Search Results (23)

A novel dual-imidazoline ring quaternary ammonium salt corrosion inhibitor (TN-IM) was rationally synthesized via a three-step sequential reaction, using hydroxyethyl ethylenediamine and tetradecanedioic acid as starting materials, with benzyl chloride as the quaternizing reagent. The synthetic process involved amidation at 160 °C for 4 h, cyclization at 220 °C for 3 h, and quaternization at 70 °C for 3 h, respectively. Fourier transform infrared spectroscopy and proton nuclear magnetic resonance were employed to characterize the chemical structure of TN-IM, confirming its successful synthesis. The corrosion inhibition performance of TN-IM was evaluated by the static weight loss method and electrochemical measurements, while the corrosion products and surface morphology of N80 carbon steel were analyzed via energy-dispersive X-ray spectroscopy and scanning electron microscopy. Static weight loss tests conducted in 3.5 wt% of a NaCl solution saturated with 0.6 MPa CO₂ at 60 °C for 24 h revealed that TN-IM at a concentration of 0.15 mmol/L exhibited a corrosion inhibition efficiency 1.86% higher than that of a single-imidazoline ring quaternary ammonium salt inhibitor. Potentiodynamic polarization measurements demonstrated that TN-IM functions as a mixed-type corrosion inhibitor, with a predominant inhibitory effect on the anodic reaction on N80 steel. Electrochemical impedance spectroscopy results indicated that TN-IM molecules can adsorb onto the active sites of the N80 surface, thereby retarding the corrosion process by suppressing the charge transfer step in the electrochemical corrosion reaction. This study establishes a new paradigm for the synthesis of high-efficiency imidazoline-based CO₂ corrosion inhibitors with multiple adsorption sites, holding significant implications for corrosion control in harsh industrial environments. Full article

Brimonidine, a highly selective α₂-adrenergic receptor agonist originally developed for glaucoma treatment, has emerged as an important dermatological agent due to its potent vasoconstrictive and anti-inflammatory properties. This review summarizes its pharmacological characteristics, and clinical applications. By activating α₂-adrenergic receptors in cutaneous vessels, brimonidine induces rapid, reversible vasoconstriction and reduces neurogenic inflammation, leading to significant improvement of facial erythema in rosacea. Beyond its approved indication, topical brimonidine demonstrates efficacy in alcohol flushing syndrome, telangiectasia, post-procedural erythema, and as a local hemostatic agent in dermatologic surgery. Its favorable safety profile and minimal systemic absorption make it suitable for long-term use, though transient rebound erythema may occur. Advances in nanotechnology—such as supramolecular hydrogels and lipid-based carriers—enhance skin retention, prolong therapeutic action, and improve tolerability. These developments, together with ongoing synthesis of new quinoxaline–imidazoline analogues, open prospects for next-generation α₂-agonists with optimized selectivity and dermatologic applicability. Brimonidine’s emerging role extends to dermatologic formulations for transient redness and sensitive skin management. Integrating pharmacological, formulation, and molecular insights may transform brimonidine from a niche rosacea therapy into a versatile platform for vascular, inflammatory, and aesthetic skin treatments. Full article

Water-based drilling fluids (WBMs) are widely applied in petroleum engineering due to their lower cost and reduced environmental impact compared to oil-based muds. However, their performance is severely limited in shale formations, where hydration and swelling of clay minerals lead to wellbore instability. In this study, two novel imidazoline-type inhibitors were synthesized from fatty acids: A-Lin (derived from linoleic acid) and A-Lau (derived from lauric acid). The synthesis involved amidation followed by cyclization, and the products were characterized using FTIR and TGA. Their performance as shale hydration inhibitors was evaluated in WBM formulations and compared with commercial additives (Amine NF and Glycol). The FTIR spectra confirmed successful imidazoline ring formation, while TGA demonstrated good thermal stability up to 150 °C, with A-Lin exhibiting superior resistance due to its unsaturated structure. Rheological tests showed that the synthesized additives reduced plastic viscosity, thereby improving cuttings transport efficiency. Swelling tests revealed that A-Lin achieved the lowest final swelling (6.3%), outperforming both commercial inhibitors and the saturated A-Lau analogue. Furthermore, A-Lin provided the best lubricity coefficient (0.148), reducing torque and drag during drilling. Overall, A-Lin demonstrated strong potential as an efficient, thermally stable, and environmentally compatible shale inhibitor for advanced WBM formulations. Compared to conventional inhibitors such as KCl, glycol, and amine-based additives, A-Lin uniquely combines superior swelling inhibition, enhanced lubricity, and good thermal stability, highlighting its novelty as an imidazoline derivative derived from renewable fatty acids Full article

Imidazoline I₂ receptors (I₂-IR) are untapped therapeutic targets lacking a structural description. Although the levels of I₂-IR are dysregulated in a plethora of illnesses, the arsenal of ligands that can modulate I₂-IR is limited. In this framework, we have reported several new structural families embodying the iminophosphonate functional group that have an excellent affinity and selectivity for I₂-IR, and selected members have demonstrated relevant pharmacological properties in murine models of neurodegeneration and Alzheimer’s disease. Starting with these iminophosphonates, we continued to exploit their high degree of functionalization through a short and efficient synthesis to access unprecedented 2,3-di, 2,2,3-tri, 2,3,4-tri, and 2,2,3,4-tetrasubstituted diethyl (pyrrolidine-2-yl) phosphonates. The stereochemistry of the new compounds was unequivocally characterized by X-ray crystallographic analyses. Two selected compounds with structural features shared with the starting products were pharmacologically evaluated, allowing us to deduce the required key structural motifs for biologically active aminophosphonate derivatives. Full article

Background/Objectives: Recently, there has been great interest in metallopharmaceuticals as potential anticancer agents. In this context, presented studies aim to synthesize and evaluate of two copper(II) complexes derived from phthalazine- and imidazoline-based ligands against on three human cancer cell lines: cervix epithelial cell line (HeLa), breast epithelial-like adenocarcinoma (MCF-7), and triple–negative breast epithelial cancer cell line (MDA-MB-231), as well as non-tumorigenic cell line (HDFa). Moreover their antimicrobial, and antioxidant properties were assessed. Methods: The synthetized compounds—both free ligands L1, L2, L3 and copper(II) complexes C1 and C2—were characterized by elemental analysis, infrared spectroscopy. Additionally, a single-crystal X-ray diffraction studies we performed for free ligand L3 and its copper(II) complex C2. The stability of Cu(II)-complexes C1 and C2 was evaluated by UV-Vis spectroscopy. The cytotoxic potency of free ligands and their copper(II) complexes was estimated on HeLa, MCF-7, MDA-MB-231, as well as non-cancerous HDFa by use of an MTT assay after 48 h of incubation. Moreover, the antimicrobial activity of ligands L1 and L3 and their copper(II) complexes C1 and C2 was evaluated using reference strains of the following bacteria and yeasts: Staphylococcus aureus, Escherichia coli, and Candida albicans. The free radical scavenging properties of free ligands L1, L3 and the corresponding copper(II) complexes C1, C2 was tested with two colorimetric methods—ABTS, DPPH, and reduction ability assay (FRAP). Additionally, the ADME webtool was used to assess the drug-likeness of the synthesized compounds, as well as their physicochemical and pharmacokinetic properties. Results: Copper(II) complex C2 exhibited antitumor properties towards MDA-MB-231 compared with Cisplatin (cancer cell viability rate of 23.6% vs. 22.5%). At a concentration of 200 μg/mL, complexes C1 and C2 were less cytotoxic than the reference Cisplatin against a normal, non-cancerous skin fibroblast cell line (HDFa). According to in vitro tests, C2 reduced the viability of HeLa, MCF-7, and MDA-MB-231 cells by about 57.5–81.2%. It was evident that all compounds were devoid of antibacterial or antifungal activity. In vitro assays revealed that a moderate antiradical effect was observed for free ligand L1 containing phthalazin-1(2H)-imine in the ABTS radical scavenging assay (IC₅₀ = 23.63 µg/mL). Conclusions: The anticancer studies revealed that the most potent compound was copper(II) complex C2 bearing a phthalazin-1(2H)-one scaffold. None of the tested compounds showed antimicrobial or antifungal activity. This feature seems to be beneficial in terms of their potential uses as anticancer agents in the future. In vitro antiradical assays revealed that a moderate antioxidant effect was observed only for free ligand L1 containing phthalazin-1(2H)-imine. 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

Twenty 2-(4-alkyloxyphenyl)-imidazolines and 2-(4-alkyloxyphenyl)-imidazoles were synthesized, with the former being synthesized in two steps by using MW and ultrasonication energy, resulting in good to excellent yields. Imidazoles were obtained in moderate yields by oxidizing imidazolines with MnO₂ and MW energy. In response to the urgent need to treat neglected tropical diseases, a set of 2-(4-alkyloxyphenyl)- imidazolines and imidazoles was tested in vitro on Leishmania mexicana and Trypanosoma cruzi. The leishmanicidal activity of ten compounds was evaluated, showing an IC₅₀ < 10 µg/mL. Among these compounds, 27–31 were the most active, with IC₅₀ values < 1 µg/mL (similar to the reference drugs). In the evaluation on epimastigotes of T. cruzi, only 30 and 36 reached an IC₅₀ < 1 µg/mL, showing better inhibition than both reference drugs. However, compounds 29, 33, and 35 also demonstrated attractive trypanocidal activities, with IC₅₀ values < 10 µg/mL, similar to the values for benznidazole and nifurtimox. Full article

Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer’s disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I₂ receptors (I₂-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I₂-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature. We report the synthesis, the affinity in human I₂-IRs, the brain penetration capabilities, the in silico ADMET studies, and the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of this new bunch of I₂-IR ligands. Selected compounds showed neuroprotective properties and beneficial effects in an in vitro model of Parkinson’s disease, rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine, and showed crucial anti-inflammatory effects in a cellular model of neuroinflammation. After a preliminary pharmacokinetic study, we explored the action of our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 in a mouse model of AD (5xFAD). Oral administration of LSL33 at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment and synaptic plasticity, as well as reduced neuroinflammation markers. In summary, this new I₂-IR ligand that promoted beneficial effects in a well-established AD mouse model should be considered a promising therapeutic strategy for neurodegeneration. Full article

Searching for new alternatives for treating leishmaniasis, we present the synthesis, characterization, and biological evaluation against Leishmania amazonensis of the new ZnCl₂(H3)₂ complex. H3 is 22-hydrazone-imidazoline-2-yl-chol-5-ene-3β-ol, a well-known bioactive molecule functioning as a sterol Δ²⁴-sterol methyl transferase (24-SMT) inhibitor. The ZnCl₂(H3)₂ complex was characterized by infrared, UV-vis, molar conductance measurements, elemental analysis, mass spectrometry, and NMR experiments. The biological results showed that the free ligand H3 and ZnCl₂(H3)₂ significantly inhibited the growth of promastigotes and intracellular amastigotes. The IC₅₀ values found for H3 and ZnCl₂(H3)₂ were 5.2 µM and 2.5 µM for promastigotes, and 543 nM and 32 nM for intracellular amastigotes, respectively. Thus, the ZnCl₂(H3)₂ complex proved to be seventeen times more potent than the free ligand H3 against the intracellular amastigote, the clinically relevant stage. Furthermore, cytotoxicity assays and determination of selectivity index (SI) revealed that ZnCl₂(H3)₂ (CC₅₀ = 5 μΜ, SI = 156) is more selective than H3 (CC₅₀ = 10 μΜ, SI = 20). Furthermore, as H3 is a specific inhibitor of the 24-SMT, free sterol analysis was performed. The results showed that H3 was not only able to induce depletion of endogenous parasite sterols (episterol and 5-dehydroepisterol) and their replacement by 24-desalkyl sterols (cholesta-5,7,24-trien-3β-ol and cholesta-7,24-dien-3β-ol) but also its zinc derivative resulting in a loss of cell viability. Using electron microscopy, studies on the fine ultrastructure of the parasites showed significant differences between the control cells and parasites treated with H3 and ZnCl₂(H3)₂. The inhibitors induced membrane wrinkle, mitochondrial injury, and abnormal chromatin condensation changes that are more intense in the cells treated with ZnCl₂(H3)₂. Full article

The chemical synthesis of heterocycles typically requires elevated temperature and acid or base addition to form the desired product. Moreover, these reactions often involve hazardous reagents, which is why biocatalytic routes for heterocycle formation have gained increasing attention. In recent years, several enzymes belonging to the amidohydrolase superfamily have been identified to generate heterocycles via cyclocondensation reactions. Of particular interest is the amidohydrolase MxcM, which catalyzes the formation of an imidazoline moiety in the biosynthesis of the anti-inflammatory natural product pseudochelin A. In this study, we present a concept for the immobilization of this enzyme using a fused hexahistidine tag for fixation onto a solid, porous carrier. Notably, the immobilization improves the enzyme’s tolerance to organic solvents. The immobilized MxcM exhibits a residual activity of 169% in the polar solvent acetonitrile compared to the free enzyme, and the storage stability in the presence of 20 vol% acetonitrile was ameliorated. In addition, an immobilized enzyme reactor (IMER) was designed that can be operated under flow conditions. The MxcM-IMER retains its biocatalytic activity and mechanic stability over the tested operation time. These results provide important insights for the integration of heterocycle-forming amidohydrolases in chemical processes. Full article

The use of p53-MDM2/X inhibitors is a prospective strategy in anti-cancer therapy for tumors with wild type p53 protein. In our study, new low-molecular-weight inhibitors of the p53-mdm2 interaction have been proposed. The two-step synthesis of the imidazoline core with subsequent modifications for the nitrogen atom was carried out. New molecules caused the accumulation of p53 protein levels more than seven times than in comparison with the control. The accumulation of proapoptotic proteins such as p21 and PUMA has also been investigated, and the mechanism of cell death has been shown. Full article

As a continuation of our previous investigations aimed at the synthesis of novel nitrogen-containing heterocycles and their metal complexes, we have now prepared two series of compounds incorporating a phthalazine ring at the position C₂ of 4,5-dihydro-1H-imidazole. The starting phthalazine (I) in the reaction with 2-chloroimidazoline (II) gives rise to the formation of pseudobase III. Then, compound III upon treatment with HOSA yields betaine which under basic conditions gives 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV). In turn, the reactions of compound IV with a variety of acyl and sulfonyl chlorides lead to the formation of benzamides (V) and benzenesulfonamides (VI). Moreover, compounds V and VI can be transformed into corresponding 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one derivatives VII and VIII. Such ligands are susceptible to the reaction with CuCl₂ giving rise to the formation of corresponding copper(II) complexes: dichloro[2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine]copper(II) (1), dichloro[2-(1-benzoyl-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]copper(II) (2) and dichloro{bis-[2-(1-(phenylsulfonyl)-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]}copper(II) (3). The most promising results of biological studies were obtained for complex 1 towards the HeLa cell line (IC₅₀ = 2.13 μM) without a toxic effect against fibroblasts BALB/3T3 (IC₅₀ = 135.30 μM), which pointed towards its selectivity as a potential antitumor agent. It should be pointed out, that corresponding free ligand 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV) was less active than its metal complex (IC₅₀ = 87.74 μM). Full article

Mono-substituted imidazolin^X-2-iminato hafnium(IV) complexes (X = ⁱPr, ^tBu, Mesityl, Dipp) were synthesized and fully characterized, including solid-state X-ray diffraction analysis. When the X group is small (ⁱPr), a dimeric structure is obtained. In all the monomeric complexes, the Hf-N bond can be regarded as a double bond with similar electronic properties. The main difference among the monomeric complexes is the cone angle of the ligand, which induces varying steric hindrances around the metal center. When the monomeric complex of mono(bis(diisopropylphenyl)imidazolin-2-iminato) hafnium tribenzyl was reacted with three equivalents (equiv) of ⁱPrOH, the benzyl groups were easily replaced, forming the corresponding tri-isopropoxide complex. However, when BnOH was used, dimeric complexes were obtained. When five equivalents of the corresponding alcohols (BnOH, ⁱPrOH) were reacted with the monomeric complex, different dimeric complexes were obtained. Regardless of the high oxophilicity of the hafnium complexes, all complexes were active catalysts for the ring-opening polymerization (ROP) of ε-caprolactone. Dimeric complexes 5 and 6 were found to be the most active catalysts, enabling polymerization to occur in a living, immortal fashion, as well as the copolymerization of ε-caprolactone with rac-lactide, producing block copolymer PCL-b-LAC. The introduction of imidazolin-2-iminato ligands enables the tailoring of the oxophilicity of the complexes, allowing them to be active in catalytic processes with oxygen-containing substrates. Full article

In this paper, we have used a saturated five-membered N-Heterocyclic carbene (5SIDipp = 1,3-bis-(2,6-diisopropylphenyl)imidazolin-2-ylidine) for the synthesis of SNHC-haloboranes adducts and their further nucleophilic substitutions to put unusual functional groups at the central boron atom. The reaction of 5-SIDipp with RBCl₂ yields Lewis-base adducts, 5-SIDipp·RBCl₂ [R = H (1), Ph (2)]. The hydrolysis of 1 gives the NHC stabilized boric acid, 5-SIDipp·B(OH)₃ (3), selectively. Replacement of chlorine atoms from 1 and 2 with one equivalent of AgOTf led to the formation of 5-SIDipp·HBCl(OTf) (4) and 5-SIDipp·PhBCl(OTf) (5a), where all the substituents on the boron atoms are different. The addition of two equivalents of AgNO₃ to 2 leads to the formation of rare di-nitro substituted 5-SIDipp·BPh(NO₃)₂ (6). Further, the reaction of 5-SIDipp with B(C₆F₅)₃ in tetrahydrofuran and diethyl ether shows a frustrated Lewis pair type small molecule activated products, 7 and 8. Full article

The use of p53-MDM2 inhibitors is a prospective strategy in anti-cancer therapy for tumors expressing wild type p53 protein. In this study, we have applied a simple approach of two-step synthesis of imidazoline-based alkoxyaryl compounds, which are able to efficiently inhibit p53-MDM2 protein–protein interactions, promote accumulation of p53 and p53-inducible proteins in various cancer cell lines. Compounds 2l and 2k cause significant upregulation of p53 and p53-inducible proteins in five human cancer cell lines, one of which possesses overexpression of MDM2. Full article