Search Results (76)

Two fluorescent ureido-dihomooxacalix[4]arene derivatives containing naphthyl residues at the lower rim (1 and 2) were studied for the detection of nitroaromatic compounds (NACs) in solution and in vapour phases. Their affinity in solution was determined by UV-Vis absorption, fluorescence and NMR spectroscopy. For NAC vapour sensing, calixarenes were dispersed in a polytetrafluoroethylene (PTFE) matrix. Four new solvated crystals of dihomooxacalix[4]arene 2 were obtained and the solvent’s influence on its structural characteristics was investigated. The solvent-dependent structural variations observed in the crystal structures highlight the intrinsic flexibility of the calixarene framework. Such conformational adaptability, evident in the disruption and reorganization of hydrogen bonding and π–π interactions, is directly relevant to nitroaromatic sensing, where a rapid and reversible host response is crucial for effective detection. Theoretical calculations were also performed to provide further insights on the binding process. The corrected Stern–Volmer constants (K_SV) obtained showed that both receptors present selectivity for TNP and follow the same quenching order (TNP > NT > NB > DNT > TNT > DNB). Factors other than electron density distribution should dominate the quenching extent and therefore the values of the SV constants, which will be greatly overestimated if no correction to the inner filter effect is applied. Detection of NB and NT and vapours by both calixarenes produced a complete, very fast (2 to 5 s), and reversible quenching, indicating the potential use of this porous PTFE–calixarene matrix for the sensing of volatile NACs. Full article

This study explores the self-healing properties of polyurethane nanocomposites enhanced by multiple hydrogen bonds from ureido-pyrimidinone and the incorporation of 1–3 wt.% graphene nanoparticles, based on polyol α,ω-dihydroxy[oligo(butylene-ethylene adipate)]diol, which, according to our knowledge, has not been previously used in such systems. These new materials were synthesized via a two-step process and characterized by their thermal, mechanical, chemical, and self-healing properties. The mechanical analysis revealed that all nanocomposites exhibited high self-healing efficiencies (88–91%). The PU containing 2% graphene stands out as it exhibits the highest initial mechanical strength of ~5 MPa compared to approximately 2MP for a pristine PU while maintaining excellent self-healing efficiency (88%). A cut on the PU nanocomposite with 2% graphene can be completely healed after being heated at 80 °C for 1 h, which shows that it has a fast recovery time. Moreover, 3D printing was also successfully used to assess their processability and its effect on self-healing behavior. Three-dimensional printing did not negatively affect the material regeneration properties; thus, the material can be used in a variety of applications as expected in terms of dimensions and geometry. Full article

Receptors capable of binding both positive and negative ions are an important domain of supramolecular chemistry with valuable application potential. A Complete thermodynamic description of the equilibria related to ion pair recognition is beneficial in developing the optimized receptor systems, although it represents a difficult task that is rarely resolved due to various coupled processes. Here, we present a comprehensive study of ion pair (NaCl, NaHSO₄, and NaH₂PO₄) binding by a ureido–amide calix[4]arene host in acetonitrile using a series of experimental techniques and molecular dynamics simulations. We devoted particular attention to characterizing the side processes (ion association and salt precipitation) and included them in the models describing ion pair complex formation. For this purpose, a multimethod approach (potentiometry, conductometry, ITC, flame AES) was employed, generating reliable data which provided insight into the thermodynamic effect of each included equilibrium. Positive cooperativity was observed in the context of NaCl and NaHSO₄ binding by the studied calixarene. Computational results related to the NaCl complex in acetonitrile revealed that favorable Coulombic interactions, changes in affinity for solvent molecule inclusion, and intramolecular hydrogen bonding contributed to cation-induced cooperativity. Full article

The primary challenges in the tissue engineering of small-diameter artificial blood vessels include inadequate mechanical properties and insufficient anticoagulation capabilities. To address these challenges, urea-pyrimidone (Upy)-based polyurethane elastomers (PIIU-B) were synthesized by incorporating quadruple hydrogen bonding within the polymer backbone. The synthesis process employed poly(L-lactide-ε-caprolactone) (PLCL) as the soft segment, while di-(isophorone diisocyanate)-Ureido pyrimidinone (IUI) and isophorone diisocyanate (IPDI) were utilized as the hard segment. The resulting PIIU-B small-diameter artificial blood vessel with a diameter of 4 mm was fabricated using the electrospinning technique, achieving an optimized IUI/IPDI composition ratio of 1:1. Enhanced by multiple hydrogen bonds, the vessels exhibited a robust elastic modulus of 12.45 MPa, an extracellular matrix (ECM)-mimetic nanofiber morphology, and a high porosity of 41.31%. Subsequently, the PIIU-B vessel underwent dual-functionalization with low-molecular-weight heparin and gelatin via ultraviolet (UV) crosslinking (designated as PIIU-B@LHep/Gel), which conferred superior biocompatibility and exceptional anticoagulation properties. The study revealed improved anti-platelet adhesion characteristics as well as a prolonged activated partial thromboplastin time (APTT) of 157.2 s and thrombin time (TT) of 64.2 s in vitro. Following a seven-day subcutaneous implantation, the PIIU-B@LHep/Gel vessel exhibited excellent biocompatibility, evidenced by complete integration with the surrounding peri-implant tissue, significant cell infiltration, and collagen formation in vivo. Consequently, polyurethane-based artificial blood vessels, reinforced by multiple hydrogen bonds and dual-functionalized with heparin and gelatin, present as promising candidates for vascular tissue engineering. Full article

Background: The maximum standardised uptake value (SUV_max) can potentially be affected by the uptake period during PSMA PET imaging. The optimal image acquisition period for 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (¹⁸F-DCFPyL)PSMA PET/CT is yet to be established. This study aims to evaluate the effect of the uptake period on the SUV_max in diagnosing localised, clinically significant prostate cancer using ¹⁸F-DCFPyL-PSMA PET/CT. Methods: Sixty biopsy-naive men with one or more PI-RADS 4 or 5 lesions of at least 10 mm on multiparametric MRI (mpMRI) were enrolled to undergo ¹⁸F-DCFPyL-PSMA PET/CT. SUV_max was prospectively measured following an uptake period of 60, 90 and 120 min post injection of ¹⁸F-DCFPyL-PSMA radiotracer. Concordance with biopsy results or final histopathology was recorded. Results: Mean absolute differences in SUV_max at 60 vs. 90, 60 vs. 120, and 90 vs. 120 min uptake periods were 3.23 (SD 4.76), 4.53 (SD 7.33), and 3.24 (SD 4.56), respectively. This represents a statistically significant systematic increase in SUV_max (p-value < 0.001) with increasing uptake period. The interval between the uptake period of 60 vs. 120 min represented the largest SUV_max change of 29.98%. Conclusions: The SUV_max is a dynamic variable significantly affected by uptake period. Our study supports image acquisition at 120 min following injection of ¹⁸F-DCFPyL radiotracer. Further studies are needed to determine if this acquisition period can be applied to other Fluorine-18 based PSMA radiotracers. Full article

In the present study, synthesis, conformational behavior, host–guest complex formation, and electrochemical properties of novel 6-substituted-2-ureido-4-ferrocenylpyrimidines were explored. A comprehensive NMR spectroscopic investigation was carried out to confirm the structure and conformational equilibrium of the ureidopyrimidines through studying the temperature- and concentration dependence of NMR spectra. Low-temperature NMR measurements were used to clarify structural changes inflicted by a 2,6-diaminopyridine guest. Association constant (K_assoc) values of host–guest complexes were calculated based on low-temperature titrations. It was shown that the introduction of a pyridin-2-yl substituent in the pyrimidine ring in host 10 induced a considerable change not only in the conformational equilibrium of the host itself but also in that of the host–guest complex. Geometries and relative stabilities of the conformers of host 10 as well as its host–guest complexes were determined by quantum chemical calculations. Electrochemical behavior of ureidopyrimidine hosts and host–guest complexes was investigated by cyclic voltammetry (CV) and linear sweep voltammetry (LSV) measurements. Two ureidopyrimidine derivatives were immobilized on the surface of spectral graphite electrodes, and their electrochemical response on the addition of 2,6-diaminopyridine was compared. These results also supported the importance of the pyridin-2-yl substituent in the efficient sensing of the guest. Full article

This publication reports a facile and convenient preparation of tri-O-acetyl-glucopyranoses, derived from the corresponding 2-deoxyaminosugar, where the vicinal anomeric and C2 positions are decorated by azido and (thio)ureido groups, respectively. This double functionalization leads to an inherently chiral core incorporating the versatile azido and (thio)ureido linkages prone to further manipulation. The latter also provides a structural element for hydrogen-bonded donor-acceptor (HB-DA) sites, which are of immense value in organocatalytic pursuits. A computation-aided conformational analysis unveils the landscape of available conformers and their relative stability. N-aryl (thio)ureas bearing substituents at ortho positions exist as mixtures of M- and P-atropisomeric conformers. Full article

The Prostate cancer (PC) is a major problem all over worldwide and this is the second highest cancer-related mortality rate after lung cancer all over worldwide. At least 299,010 likely cases in men were reported in the US in 2024 and about 35,250 deaths are reported. The overexpression of prostate-specific membrane antigen (PSMA) is a key factor in the progression of prostate cancer and contributes to metastasis in lymph nodes, soft tissues and bones metastasis. The numerous studies have reported that, Glu-ureido-based molecules exhibit high binding affinity for PSMA. The earliest imaging agents developed from this structure were labeled with radioactive halogen isotopes and demonstrated nanomolar binding affinity, leading to exceptional imaging properties. Hence the Glu-ureido chemical moiety is a very important template as inhibitor of PSMA. In this study to explore the chemical structural and electronic features of Glu-Ureido structure with the aid of quantum chemistry computer simulations. In this study, first optimized the structure of this chemical structure using the B3LYP 6311-G (++, d, p) basis set. In this study investigated the maximal quantity of electronic charge transfer (N_max), chemical hardness (η), electrostatic potential, chemical potential (µ) and electrophilicity (ω). By the using Natural Bond Orbital (NBO) analysis, the examination shows that the molecule’s chemically active regions π-electron-electron delocalization within the molecule that contribute to its stability. Full article

Cancer cell mitochondria are functionally different from those in normal cells and could be targeted to develop novel anticancer agents. The aryl-ureido fatty acid CTU (16({[4-chloro-3-(trifluoromethyl)phenyl]-carbamoyl}amino)hexadecanoic acid) is the prototype of a new class of targeted agents that enhance the production of reactive oxygen species (ROS) that disrupt the outer mitochondrial membrane (OMM) and kill cancer cells. However, the mechanism by which CTU disrupts the inner mitochondrial membrane (IMM) and activates apoptosis is not clear. Here, we show that CTU-mediated ROS selectively dysregulated the OMA1/OPA1 fusion regulatory system located in the IMM. The essential role of ROS was confirmed in experiments with the lipid peroxyl scavenger α-tocopherol, which prevented the dysregulation of OMA1/OPA1 and CTU-mediated MDA-MB-231 cell killing. The disruption of OMA1/OPA1 and IMM fusion by CTU-mediated ROS accounted for the release of cytochrome c from the mitochondria and the activation of apoptosis. Taken together, these findings demonstrate that CTU depolarises the mitochondrial membrane, activates ROS production, and disrupts both the IMM and OMM, which releases cytochrome c and activates apoptosis. Mitochondrial-targeting agents like CTU offer a novel approach to the development of new therapeutics with anticancer activity. Full article

(1) Objective: The aim of this study was to observe the lipid-lowering effects of blood flow restriction training (BFR) combined with moderate-intensity continuous training (MICT) in obese college students by observing lipid-lowering hormones and untargeted metabolomics. (2) Methods: In this study, 14 obese college students were convened into three groups—MICT, MICT+BFR, and high-intensity interval training (HIIT)—for a crossover experiment. Blood was drawn before and after exercise for the analysis of lipolytic agents and untargeted metabolomics. The study used a paired t-test and ANOVA for statistical analyses. (3) Results: The lipolytic agent results showed that MICT+BFR was superior to the other two groups in terms of two agents (p = 0.000 and p = 0.003), namely, GH and IL-6 (difference between before and after testing: 10,986.51 ± 5601.84 and 2.42 ± 2.49, respectively), and HIIT was superior to the other two groups in terms of one agent (p = 0.000), i.e., EPI (22.81 ± 16.12). No advantage was observed for MICT. The metabolomics results showed that, compared to MICT, MICT+BFR was associated with the upregulated expression of xanthine, succinate, lactate, N-lactoylphenylalanine, citrate, ureido acid, and myristic acid after exercise, with the possibility of the involvement of the citric acid cycle, alanine, aspartic acid, glutamate metabolism, butyric acid metabolism, and the histidylate metabolism pathway. (4) Conclusions: The superior lipid-lowering effect of MICT+BFR over MICT in a group of obese college students may be due to the stronger activation of GH and IL-6 agents, with the citric acid cycle and alanine, aspartate, and glutamate metabolic pathways being associated with this type of exercise. Full article

Background: Alzheimer’s disease is a serious and widespread neurodegenerative illness in the modern healthcare scenario. GSK-3β and BuChE are prominent enzymatic targets associated with Alzheimer’s disease. Co-targeting GSK3β and BChE in Alzheimer’s disease helps to modify disease progression and enhance cognitive function by addressing both tau pathology and cholinergic deficits. However, the treatment arsenal for Alzheimer’s disease is extremely inadequate, with present medications displaying dismal success in treating this never-ending ailment. To create novel dual inhibitors, we have used molecular docking and dynamics analysis. Our focus was on analogs formed from the fusion of tacrine and amantadine ureido, specifically tailored to target GSK-3β and BuChE. Methods: In the following study, molecular docking was executed by employing AutoDock Vina and molecular dynamics and ADMET predictions were performed using the Desmond and Qikprop modules of Schrödinger. Results: Our findings unveiled that compounds DKS1 and DKS4 exhibited extraordinary molecular interactions within the active domains of GSK-3β and BuChE, respectively. These compounds engaged in highly favorable interactions with critical amino acids, including Lys85, Val135, Asp133, and Asp200, and His438, Ser198, and Thr120, yielding encouraging docking energies of −9.6 and −12.3 kcal/mol. Additionally, through extensive molecular dynamics simulations spanning a 100 ns trajectory, we established the robust stability of ligands DKS1 and DKS4 within the active pockets of GSK-3β and AChE. Particularly noteworthy was DKS5, which exhibited an outstanding human oral absorption rate of 79.792%, transcending the absorption rates observed for other molecules in our study. Conclusion: In summary, our in silico findings have illuminated the potential of our meticulously designed molecules as groundbreaking agents in the fight against Alzheimer’s disease, capable of simultaneously inhibiting both GSK-3β and BuChE. Full article

Prostate cancer represents a significant public health challenge, with its management requiring precise diagnostic and prognostic tools. Prostate-specific membrane antigen (PSMA), a cell surface enzyme overexpressed in prostate cancer cells, has emerged as a pivotal biomarker. PSMA’s ability to increase the sensitivity of PET imaging has revolutionized its application in the clinical management of prostate cancer. The advancements in PET-PSMA imaging technologies and methodologies, including the development of PSMA-targeted radiotracers and optimized imaging protocols, led to diagnostic accuracy and clinical utility across different stages of prostate cancer. This highlights its superiority in staging and its comparative effectiveness against conventional imaging modalities. This paper analyzes the impact of PET-PSMA on prostate cancer management, discussing the existing challenges and suggesting future research directions. The integration of recent studies and reviews underscores the evolving understanding of PET-PSMA imaging, marking its significant but still expanding role in clinical practice. This comprehensive review serves as a crucial resource for clinicians and researchers involved in the multifaceted domains of prostate cancer diagnosis, treatment, and management. Full article

The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating the development of novel agents targeting distinct pathways. To discover potent new anti-HCC compounds, we leveraged scaffold hopping from Sorafenib and introduced morpholine/piperidine moieties to develop ureido-substituted 4-phenylthiazole analogs with optimized physicochemical properties and binding interactions. Notably, compound 27 exhibited potent cytotoxicity against HepG2 cells (IC₅₀ = 0.62 ± 0.34 μM), significantly exceeding Sorafenib (IC₅₀ = 1.62 ± 0.27 μM). Mechanistic investigations revealed that compound 27 potently inhibited HCC cell migration and colony formation, and it induced G2/M arrest and early-stage apoptosis. Kinase profiling revealed IGF1R as a key target, which compound 27 potently inhibited (76.84% at 10 μM). Molecular modeling substantiated compound 27’s strong binding to IGF1R via multiple hydrogen bonds. Computational predictions indicate favorable drug-like properties for compound 27. These findings provide a promising drug candidate for the treatment of HCC patients. Full article

Citrulline (C₆H₁₃N₃O₃) is an amino acid found in the body as a zwitterion. This means its carboxylic and amine groups can act as Lewis donors to chelate metal cations. In addition, citrulline possesses a terminal ureido group on its aliphatic chain, which also appears to coordinate. Here, two new mixed complexes of citrulline were made with 1,10-phenanthroline and 2,2′-bipyridine. These compounds, once dissolved in water, gave aquo-complexes that were subject to DFT studies and in vitro toxicity studies on cancer cell lines (HeLa, MDA-MB-231, HCT 15, and MCF7) showed promising results. Docking studies with DNA were also conducted, indicating potential anticancer properties. Full article