Search Results (36)

Heterocyclic compounds have shown that they hold significant therapeutic activities, highlighting the importance of discovering and developing novel candidates against cancers, infections, and oxidative stress-associated disorders. In this study, we demonstrated the biological activity of our previously synthesized thiazolidinone derivatives (TZDs-1, 6, and 7). Furthermore, we synthesized and structurally characterized a new derivative (TZD-5) using IR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the presence of its key functional groups, namely, carbonyl and imine. Their antioxidant activity was assessed through the DPPH assay, with TZD-5 showing the most potent effect (IC₅₀ = 24.4 µg/mL), comparable to ascorbic acid, an effect attributed to the methoxy group introduced via N-alkylation. Cytotoxicity was evaluated using the MTS assay on normal (HFF-1) and cancerous (HepG2 and A549) cell lines at two time points: 24- and 48 h exposure. Our findings highlight clear differences in cytotoxicity and selectivity among the tested thiazolidinone derivatives. TZD-1 and TZD-6 demonstrated significant, dose-dependent cytotoxic effects on both cancerous (HepG2 and A549) and normal (HFF-1) cell lines, thus limiting their therapeutic potential due to insufficient selectivity. TZD-5 exhibited moderate selectivity with higher susceptibility for HepG2 cells compared to normal cells. Notably, TZD-7 showed the most favorable cytotoxic profile, demonstrating strong selective cytotoxicity toward cancer cell lines with minimal adverse effects on normal fibroblasts. Overall, the results highlight TZD-5 and TZD-7 as promising candidates for antioxidant and selective anticancer therapies. Full article

A novel Schiff base, (E)-4-acetyl-N-(4-hydroxy-3-methoxybenzylidene)aniline (abbreviated as ANHMA), was synthesized and characterized using infrared and ¹H- and ¹³C-NMR spectroscopies. Optical properties in different solvents were evaluated using UV-vis absorption spectroscopy. The compound is shown to exhibit both positive and negative solvatochromism with reversal occurring for solvents with E_T(30)~45 (e.g., DMSO). The solvatochromic behavior of the compound was found to be strongly dependent on the hydrogen bond abilities and polarizability of the solvent, the observed reversal in solvatochromism being explained by the change in the dominant solvent effects in non-polar and polar–aprotic solvents (H-bond acceptor ability of the solvent and polarizability) compared to polar–protic solvents (H-bond donor ability), according to the developed Catalán multiparametric solvatochromic model. In all freshly prepared solutions studied, the (E)-enol-imine tautomer of the compound was found to strongly predominate over the keto-amine tautomeric forms, the latter increasing their populations over time in the presence of H-bond donor/acceptor species. Irradiation of ANHMA with UV light (λ ≥ 311 nm) was also investigated in several solvents and shown to follow a general pattern, with the conversion of the (E)-enol-imine tautomer into the keto-amine forms in a solvent-mediated enol-imine/keto-amine tautomerism, and (Z)→(E) C=C isomerization between the keto-imine forms. The experimental results received support from an extensive series of calculations on the structure and UV-vis spectra of the relevant tautomeric/isomeric forms of the compound performed at the DFT(B3LYP)/6-311++G(d,p) level of approximation (including time-dependent DFT calculations and solvent consideration). Full article

Due to the promising characteristics of aminoguanidine Schiff bases, ongoing research focuses on synthesizing and characterizing different compounds of this class to establish structure–property relationships. However, the pronounced alkalinity of the aminoguanidine residue makes isolating its Schiff bases in neutral form challenging. In the reaction of salicylidene-aminoguanidine ([HL]NO₃) with a strong base (NaOH), the partially neutralized product of the formula [HL]NO₃∙L·H₂O was obtained in the form of single crystals. This compound could be considered a cocrystal in which protonated and neutral forms of the Schiff base coexist. Furthermore, the coordinating properties of [HL]NO₃ towards zinc and organotin were investigated, and instead of the expected crystals of complex compounds, a novel polymorph of the ligand was obtained. Additionally, the reaction of [HL]NO₃, NH₄VO₃ and salicylaldehyde was carried out to achieve the condensation of the free NH₂-group in the aminoguanidinium fragment, targeting a vanadium(V) complex with tetradentate ligand. However, a purely organic compound containing three salicylaldehyde residues and two imine groups, i.e., C₂₁H₁₈N₂O₃, was isolated. All the obtained compounds were characterized by elemental and spectroscopic analysis, conductometry and SC-XRD analysis. The data were compared to those of similar structures, and the results provide further insight into the properties of these compounds and their future investigation for potential usage. Full article

A novel hybrid compound—2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (5) was synthesized and converted into di-substituted sulfonamide derivatives 6a–o and phthalazine ring opening products—hydrazonomethylbenzonitriles 7a–m. The newly prepared compounds were characterized using elemental analyses, IR and NMR spectroscopy, as well as mass spectrometry. Single crystal X-ray diffraction data were collected for the representative compounds 5, 6c, 6e, 7g, and 7k. The antiproliferative activity of compound 5, sulfonyl derivatives 6a–o and benzonitriles 7a–m was evaluated on approximately sixty cell lines within nine tumor-type subpanels, including leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast. None of the tested compounds showed any activity against the cancer cell lines used. The antioxidant properties of all compounds were assessed using the DPPH, ABTS, and FRAP radical scavenging methods, as well as the β-carotene bleaching test. Antiradical tests revealed that among the investigated compounds, a moderate ABTS antiradical effect was observed for sulfonamide 6j (IC₅₀ = 52.77 µg/mL). Benzonitrile 7i bearing two chlorine atoms on a phenyl ring system showed activity in a β-carotene bleaching test (IC₅₀ = 86.21 µg/mL). Finally, the interaction AGE/RAGE in the presence of the selected phthalazinimines 6a, 6b, 6g, 6m, and hydrazonomethylbenzonitriles 7a, 7c–g, and 7i–k was determined by ELISA assay. A moderate inhibitory potency toward RAGE was found for hydrazonomethylbenzonitriles—7d with an electron-donating methoxy group (R = 3-CH₃O-C₆H₄) and 7f, 7k with an electron-withdrawing substituent (7f, R = 2-Cl-C₆H₄; 7k, R = 4-NO₂-C₆H₄). Full article

Bismine sodium salt (BSNa), a Schiff base with two sodium carboxylates, has shown promising electrochemical performance as an anode material. However, its synthesis involves toxic reagents and generates impurities, requiring significant solvent use for purification. This study introduces a novel synthetic method using sodium hydroxide as the sole reagent, which acts as both a base and Na source in the ion exchange step. With this procedure, we reduce the amounts of chemicals, diminish toxicity, improve the purity of the target compound, and use less solvent while maintaining comparable electrochemical performance. Additionally, the procedure is carried out under anhydrous conditions that avoid the undesirable hydrolysis of the imine linkages. In a previous report, the processing of the composite electrode was not established. In this article, we address this issue; the electrochemical performance, specifically the rate capability, is enhanced by processing the electrodes in laminate form rather than powder. As alternative to N-methyl-2-pyrrolidone (NMP), a common but disadvantageous solvent in laminate processing, other solvents were explored by testing acetone (DMK), methylisopropylketone (MIPK), and a DMK-NMP mixture. The remarkable electrochemical performance (specific capacity of 260–280 mAh/g, and capacity retentions higher than 84% at 1C (260 mA/g) remained consistent across these solvents. Furthermore, we investigated replacing copper with aluminum as the current collector to reduce costs and increase the energy density of the battery. While aluminum performed comparably to copper at low specific currents C/10 (26 mA/g), it showed a significant shift in the redox process potentials at higher specific currents. Full article

The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel N-benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine oxides 10a–d are reported herein. The nitrones 10a–d were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTS^•+ (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation). Nitrones 10b, 10c, and 10d, having the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, exhibited high interaction with DPPH (64.5–81% after 20 min; 79–96% after 60 min), whereas nitrone 10a with unfunctionalized phenyl group showed the lowest inhibitory potency (57% after 20 min, 78% after 60 min). Nitrones 10a and 10d, decorated with phenyl and 4-fluoro-3-methylphenyl motif, respectively, appeared the most potent inhibitors of lipid peroxidation. The results obtained from radical cation ABTS^•+ were not significant, since all tested compounds 10a–d showed negligible activity (8–46%), much lower than Trolox (91%). Nitrone 10c, bearing the 2,4-difluorophenyl motif, was found to be the most potent LOX inhibitor (IC₅₀ = 10 μM). Full article

A new class of spirocyclic imines (SCIs) has been theoretically investigated by applying a variety of quantum chemical methods and basis sets. The uniqueness of these compounds is depicted by various peculiarities, e.g., the incidence of planar six-membered rings each with two imine groups (two π bonds) and the incorporation of the isosteres carbon, silicon, or germanium spiro centers. Additional peculiarities of these novel SCIs are mirrored by their three-dimensionality, the simultaneous occurrence of nucleophilic and electrophilic centers, and the cross-hyperconjugative (spiro-conjugation) interactions, which provoke charge mobility along the spirocyclic scaffold. Substitution of SCIs with strong electron-withdrawing substituents, like the cyano group or fluorine, enhances their docking capability and impacts their reactivity and charge mobility. To gain thorough knowledge about the molecular properties of these SCIs, their structures have been optimized and various quantum chemical concepts and models were applied, e.g., full NBO analysis and the frontier molecular orbitals (FMOs) theory (HOMO-LUMO energy gap) and the chemical reactivity descriptors derived from them. For the assessment of the charge density distribution along the SCI framework, additional complementary quantum chemical methods were used, e.g., molecular electrostatic potential (MESP) and Bader’s QTAIM. Additionally, using the aromaticity index NICS (nuclear independent chemical shift) and other criteria, it could be shown that the investigated cross-hyperconjugated sila and germa SCIs are spiro-aromatics of the Heilbronner Craig-type Möbius aromaticity. Full article

Novel imine-tethering cationic surfactants, namely (E)-3-((2-chlorobenzylidene)amino)-N-(2-(decyloxy)-2-oxoethyl)-N,N-dimethylpropan-1-aminium chloride (ICS-10) and (E)-3-((2-chlorobenzylidene)amino)-N,N-dimethyl-N-(2-oxo-2-(tetradecyloxy)ethyl)propan-1-aminium chloride (ICS-14), were synthesized, and the chemical structures were elucidated by various spectroscopic approaches. The surface properties of the target-prepared imine-tethering cationic surfactants were investigated. The effects of both synthesized imine surfactants on carbon steel corrosion in a 1.0 M HCl solution were investigated by weight loss (WL), potentiodynamic polarization (PDP), and scanning electron microscopy (SEM) methods. The outcomes show that the inhibition effectiveness rises with raising the concentration and diminishes with raising the temperature. The inhibition efficiency of 91.53 and 94.58 % were attained in the presence of the optimum concentration of 0.5 mM of ICS-10 and ICS-14, respectively. The activation energy (E_a) and heat of adsorption (Q_ads) were calculated and explained. Additionally, the synthesized compounds were investigated using density functional theory (DFT). Monte Carlo (MC) simulation was utilized to understand the mechanism of adsorption of inhibitors on the Fe (110) surface. Full article

An increase in the yield of the main cereal crops in the context of global climate changes requires additional impacts on plants. Natural and synthetic plant growth regulators (PGRs) are used to increase plant productivity and reduce the injury level caused by abiotic stressors. There is a growing need for novel highly effective plant growth stimulants to exhibit their effects at low doses and to not pose an environmental threat or injury to the crop quality. The derivatives of sydnone imine (SI), a mesoionic heterocycle possessing a 1,2,3-oxadiazole core, have been used as medicines until now but have not been used for agricultural applications. Some SI derivatives have recently been found to exhibit PGR properties. Herein, we report on the study of the PGR potential of nine SI derivatives bearing variable substituents at N(3), C(4), and N6 positions of the heterocycle designed to disclose the “molecular structure-PGR activity” relationship in this family. The SI derivatives were used in a wide concentration range (10⁻⁹–10⁻⁴ mol/L) for a pre-sowing treatment of winter wheat (Triticum aestivum L., two cultivars) and maize (Zea mays L., two hybrids) seeds in germinating experiments. All compounds were found to affect the growth of the axial organs of germinants, with the growth-stimulating or -inhibitory effect as well as its rate being considerably different for wheat and maize and, in many cases, also for roots and shoots. In addition, a pronounced concentration dependence of the effect was disclosed for many cases. The features of the molecular structure of SIs affecting their growth-regulating properties were elucidated. Compounds 4, 6, 7, and 8, which had exhibited a growth-promoting effect in germinating experiments, were used at appropriate concentrations for pot experiments on the same crops. For all compounds, the experiments showed a stimulating effect on the growth of roots (up to 80%), shoots (up to 112%), leaf area (up to 113%), fresh weights of roots (up to 83%), and aerial parts of the plants (up to 87%) or only on some of these parameters. The obtained results show a healthy outlook for the use of SI derivatives as promoting agents for improving the growth of cereal crop plants. Full article

A series of novel 1-oxo-2,3,4-trisubstituted tetrahydroisoquinoline (THIQ) derivatives bearing other heterocyclic moieties in their structure were synthesized based on the reaction between homophthalic anhydride and imines. Initial studies were carried out to establish the anti-coronavirus activity of some of the newly obtained THIQ-derivatives against two strains of human coronavirus-229E and OC-43. Their antiviral activity was compared with that of their close analogues, piperidinones and thiomorpholinones, previously synthesized in our group, with aim to expand the range of the tested representative sample and to obtain valuable preliminary information about biological properties of a wider variety of compounds. Full article

The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol (HBMF) and its Co(III) and Cu(II) complexes. The metal complexes (C1–C4) were synthesized in 2:1 (HBMF: metal ion) and 1:1:1 (HBMF: metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized HBMF ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand’s reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich–Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound C4, with molecular formula C₂₇H₂₃Cl₂CoFN₅O₃ exhibited profound anti-proliferative activity against the EAC cell line with a significant IC₅₀ value of 10 µm when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of C4 on neovascularization was evaluated by stimulating the angiogenesis with rVEGF₁₆₅, which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg/kg of two doses and tumor parameters were evaluated. Full article

An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonates through the Pudovik-type reaction of dialkyl/arylphosphite with imines, obtained from 5-phenyl-1,3,4-oxadiazol-2-amine and aromatic aldehydes, under microwave irradiation. Five of them were hydrolyzed to lead to the corresponding phosphonic acids. Selected synthesized compounds were screened for their in vitro antiviral activity against the avian bronchitis virus (IBV). In the MTT cytotoxicity assay, the dose-response curve showed that all test compounds were safe in the range concentration of 540–1599 µM. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 µM) and the [(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 µM) strongly inhibited the IBV infectivity, indicating their high virucidal activity. However, virus titers from IBV-infected Vero cells remained unchanged in response to treatment with the lowest non-cytotoxic concentrations of synthesized compounds suggesting their incapacity to inhibit the virus replication inside the host cell. Lack of antiviral activity might presumably be ascribed to their polarity that hampers their diffusion across the lipophilic cytoplasmic membrane. Therefore, the interactions of 5f and 6a were analyzed against the main coronavirus protease, papain-like protease, and nucleocapsid protein by molecular docking methods. Nevertheless, the novel 1,3,4-oxadiazole-based α-aminophosphonic acids and α-amino-phosphonates hold potential for developing new hygienic virucidal products for domestic, chemical, and medical uses. Full article

In the search for novel anode materials for lithium-ion batteries (LIBs), organic electrode materials have recently attracted substantial attention and seem to be the next preferred candidates for use as high-performance anode materials in rechargeable LIBs due to their low cost, high theoretical capacity, structural diversity, environmental friendliness, and facile synthesis. Up to now, the electrochemical properties of numerous organic compounds with different functional groups (carbonyl, azo, sulfur, imine, etc.) have been thoroughly explored as anode materials for LIBs, dividing organic anode materials into four main classes: organic carbonyl compounds, covalent organic frameworks (COFs), metal-organic frameworks (MOFs), and organic compounds with nitrogen-containing groups. In this review, an overview of the recent progress in organic anodes is provided. The electrochemical performances of different organic anode materials are compared, revealing the advantages and disadvantages of each class of organic materials in both research and commercial applications. Afterward, the practical applications of some organic anode materials in full cells of LIBs are provided. Finally, some techniques to address significant issues, such as poor electronic conductivity, low discharge voltage, and undesired dissolution of active organic anode material into typical organic electrolytes, are discussed. This paper will guide the study of more efficient organic compounds that can be employed as high-performance anode materials in LIBs. Full article

Nanomaterials have been extensively used in several applications in the past few decades related to biomedicine and healthcare. Among them, nanogels (NGs) have emerged as an important nanoplatform with the properties of both hydrogels and nanoparticles for the controlled/sustained delivery of chemo drugs, nucleic acids, or other bioactive molecules for therapeutic or diagnostic purposes. In the recent past, significant research efforts have been invested in synthesizing NGs through various synthetic methodologies such as free radical polymerization, reversible addition-fragmentation chain-transfer method (RAFT) and atom transfer radical polymerization (ATRP), as well as emulsion techniques. With further polymeric functionalizations using activated esters, thiol–ene/yne processes, imines/oximes formation, cycloadditions, nucleophilic addition reactions of isocyanates, ring-opening, and multicomponent reactions were used to obtain functionalized NGs for targeted delivery of drug and other compounds. NGs are particularly intriguing for use in the areas of diagnosis, analytics, and biomedicine due to their nanodimensionality, material characteristics, physiological stability, tunable multi-functionality, and biocompatibility. Numerous NGs with a wide range of functionalities and various external/internal stimuli-responsive modalities have been possible with novel synthetic reliable methodologies. Such continuous development of innovative, intelligent materials with novel characteristics is crucial for nanomedicine for next-generation biomedical applications. This paper reviews the synthesis and various functionalization strategies of NGs with a focus on the recent advances in different biomedical applications of these surface modified/functionalized single-/dual-/multi-responsive NGs, with various active targeting moieties, in the fields of cancer theranostics, immunotherapy, antimicrobial/antiviral, antigen presentation for the vaccine, sensing, wound healing, thrombolysis, tissue engineering, and regenerative medicine. Full article

Reduced imine cage (RCC3) was covalently bonded to the surface of silica spheres, and then the secondary amine group of the molecular cage was embedded in non-polar C10 for modification to prepare a novel RCC3-C10@silica HPLC stationary phase with multiple separation functions. Through infrared spectroscopy, thermogravimetric analysis and nitrogen adsorption–desorption characterization, it was confirmed that RCC3-C10 was successfully bonded to the surface of silica spheres. The resolution of RCC3-C10@silica in reversed-phase separation mode is as high as 2.95, 3.73, 3.27 and 4.09 for p-phenethyl alcohol, 1-phenyl-2-propanol, p-methylphenethyl alcohol and 1-phenyl-1-propanol, indicating that the stationary phase has excellent chiral resolution performance. In reversed-phase and hydrophilic separation modes, RCC3-C10@silica realized the separation and analysis of a total of 70 compounds in 8 classes of Tanaka mixtures, alkylbenzene rings, polyphenyl rings, phenols, anilines, sulfonamides, nucleosides and flavonoids, and the analysis of a variety of chiral and achiral complex mixtures have been completed at the same time. Compared with the traditional C18 commercial column, RCC3-C10@silica exhibits better chromatographic separation selectivity, aromatic selectivity and polar selectivity. The multifunctional separation mechanism exhibited by the stationary phase originates from various synergistic effects such as hydrophobic interaction, π-π interaction, hydrogen bonding and steric interaction provided by RCC3 and C10 groups. This work provides flexible selectivity and application prospects for novel multi-separation functional chromatographic columns. Full article