Search Results (672)

Background/Objectives: Four novel thymol–benzimidazolium–chalcone hybrids were designed based on a molecular hybridization strategy that integrates bioactive scaffolds known for their antimicrobial and antioxidant properties. This approach aims to enhance biological activity through synergistic effects and multi-target interactions, as supported by previous studies on phenolic and benzimidazole derivatives. The inclusion of both antioxidant and antibacterial evaluations was motivated by the well-established role of oxidative stress in bacterial pathogenicity and resistance mechanisms. Methods: Their antibacterial potential was initially screened using the disk diffusion method and subsequently evaluated by determining MIC and MBC values against eight clinical Staphylococcus aureus isolates. Results: Among the tested compounds, compound 3a emerged as the most potent derivative, exhibiting MIC values ranging from 0.25 to 1 µg/mL. Morphological analysis confirmed significant disruption of bacterial cell integrity, and further investigation demonstrated strong antibiofilm activity accompanied by downregulation of key biofilm- and resistance-associated genes (icaA, dltB, and mepA). Molecular docking studies were performed against selected target proteins, including 1MWT, 3VSL, 3ZG5 (sortase A), and 2ZCS, which are associated with bacterial cell wall biosynthesis, DNA replication, virulence, and metabolic pathways. Compound 3a exhibited the highest binding affinity, with a docking score of −11.953 kcal/mol against 2ZCS. Conclusions: Overall, these findings highlight the potential of thymol-based benzimidazolium–chalcone hybrids as promising multifunctional agents with combined antibacterial, antibiofilm, and antioxidant properties. Full article

Chalcones featuring α,β–unsaturated carbonyl group are associated with an extensive range of pharmacological properties. The synthesized derivatives of benzimidazole–chalcone are prominent classes of bioactive compounds that have demonstrated significant applications. Recently, there has been an encouraged demand for synthesizing aromatic N–heterocyclic α,β–unsaturated hybrids that comprise benzimidazole–chalcones, which could be evaluated for activities against several diseases. The current review presents the synthetic approaches of the recently prepared benzimidazole–chalcone compounds and their biological applications. The biological activity studies include cytotoxicity against several cancer cells, antibacterial, antifungal, antileishmanial, antimalarial, antiviral and antidiabetic activities. The in silico studies of hybridized benzimidazole–chalcones are also discussed. Therefore, the review shows the significance of benzimidazole–chalcone derivatives and their potential as effective bioactive agents. Full article

This study reports the synthesis and characterization of a novel benzimidazole-derived Schiff base (BIMPB) via the condensation of (1H-benzo[d]imidazol-2-yl)methanamine with 1-phenylbutane-1,3-dione. The structure was confirmed using ¹H-NMR, ¹³C-NMR and FT-IR spectroscopy. Photophysical properties were extensively evaluated, revealing a strong S₀ → S₂ transition at 212 nm and fluorescence emission peaks at 396 and 410 nm, corresponding to π → π* and n → π* transitions. BIMPB demonstrated significant sensitivity to pH variations, exhibiting blue shifts of 11–23 nm across different environments. Furthermore, the compound acts as a fluorescent chemosensor for Cu²⁺ and Ca²⁺ ions, where coordination leads to a substantial reduction in fluorescence intensity accompanied by a distinct blue shift. The interaction between BIMPB and DNA was investigated using UV-Vis and fluorescence titration. The results showed a hypochromic effect and a minor shift in the absorption peak from 342 nm to 340 nm, suggesting a binding mechanism dominated by intercalation or electrostatic interactions. A high binding constant (K_b = 2.1 × 10⁵ M⁻¹) and a fluorescence quenching efficiency of 58.9% confirm the formation of a stable complex. Stern–Volmer analysis indicated a static quenching mechanism. These experimental findings, supported by molecular docking studies (binding energy = −8.3 kcal/mol), highlight the potential of BIMPB as a sensitive molecular probe for DNA-targeting and chemical sensing applications. Full article

Oxidative stress occurs when there is an excess of reactive oxygen species (ROS) in the cell, primarily produced by mitochondria. Excess ROS trigger membrane lipid peroxidation (LPO), cause mitochondrial swelling, and release proapoptotic proteins into the cytoplasm, which can lead to apoptosis. It is assumed that antioxidants that reduce excessive ROS formation by mitochondria can increase the body’s resistance to stress factors. We investigated the effects of hypoxia and the antioxidant Ambiol (2-methyl-4-dimethylaminomethylbenzimidazole-5-ol dihydrochloride) on the functional characteristics of mitochondria, which were assessed by measuring lipid peroxidation intensity using spectrofluorimetry, mitochondrial membranes fatty acid composition using chromatography, mitochondrial morphology using atomic force microscopy, and respiration rate using polarography. Injecting mice with Ambiol at a dose of 10⁻⁶ mol/kg for 5 days prevented the stress-induced activation of lipid peroxidation, a decrease in the unsaturation index of C₁₈ and C₂₀ fatty acids in mitochondrial membranes, and swelling of these organelles. The drug also increased the efficiency of oxidative phosphorylation during the oxidation of NAD-dependent substrates. Furthermore, Ambiol increased the lifespan of mice by 3.0–4.0 times under various types of hypoxia. Ambiol’s ability to maintain initial (control) levels of C₁₈ and C₂₀ unsaturated fatty acids appears to protect against stress-induced mitochondrial dysfunction. Full article

Background/Objectives: Protein kinases play a crucial role in cancer initiation, progression, and therapeutic resistance by regulating signalling pathways involved in tumour growth and survival. Consequently, they represent major targets in anticancer drug discovery. Among heterocyclic scaffolds explored in kinase inhibitor design, benzimidazole has emerged as a privileged structure due to its strong hydrogen-bonding capability and structural resemblance to purine moieties. Triazole motifs are also widely incorporated into bioactive molecules because of their metabolic stability, favourable electronic properties, and ability to establish key interactions within kinase active sites. This review aims to summarise and critically discuss benzimidazole- and triazole-based kinase inhibitors, both as individual scaffolds and as hybrid systems, with emphasis on their kinase targets and multitarget potential. Methods: The relevant literature was surveyed from major scientific databases focusing on studies describing the synthesis, biological evaluation, and molecular modelling of benzimidazole- and triazole-containing kinase inhibitors. Results: Numerous studies demonstrate that both benzimidazole and triazole scaffolds exhibit significant kinase inhibitory activity against oncogenic targets, including EGFR, cyclin-dependent kinases (CDKs), and components of the PI3K/Akt/mTOR signalling pathway. Hybrid molecules combining these pharmacophores frequently enhance binding interactions and facilitate the development of multitarget kinase inhibitors. Structure–activity relationship trends indicate that pharmacophore accessibility, substitution patterns, and linker architecture influence inhibitory potency and selectivity. Conclusions: Overall, benzimidazole- and triazole-based scaffolds represent promising platforms for developing next-generation multitarget anticancer agents and provide valuable insights for the rational design of improved kinase inhibitors. Full article

To address heavy metal contamination in wastewater, this study developed a novel chelating resin (PS-2-AB) by grafting 2-aminobenzimidazole onto chloromethylated polystyrene. The resin was characterized using SEM, BET, FTIR, and XPS to confirm successful modification and analyze its structural properties. Batch adsorption tests were conducted to evaluate its removal performance for Cu(II) and Ni(II) ions. Under optimal conditions (pH 5.0–7.0, dosage: 1.0 g/L), PS-2-AB achieved maximum adsorption capacities of 125.04 mg/g for Cu(II) and 157.44 mg/g for Ni(II), which are significantly higher than those of the commercial resin D113 (44.68 mg/g for Cu(II) and 25.17 mg/g for Ni(II)) under the same conditions. Adsorption kinetics followed the pseudo-second-order model, indicating chemisorption-dominated behavior, while equilibrium data fit the Langmuir model, suggesting monolayer adsorption. Thermodynamic parameters confirmed a spontaneous and endothermic process. After five regeneration cycles, PS-2-AB retained approximately 87% (Cu) and 89% (Ni) of its original capacity, demonstrating good reusability. These results indicate that PS-2-AB exhibits markedly better adsorption performance than D113, making it a promising and cost-effective adsorbent for the efficient removal of Cu(II) and Ni(II) from aqueous media. Full article

As a part of our research on the presence of conglomerates among the aryl benzyl sulfoxides, racemic-benzimidazolyl pentafluorobenzyl sulfoxide was synthesised, and its crystal structure was determined by a single crystal X-ray diffraction experiment. The main interactions building up the crystal structure were recognised and compared with those of similar compounds. Since the crystal structures of racemic and enantiopure benzimidazolyl pentafluorobenzyl sulfoxides are different, the presence of a conglomerate is excluded in the present case. Full article

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, is a severe zoonotic disease mimicking tumors, primarily affecting the liver with high mortality if untreated. Host immunity plays a pivotal role, shifting from Th1/Th17-mediated clearance to Th2/Treg-driven tolerance, enabling parasite survival. Liver macrophages, including Kupffer cells, polarize towards M2 phenotype under parasite antigens (e.g., phytic acid, exosomes), promoting immunosuppression, fibrosis, and T cell exhaustion via IL-10/TGF-β. This reshapes the tumor-like immune microenvironment with M2 macrophages recruiting Tregs, suppressing NK/DC functions, and fostering angiogenesis/fibrosis. Current treatment remains centered on surgery and benzimidazole therapy, both of which have notable limitations. Experimental immunomodulatory strategies, drug repurposing approaches, and targeted delivery systems may offer future therapeutic opportunities, but these concepts remain largely preclinical, unproven in AE, and require careful evaluation for safety and efficacy. Full article

Non-metallic hydride donors have emerged as an interesting, highly tunable class of compounds capable of CO₂ reduction, with benzimidazoles being simple, yet efficient and regenerable, representatives. In this work, the role of superbases as auxiliary groups attached to the benzimidazole framework was investigated using the CPCM(CH₃CN)/ωB97xD/aug-cc-pVTZ//CPCM(CH₃CN)/ωB97xD/6-31+G(d,p) approach. Three modes of operation were assessed through hydricity calculations and the modeling of two different CO₂ reduction mechanisms. Among the superbases considered, phosphazene substituents yielded the largest increase in the hydride donation ability, lowering hydricity by 6 kcal mol⁻¹ relative to 2-methylbenzimidazole, with the α-substitution exerting a stronger effect than β-substitution. For most systems, changes in hydricity correlate with changes in aromaticity, except in systems where steric congestion limits optimal substituent alignment. CO₂ activation pathways encompassing guanidine/CO₂ hydrogen bonding and guanidinium carboxamidine formation were modeled. In the former, transition state structures were significantly stabilized, and the overall exergonicity of the reduction is enhanced. Also, utilizing the longer and more flexible linker additionally decreases the barrier for the reaction. The carboxamidine pathway is disfavored because of the high stability of the carboxamidine intermediate and low barrier for the C–N bond cleavage, which reverses the mechanism to the reduction of isolated CO₂. Full article

New benzazole–sesamol derivatives 6a–8c were synthesized via an easily accessible reaction based on the coupling of Sesamol with in situ generated electrophilic N-alkoxycarbonylbenzazolium ions. This strategy successfully integrated benzothiazole, benzimidazole, and 5,6-dimethylbenzimidazole fragments with the biologically active natural lignan Sesamol. The structural integrity and the specific position of the newly formed C–C bond was confirmed by ¹H-, ¹³C{¹H}-, HSQC-NMR, FTIR, and HRMS analyses. The obtained compounds with yields in the range of 71–95% were evaluated for their in vitro radical scavenging activity and subjected to in silico predictions of mutagenicity and toxicity. Radical scavenging activity studies demonstrate that the introduction of a benzothiazoline ring (compounds 6a and 6b) enhances radical scavenging activity compared to Sesamol in the DPPH assay, outperforming the benzimidazole analogues. In silico analyses identified compounds 7b, 7c, 8a, 8b, and 8c as promising molecules due to the absence of mutagenic and irritant effects and their low toxicity profiles. In particular, compounds 7a, 7b, and 8a were found to be significantly safer than Sesamol. Compound 7a exhibited the highest safety profile, characterized by an LD₅₀ value of 3046.92 mg/kg. Full article

This study presents a quantitative investigation of substituent effects on the stability of 1:2 complexes formed between para-substituted 2-phenylbenzimidazole ligands and Cu(II) or Co(II) ions. The ligands, featuring hydroxyl (–OH), chloro (–Cl), and nitro (–NO₂) substituents, were synthesized via copper acetate-mediated oxidative cyclization. Stability constants (log K) were determined spectrophotometrically using both the Benesi–Hildebrand and Job methods, which yielded perfectly consistent results and confirmed ML₂ stoichiometry. For both metal series, the stability decreases in the order –OH > –Cl > –NO₂. Excellent linear correlations were obtained between log K and Hammett σ constants, yielding reaction constants of ρ = −0.79 for Cu(II) and ρ = −1.00 for Co(II). These negative ρ values confirm that electron-donating substituents enhance complex stability by increasing electron density on the donor nitrogen. Furthermore, the stability constants for Cu(II) complexes are approximately two orders of magnitude higher than those for Co(II), in agreement with the Irving–Williams series. This work establishes a clear, predictive structure–stability relationship and validates the combined methodological approach for quantifying metal–ligand interactions in tunable benzimidazole systems. Full article

This study presents a comparative thermal and kinetic analysis of three benzimidazole derivatives used in the pharmaceutical field: fenbendazole, mebendazole, and flubendazole. The investigations were carried out using thermoanalytical methods, including thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), in order to evaluate thermal stability, decomposition stages, and to calculate kinetic parameters. The obtained data were processed using isoconversional methods (Ozawa–Flynn–Wall, and Friedman) and non-parametric method (NPK) to determine activation energies and degradation mechanisms. The results revealed significant differences among the three compounds regarding their thermal stability and decomposition behavior, influenced by molecular structure and aromatic substituents. Furthermore, the comparative analysis provides valuable insights for optimizing technological processes, assessing stability in pharmaceutical formulations, and expanding research on the therapeutic potential of these compounds, including in oncological studies. Overall, the study contributes to a deeper understanding of the relationship between chemical structure and thermal stability in benzimidazole derivatives. Full article

A series of benzimidazole derivatives 6a–j was designed and synthesized via the condensation of the corresponding o-phenylenediamine intermediates with formic acid. Antibacterial activity was evaluated in vitro using the agar well diffusion method against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Klebsiella pneumoniae, with nitrofurantoin (300 µg/mL) as the positive control. Antifungal screening was performed against Aspergillus flavus, Penicillium duclauxii, and P. italicum at 20 and 50 µg/mL, with Amphotericin B as the reference drug at the same concentrations. Most compounds exhibited moderate to good antimicrobial activity. MIC determination identified 6h as the most active antibacterial agent (MIC = 5.0 µg/mL). The SEM analysis of bacteria treated with 6h revealed marked morphological damage, including cell deformation and membrane disruption, supporting a bactericidal mode of action. Collectively, these results highlight benzimidazole derivatives as promising scaffolds for the development of broad-spectrum antibacterial and antifungal agents. Full article

A DABCO-catalyzed one-pot synthesis of a novel pentacyclic heterocycle featuring an unprecedented benzo[4,5]imidazo[1,2-a]chromeno[3,2-e]pyridine scaffold from 2-(cyanomethyl)benzimidazole and 3-trifluoroacetyl-4-phenyl-4H-chromene has been developed. This hybrid architecture merges three privileged pharmacophores—benzimidazole, chromene, and pyridine—into a rigid, nearly planar π-extended system decorated with trifluoromethyl and nitrile groups. The structure of 8-phenyl-13a-(trifluoromethyl)-13aH-benzo[4,5]imidazo[1,2-a]chromeno[3,2-e]pyridine-6-carbonitrile was unambiguously confirmed through NMR spectroscopy and X-ray diffraction analysis. A plausible mechanism involves Michael addition, hemiaminal formation, ring opening, recyclization, and oxidation. Full article

Oxidative stress results from the excessive production of reactive oxygen species (ROS), which cause cellular and molecular damage and contribute to chronic diseases. Given the recognized antioxidant potential of benzimidazole derivatives—particularly 2-mercaptobenzimidazole—this study aimed to synthesize novel organosilicon S-silylalkylthioethers (I–IV) and N-alkylsilylthioethers (1a–3f) derived from this scaffold and to evaluate their antioxidant and antibrowning properties. The S-silylalkylthioethers were obtained by reacting 2-mercaptobenzimidazole with different chloroalkylsilanes under reflux in ethanol, followed by a reaction with alkyl halides in aprotic media at room temperature to prepare the N-alkylsilylthioethers. Structural elucidation was achieved through 1D and 2D NMR and FT-IR. Antioxidant activity was assessed using DPPH, the total antioxidant capacity, and ferric-reducing assays. The results showed several derivatives with notable antioxidant responses, revealing a clear relationship between carbon chain length, logP values, organosilicon substitution patterns, and radical-scavenging efficiency. Spearman correlation analysis further confirmed that DPPH activity is inversely related to total carbon number, molecular size, molecular weight, and LogP (ρ = −0.68 to −0.73, p < 0.001) and moderately negatively correlated with N-alkyl chain length (ρ = −0.47, p = 0.027), while S-alkyl chains showed no significant effect. These findings highlight the potential of these benzimidazole–organosilicon hybrids as antioxidant candidates and demonstrate how physicochemical properties govern their reactivity and antiradical capacity. Full article