Search Results (167)

Adamantane is known to have two different carbon environments, the C1-type (or bridgehead) and C2-type (or methylene bridge), serving as a foundation to explore the effects of boron substitution at these sites. Using DFT with B3LYP/6-31G(d), the structural, electronic, and optical properties of 37 boron-substituted isomers were investigated. The adamantane structure has rigid T_d symmetry with an average rC-C of 153.7 pm, which progressively transforms to C_3v and C₁ symmetry in heavily substituted isomers. Analysis of the neutral and ionic species reveals a critical transition from electron-donating to electron-accepting behaviour at tri-boron substitution, confirmed by both DFT and coupled cluster calculations (CCSD(T)/CC-pVDZ). C1 substitution narrows the HOMO–LUMO gap significantly, achieving a 56% reduction compared to 44.5% for C2 substitution in tetra-bora derivatives compared to adamantane. Optical properties [CAM-B3LYP/6-311G(d,p)] show systematic red shifting with increasing boron substitution, with absorption maxima moving from 146 nm in pristine adamantane to 423 nm (C1) and 277 nm (C2) in heavily boron-substituted derivatives (tetra-bora-adamantane). While C1 substitution leads to symmetry-forbidden transitions, C2 substitution maintains allowed transitions, offering more consistent optical behaviour. These findings provide important insight for the design of adamantane-based materials with tailored electronic and optical properties. Full article

Designing bifunctional catalysts for efficient hydroisomerization of phenanthrene to alkyl-adamantane is a great challenge for producing high-density fuels. Herein, a bifunctional Pt catalyst was fabricated by developing hierarchical H-MSY-T zeolites with an NOA-co strategy. The influence of different mesopore template agents on the hierarchical structure of H-MSY-T zeolite was investigated. Effective regulation of pore structure and acid distribution of zeolites was achieved by adjusting the templating agents. The block copolymer P123 promoted the formation of mesoporous structures via self-assembly with a large mesopore centered at 8 nm. Large mesoporous structure and suitable distribution of Bronsted acid boosted the hydroisomerization of phenanthrene. The highest alkyl-adamantane yield of 45.9 wt% was achieved on the Pt/MSY-P1 catalyst and a reaction network of hydroisomerization was proposed. This work provides guidance to design highly selective bifunctional catalysts for the one-step hydroconversion of tricyclic aromatic hydrocarbons into high-density fuels. Full article

In 2022, the number of mpox cases spiked worldwide, leading to a surge in scientific research on members of the Orthopoxvirus genus and the discovery of new compounds exhibiting anti-orthopoxvirus activity. This work is devoted to the synthesis of compounds containing an adamantane fragment and the evaluation of their activity against the vaccinia virus, offering a possible mechanism of the antiviral action of the synthesized agents. Among all the studied adamantane derivatives, three compounds (2, 4, and 12) were found to demonstrate the highest antiviral activity, with the most promising compound 2 (N-(adamantan-1-yl)isonicotinamide) having the lowest toxicity level with a selectivity index (SI) of 115. The pharmacophoric profiles of these compounds are similar to the pharmacophoric profile of tecovirimat, an inhibitor of the membrane viral protein p37. Analysis of the results of molecular modeling suggests that the investigated compounds can inhibit the vaccinia virus by suppressing the phospholipase activity of membrane viral protein p37. Full article

Porcine circovirus 3 (PCV3) is a small non-enveloped circovirus associated with porcine dermatitis and nephropathy syndrome (PDNS). It has occurred worldwide and poses a serious threat to the pig industry. However, there is no commercially available vaccine. PCV3 capsid protein (Cap) is an ideal antigen candidate for serodiagnosis. Here, a novel fully automated chemiluminescence enzyme immunoassay (CLEIA) was developed to detect antibodies (Abs) to Cap in porcine serum. Recombinant PCV3 Cap, self-assembled into virus-like particles (VLPs), was produced using baculovirus and coupled to magnetic particles (Cap-MPs) as carriers. Combined with an alkaline phosphatase (AP)–adamantane (AMPPD) system, Cap-Abs can be rapidly measured on a fully automated chemiluminescence analyzer. Under optimal conditions, a cut-off value of 31,508 was determined, with a diagnostic sensitivity of 96.8% and specificity of 97.3%. No cross-reactivity was observed with PCV1 and PCV2 and other common porcine pathogens, and both intra-assay and inter-assay coefficients were less than 5% and 10%, respectively. Prepared Cap-MPs can be stored at 4 °C for more than 6 months. Importantly, this CLEIA had a good agreement of 95.19% with the commercially available kit, demonstrating excellent analytical sensitivity and significantly reduced operating time and labor. A serological survey was then conducted, and showed that PCV3 continues to spread widely in South China. In conclusion, our CLEIA provides time and labor-saving, and a reliable tool for PCV3 epidemiological surveillance. Full article

Background/Objectives: Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. Methods: The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by ¹H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D₂O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. Results: The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. Conclusions: The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment. Full article

Despite progress in the high-pressure synthesis of nanodiamonds from hydrocarbons, the problem of controlled formation of fluorescent impurity centers in them still remains unresolved. In our work, we explore the potential of a new precursor composition, a mixture of adamantane with detonation nanodiamond, both in the synthesis of nanodiamonds and in the controlled formation of negatively charged silicon-vacancy centers in such nanodiamonds. Using different adamantane/detonation nanodiamond weight ratios, a series of samples was synthesized at a pressure of 7.5 GPa in the temperature range of 1200–1500 °C. It was found that temperature around 1350 °C, is optimal for the high-yield synthesis of nanodiamonds <50 nm in size. For the first time, controlled formation of negatively charged silicon-vacancy centers in such small nanodiamonds was demonstrated by varying the atomic ratios of silicon/carbon in the precursor in the range of 0.01–1%. Full article

The development of novel tools to tackle viral processes has become a central focus in global health, during the COVID-19 pandemic. The spike protein is currently one of the main SARS-CoV-2 targets, owing to its key roles in infectivity and virion formation. In this context, exploring innovative strategies to block the activity of essential factors of SARS-CoV-2, such as spike proteins, will strengthen the capacity to respond to current and future threats. In the present work, we developed and tested novel bispecific molecules that encompass: (i) oligonucleotide aptamers S901 and S702, which bind to the spike protein through its S1 domain, and (ii) hydrophobic tags, such as adamantane and tert-butyl-carbamate-based ligands. Hydrophobic tags have the capacity to trigger the degradation of targets recruited in the context of a proteolytic chimera by activating quality control pathways. We observed that S901-adamantyl conjugates promote the degradation of the S1 spike domain, stably expressed in human cells by genomic insertion. These results highlight the suitability of aptamers as target-recognition molecules and the robustness of protein quality control pathways triggered by hydrophobic signals, and place aptamer-Hytacs as promising tools for counteracting coronavirus progression in human cells. Full article

Background: Encapsulation of siRNA fragments inside liposome vesicles has emerged as an effective method for delivering siRNAs in vitro and in vivo. However, the liposome’s fluid-phospholipid bilayer of liposomes allows siRNA fragments to diffuse out of the liposome, decreasing the dose concentration and therefore the effectiveness of the carrier. We have previously reported that β-cyclodextrins formulated in liposomes help increase the stability of siRNAs in cell culture medium. Here, we continued that study to include α, γ, methyl-β-cyclodextrins and β-cyclodextrin-modified gold and selenium nanoparticles. Methods: We used Isothermal Titration Calorimetry to study the binding thermodynamics of siRNAs to the cyclodextrin-modified nanoparticles and to screen for the best adamantane derivative to modify the siRNA fragments, and we used gel electrophoresis to study the stabilization effect of siRNA by cyclodextrins and the nanoparticles. Results: We found that only β- and methyl-β-cyclodextrins increased siRNA serum stability. Cyclodextrin-modified selenium nanoparticles also stabilize siRNA fragments in serum, and siRNAs chemically modified with an adamantane moiety (which forms inclusion complexes with the cyclodextrin-modified-nanoparticles) show a strong stabilization effect. Conclusions: β-cyclodextrins are good additives to stabilize siRNA in cell culture medium, and the thermodynamic data we generated of the interaction between cyclodextrins and adamantane analogs (widely used in drug delivery studies), should serve as a guide for future studies where cyclodextrins are sought for the delivery and solvation of small organic molecules. Full article

A novel sandwich-type electrochemical aptasensor based on supramolecularly immobilized affinity bioreceptor was prepared via host–guest interactions. This method utilizes an adamantane-modified, target-responsive hairpin DNA aptamer as a capture molecular receptor, along with a perthiolated β-cyclodextrin (CD) covalently attached to a gold-modified electrode surface as the transduction element. The proposed sensing strategy employed an enzyme-modified aptamer as the signalling element to develop a sandwich-type aptasensor for detecting prostate-specific antigen (PSA). To achieve this, screen-printed carbon electrodes (SPCEs) with electrodeposited reduced graphene oxide (RGO) and gold nanoferns (AuNFs) were modified with the CD derivative to subsequently anchor the adamantane-modified anti-PSA aptamer via supramolecular associations. The sensing mechanism involves the affinity recognition of PSA molecules on the aptamer-enriched electrode surface, followed by the binding of an anti-PSA aptamer–horseradish peroxidase complex as a labelling element. This sandwich-type arrangement produces an analytical signal upon the addition of H₂O₂ and hydroquinone as enzyme substrates. The aptasensor successfully detected the biomarker within a concentration range of 0.5 ng/mL to 50 ng/mL, exhibiting high selectivity and a detection limit of 0.11 ng/mL in PBS. Full article

Cytoprotective and neurotoxic kynurenines formed along the kynurenine pathway (KP) were identified as possible therapeutic targets in various neuropsychiatric conditions. Memantine, an adamantane derivative modulating dopamine-, noradrenaline-, serotonin-, and glutamate-mediated neurotransmission is currently considered for therapy in dementia, psychiatric disorders, migraines, or ischemia. Previous studies have revealed that memantine potently stimulates the synthesis of neuroprotective kynurenic acid (KYNA) in vitro via a protein kinase A-dependent mechanism. Here, the effects of acute and prolonged administration of memantine on brain kynurenines and the functional changes in the cerebral KP were assessed in rats using chromatographic and enzymatic methods. Five-day but not single treatment with memantine selectively activated the cortical KP towards neuroprotective KYNA. KYNA increases were accompanied by a moderate decrease in cortical tryptophan (TRP) and L-kynurenine (L-KYN) concentrations without changes in 3-hydroxykynurenine (3-HK) levels. Enzymatic studies revealed that the activity of cortical KYNA biosynthetic enzymes ex vivo was stimulated after prolonged administration of memantine. As memantine does not directly stimulate the activity of KATs’ proteins, the higher activity of KATs most probably results from the increased expression of the respective genes. Noteworthy, the concentrations of KYNA, 3-HK, TRP, and L-KYN in the striatum, hippocampus, and cerebellum were not affected. Selective cortical increase in KYNA seems to represent one of the mechanisms underlying the clinical efficacy of memantine. It is tempting to hypothesize that a combination of memantine and drugs could strongly boost cortical KYNA and provide a more effective option for treating cortical pathologies at early stages. Further studies should evaluate this issue in experimental animal models and under clinical scenarios. Full article

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund’s adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1′-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation. Full article

Achillea cucullata is a perennial herbaceous plant that has a long history of medical use in many cultures. The present research focuses on the biological activity and therapeutic potential of A. cucullata, namely its antibacterial and anticancer properties. While previous studies have shed light on the cytotoxic and antibacterial capabilities of Achillea cucullata aerial parts, there is still a considerable gap in knowledge concerning the anticancer potential of leaf and flower extracts. A. cucullata’s leaves and flowers were extracted using methanol. The total phenolic and flavonoid contents were evaluated. The antioxidant, cytotoxic, and antibacterial properties were evaluated against both Gram-positive and Gram-negative bacteria. The Gas Chromatography–Mass Spectrometry (GC–MS) analysis of A. cucullata leaf and flower extracts showed numerous amounts of bioactive components, including carvacrol, a TBDMS derivative; 2-Myristynoyl-glycinamide, acetylaminobenzothiazol-2-yl)-2-(adamantan-1-yl); Isolongifolol; (3E,10Z)-Oxacyclotrideca-3,10-diene-2,7-dione; and 3-Heptanone, 5-hydroxy-1,7-diphenyl. The extract has a high level of phenols and flavonoids. Cytotoxicity studies found that A. cucullata leaves and flowers had dose-dependent toxicity against MCF-7 and HepG2 cancer cell lines, with flowers being more effective. Apoptotic genes (caspase-3, 8, 9, and Bax) were upregulated in treated MCF-7 and HepG2 cells, whereas anti-apoptotic genes (Bcl-xL and Bcl-2) were reduced. Antibacterial screening revealed significant activity against both Gram-positive and Gram-negative pathogens. Overall, the research highlights the varied therapeutic potentials of A. cucullata, adding to the knowledge of plant-derived extracts in lowering disease risks. Future research should concentrate on in vivo studies to assess the effectiveness and safety of these substances. Full article

Morocco is a significant botanical reservoir that boasts a wealth of raw materials with promising applications across various industrial sectors, notably in pharmaceuticals and food. The objective of this study was to assess the effectiveness of essential oils (EOs) derived from Laurus nobilis L. leaves originating from the Tanger (EOT) and Meknes (EOM) regions in combating Callosobruchus maculatus infection. The chemical compositions of these oils were examined using Fourier transform infrared (FTIR) spectroscopy and gas chromatography–mass spectrometry (GC-MS). The biological activity of the EOs was evaluated via repulsion and fumigation tests against C. maculatus at varying concentrations. FTIR analysis revealed distinct vibrational bands indicative of various chemical compounds. GC-MS analysis was used to delineate the major chemical constituents of the EOs. The three predominant compounds in the EOT were 1,8-cineole (37.64%), linalool (16.40%), and adamantane (12.00%), whereas 1,8-cineole (47.84%), toluene (17.60%), and α-phellandrene (8.44%) were the most abundant in the EOM. Notably, the EOs exhibited significant repellent activity against C. maculatus, with repulsion percentages ranging from 51.11 to 90.00% in Tanger and 67.78 to 93.33% in Meknes. Mortality rates varied from 0 to 100% depending on the treatment. However, the mean concentrations showed mortality rates ranging from 29.44 to 65.56% for the EOT and from 21.11 to 67.78% for the EOM, with LD50 values of 11.96 μL/L and 5.22 μL/L. Docking studies revealed that 1,8-cineole had the highest binding affinity for the active site of acetylcholinesterase, thus confirming its toxic activity against C. maculatus. The findings of this study highlight the ability of EOs extracted from L. nobilis in the Moroccan regions of Tanger and Meknes to act as effective insecticides and repellents against C. maculatus, thereby highlighting avenues for further exploration of pest management and agricultural practices. Full article

A novel single-step method has been developed for the synthesis of 1-(1-isocyanoethyl)adamantane from 1-(1-adamantylethyl)amine, chloroform, and t-BuOK, in a dichloromethane/tert-butanol (1:1) medium, yielding 92%, which is 27% higher compared to the known method, without the use of highly toxic compounds. The product was characterized using ¹H and ¹³C NMR spectroscopy, GC-MS, and elemental analysis. Full article

1,3-Alternate calix[4]arenes were prepared, having bulky adamantyl groups in the p-positions of all four aromatic units of the macrocycles and pairs of propargyl or 2-azidoethyl groups alternating with n-propyl groups at the phenol oxygen atoms. The step-wise syntheses were carried out through a selective distal alkylation of the parent p-adamantylcalix[4]arene with propargyl bromide or 1,2-dibromoethane, resulting in calix[4]arenes bearing pairs of propargyl or 2-bromoethyl groups at their narrow rims. The bromine atoms were replaced by azide groups, and then both calix[4]arene diethers were exhaustively alkylated at the remaining OH-groups with 1-iodopropane under stereoselective conditions to fix the macrocycles in an 1,3-alternate shape. The structures of the prepared p-adamantylcalix[4]arenes were confirmed by NMR and HRMS data, and, for the 1,3-alternate dipropargyl ether, the X-ray diffraction data were also collected. Preliminary data on the reactivity of the prepared calixarenes under the CuAAC conditions suggested a strong steric hampering created by the adamantane units nearby the reacting alkyne or azide groups that affected the outcome of the two-fold cycloaddition involving the calixarene bis(azides) or bis(alkynes) as complementary partners. Full article