nanoparticles under sustainable and environmentally benign conditions. This review highlights recent advances (2018–2024) in the development and application of modified magnetic nanoparticles for green multicomponent synthesis. Emphasis is placed on their structural features, catalytic roles, and benefits in eco-friendly organic transformations. Full article

Rhodanine derivatives, as a subtype of thiazolidin-4-ones, represent an important class of heterocyclic compound known for their broad spectrum of biological activities and practical applications. In this short note, the synthesis of a new compound, 5-[2-(4-chlorophenyl)-2-oxoethyl]-3-(4-hydroxyphenyl)-2-thioxo-1,3-thiazolidin-4-one, is described. The target molecule was synthesized via a thia-Michael addition followed by cyclocondensation. Its structure was confirmed by ¹H and ¹³C NMR spectroscopy and further supported by 2D NMR studies. Full article

Background: Heterocyclic compounds represent a key class of compounds in medicinal chemistry. Both benzimidazoles and pyrimidines are essential heterocycles in medicinal chemistry, with various therapeutic properties. Recent literature presents a series of hybrid heterocyclic compounds, as their medicinal properties are generally improved compared to those of single heterocyclic rings. Methods: A literature search was conducted across relevant scientific literature from peer-reviewed sources, using keywords, including “benzimidazole”, “pyrimidine”, “Biginelli”, “benzimidazole-pyrimidine hybrids”, “anticancer”, “antiviral”, “antimicrobial”, and “anti-inflammatory”. Results: In this review, benzimidazole–pyrimidine hybrids are reported as anticancer, antimicrobial, antiviral, anti-inflammatory, analgesic, antiulcer, antidepressant, anti-Alzheimer’s, or antioxidant agents, with activities even better than those of existing drugs. The IC₅₀ values for these anticancer hybrids are in the nanomolar range, which signifies potent anticancer agents. It can be mentioned here that the anticancer hybrid Abemaciclib, as a CDK4/6 inhibitor for the treatment of certain types of breast cancer, was approved in 2017. The antimicrobial activity of these hybrids proved especially potent against a broad variety of infections, with MIC values in the range of µM or even nM. Moreover, these hybrids exhibited good antiviral properties against SARS-CoV-2, HIV-1, and the hepatitis C virus. The hybrids also functioned as JAK3 inhibitors, COX-1 inhibitors, and MAO-A inhibitors. Conclusions: This review presents synthesis methods of benzimidazole–pyrimidine hybrids, their medicinal properties, and SAR studies reported in the last 20 years. For almost every therapeutic activity, SAR studies have revealed the essential presence of a substituent on the aromatic rings or between the two benzimidazole and pyrimidine nuclei. Full article

The expansion of the Alberta Oil Sands Region (AOSR) has increased the deposition of petroleum-derived chemicals into the surrounding environment. Among these, polycyclic aromatic compounds (PACs), including sulfur-containing heterocyclic hydrocarbons, have been detected in exposed local wildlife, yet the reproductive toxicity and genotoxicity of this suite of PACs remain largely unexplored. This study examined the effects of dibenzothiophene (DBT) and its alkylated congener, 2,4,7-trimethyldibenzothiophene (2,4,7-DBT), on estradiol (E2) synthesis and metabolism in granulosa cells (SIGCs). Cells were exposed to DBT or 2,4,7-DBT for 24 h at concentrations detected in AOSR wildlife tissues (0, 0.1, 1 and 10 nM). We measured the gene expression of markers involved in E2 synthesis, signaling and metabolism, E2 output via ELISA and E2 metabolite production via HPLC-MS/MS. Exposure to 2,4,7-DBT, but not DBT, shifted E2 metabolism towards 4-OHE2, a genotoxic E2 metabolite. DNA damage was assessed by γH2Ax expression, alongside DNA repair (Parp1) and survival markers (pAKT). Interestingly, both DBT and 2,4,7-DBT increased DNA damage and triggered apoptosis via a caspase-independent mechanism. Given the critical role of granulosa cells in steroidogenesis and fertility, these findings highlight the endocrine-disruptive effects of sulfur-containing heterocyclic PACs and their potential to compromise reproductive health in exposed mammals. Full article

The COVID-19 pandemic has prompted the scientific community to develop new weapons against the SARS-CoV-2 spike protein. The study of its mutations is important to understand how it interacts with human receptors and how to prevent a future pandemic. In this study, four mutations of the Omega variant, along with those from the SARS-CoV-1 and MERS variants, were analyzed in complex with the angiotensin-converting enzyme 2 (ACE2) receptor. In silico studies were carried out to demonstrate that these mutations affect the interaction with the compounds under investigation. The ligands studied are heterocyclic compounds previously considered as potential inhibitors. Our results show that these compounds interact well with the spike protein and provide insights into how mutations, especially in the RBD region, can lead to perturbations in ligand–protein interactions. Full article

Background: Third-generation aromatase inhibitors (CYP19A1) are the mainstay of treatment for estrogen-receptor-positive breast cancer. This is because estrogen is required for cancer growth in approximately 70% of patients with this condition. Although potent and effective, aromatase inhibitors induce resistance and secondary effects, requiring treatment to be discontinued. This clinical limitation highlights the need to search for new molecules. Previous studies have led to the identification of a set of indole sulfonamide molecules that exhibit interesting activity against aromatase. Methods: Phenyl and benzyl sulfonamide derivatives with alkylated heterocycles linked by short methylene bridges were designed and synthesized. The aromatase inhibition and cytotoxicity were tested through in vitro assays. Molecular docking and dynamic simulations evaluated the interactions with the aromatase enzyme, while a target fishing strategy linked to gene associations relevant to breast cancer helped to uncover other targets. Results: All of the non-steroidal inhibitors synthesized showed significant activity. Compounds 3 and 9 demonstrated IC₅₀ values in the low micromolar range and selective action against MCF7 breast cancer cells over healthy lines. Computational studies confirmed stable and favorable aromatase binding. Target fishing identified EGFR and PTK2B as additional potential targets for a multi-target therapeutic strategy. Conclusions: Compounds 3 and 9 outperform indole-based inhibitors in their potency and selectivity, revealing strong therapeutic potential. Their binding affinity and specificity support further development. EGFR and PTK2B may enable a broader, multi-target approach. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with limited effective therapeutic options due to late diagnosis, aggressive progression, and rapid development of drug resistance. In pursuit of novel treatments, this study reports the design, synthesis, and biological evaluation of a new series of topsentin derivatives, featuring a 1,2,4-oxadiazole core. The newly synthesized derivatives were screened for antiproliferative activity against multiple PDAC cell lines (SUIT-2, Patu-T, and PANC-1), identifying several compounds with potent growth-inhibitory effects, particularly on SUIT-2 and Patu-T cells. Further studies demonstrated that these compounds also significantly inhibited cell migration and reduced clonogenic potential, with IC₅₀ values in the micromolar range. The results suggest that these marine-inspired 1,2,4-oxadiazole derivatives effectively target key hallmarks of PDAC, including proliferation, migration, and colony formation, supporting their further development as promising candidates for overcoming drug resistance and metastatic progression in pancreatic cancer. Full article

Several approaches to the synthesis of risdiplam, a pharmacologically relevant pyridopyrimidinone derivative, have been recently reported. However, most of these routes rely exclusively on palladium-catalyzed, cross-coupling reactions and involve low-yielding intermediates, which limit their scalability and complicate impurity control. In this work, we present a five-step, straightforward route to risdiplam, utilizing ethyl 2,8-dimethylimidazo[1,2-b]pyridazine-3-carboxylate—an accessible and cost-effective building block previously developed by our research group—as a starting material. The key step involves construction of the 4H-pyrido[1,2-a]pyrimidin-4-one scaffold via a copper(I)-catalyzed heterocyclization reaction. This represents a novel and convenient protocol for the synthesis of 2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-7-fluoro-4H-pyrido[1,2-a]pyrimidin-4-one, which serves as a crucial intermediate in the final stages of risdiplam synthesis. The overall process allows us to obtain the target compound with a 20% total yield (from abovementioned starting material) and high purity (99.86%, by HPLC-UV), with a maximum level of unidentified impurities not exceeding 0.046%. The developed approach eliminates the use of palladium catalysis and chromatographic purification, offering a practical and scalable alternative for risdiplam production. Full article

Pyridine is a recalcitrant organic compound present in industrial wastewater that causes severe effects on the environment and the health of living beings, as it is considered a toxic, mutagenic, teratogenic, and carcinogenic agent. Therefore, this research explored the efficacy of a zinc oxide catalyst, doped with platinum nanoparticles and supported alumina through the precipitation method, for the photocatalytic degradation of pyridine using a fluidized bed reactor. A Box–Behnken experimental design was used to analyze the effect of the pH (4–10), the pyridine concentration (20–300 ppm), and the amount of catalyst (20–100 g). The X-ray diffraction (XRD) characterization results confirmed the hexagonal structure of the zinc oxide and the successful incorporation of platinum. Scanning electron microscopy (SEM) revealed a nano-bar morphology upon catalyst doping, favoring the photocatalytic activity. Pyridine removal of 57.7% was achieved under the following conditions: a pH of 4, 160 ppm of pyridine, and 100 g of catalyst. The process followed a pseudo-first-order model, obtaining the reaction constant k₁ = 1.943 × 10⁻³ min⁻¹ and the adsorption constant k₂ = 1.527 × 10⁻³ L/mg. The results showed high efficiency and stability of the catalyst in the fluidized bed reactor for pyridine degradation, especially under acidic conditions, representing a promising technological alternative for treating industrial wastewater contaminated with N-heterocycles such as pyridine. Full article

To investigate the impact of microencapsulation on the volatile organic compounds (VOCs) in Zanthoxylum oil, this study compared unencapsulated Zanthoxylum oil (ZO) with microencapsulated Zanthoxylum oil (MZO) using physicochemical analysis, sensory evaluation, and molecular sensory analysis. Sensory evaluation revealed significant differences in aroma attributes between ZO and MZO, whereas no notable differences were observed in numbing intensity or overall acceptability. Colorimetric analysis indicated significant distinctions between the two samples. Electronic nose (E-nose) analysis demonstrated a reduction in overall aroma intensity for MZO compared to ZO. Gas chromatography–mass spectrometry (GC–MS) identified 43 VOCs, including 22 compounds present in both samples, accounting for 46.8% of the total. Terpenes represented the predominant class in both ZO (69.7%) and MZO (68.2%). Comprehensive analysis based on odor activity value (OAV) and variable importance in projection (VIP) identified nine volatile compounds as key aroma contributors. Gas chromatography–ion mobility spectrometry (GC–IMS) detected 90 the volatile organic compounds (VOCs), with esters (30.38%) and heterocyclic compounds (10.42%) predominating in ZO, while esters (29.08%) and alcohols (26.12%) were predominant in MZO. Compared to ZO, MZO exhibited increased levels of alcohols (from 12.04% to 26.12%) and terpenes (from 1.39% to 3.53%), but decreased levels of acids (from 5.77% to 2.72%) and aldehydes (from 10.29% to 4.62%). This approach provides a comprehensive assessment of flavor quality before and after microencapsulation, offers a scientific basis for quality control, and facilitates the development and utilization of Zanthoxylum oil resources. Full article

Isoxazole-based molecules constitute a crucial category of heterocyclic compounds with wide-ranging applications across pharmaceutical development, advanced materials, and pesticide synthesis. Traditional synthetic approaches for isoxazole derivatives frequently encounter challenges such as extended reaction periods, severe operating conditions, and reliance on toxic solvents. As an eco-friendly alternative, sonochemistry has emerged as a promising approach for organic synthesis, offering enhanced reaction efficiency, reduced energy consumption, and improved yields. In this context, this review introduces the recent advancements in ultrasound-assisted strategies for the synthesis of isoxazole-scaffolds and their derivatives. Various methodologies are discussed, including multi-component reactions, catalytic systems, and solvent-free protocols. The integration of ultrasound not only accelerates reaction kinetics but also minimizes byproduct formation and enables the use of green solvents or catalysts. Key advantages such as shorter reaction durations, higher atom economy, and operational simplicity are emphasized. This work underscores the potential of sonochemical techniques to revolutionize isoxazole-based molecule synthesis, aligning with the principles of sustainable and green chemistry. Full article

In this study, a series of novel β-phenylalanine derivatives were synthesised and evaluated for their anticancer activity. The 3-(4-methylbenzene-1-sulfonamido)-3-phenylpropanoic acid (2) was prepared using β-phenylalanine as a core scaffold. The β-amino acid derivative 2 was converted to the corresponding hydrazide 4, which enabled the development of structurally diverse heterocyclic derivatives including pyrrole 5, pyrazole 6, thiadiazole 8, oxadiazole 11, triazoles 9 and 12 with Schiff base analogues 13 and series1,2,4-triazolo [3,4-b][1,3,4]thiadiazines 14. These modifications were designed to enhance chemical stability, solubility, and biological activity. All compounds were initially screened for cytotoxicity against the A549 human lung adenocarcinoma cell line, identifying N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxo-1-phenylpropyl]-4-methylbenzenesulfonamide (5) and (E)-N-{2-[4-[(4-chlorobenzylidene)amino]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1-phenylethyl}-4-methylbenzenesulfonamide (13b) as the most active. The two lead candidates were further evaluated in H69 and H69AR small cell lung cancer lines to assess activity in drug-sensitive and multidrug-resistant models. Schiff base 13b containing a 4-chlorophenyl moiety, retained potent antiproliferative activity in both H69 and H69AR cells, comparable to cisplatin, while compound 5 lost efficacy in the resistant phenotype. These findings suggest Schiff base derivative 13b may overcome drug resistance mechanisms, a limitation commonly encountered with standard chemotherapeutics such as doxorubicin. These results demonstrate the potential role of β-phenylalanine derivatives, azole-containing sulphonamides, as promising scaffolds for the development of novel anticancer agents, particularly in the context of lung cancer and drug-resistant tumours. Full article