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Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as compared to the normal vegetation in other climatic regions. Given the consistent increases in desertification around the world, which are associated with increasing salinity, high temperature, and water scarcity, the survival of halophytes due to their secondary metabolic contents has prioritized these plant species, which have now become increasingly important for environmental protection, land reclamation, and food and animal-feed security, with their primary utility in traditional societies as sources of drugs. On the medicinal herbs front, because the fight against cancer is still ongoing, there is an urgent need for development of more efficient, safe, and novel chemotherapeutic agents, than those currently available. The current review describes these plants and their secondary-metabolite-based chemical products as promising candidates for developing newer cancer therapeutics. It further discusses the prophylactic roles of these plants, and their constituents in prevention and management of cancers, through an exploration of their phytochemical and pharmacological properties, with a view on immunomodulation. The important roles of various phenolics and structurally diverse flavonoids as major constituents of the halophytes in suppressing oxidative stress, immunomodulation, and anti-cancer effects are the subject matter of this review and these aspects are outlined in details. [ABSTRACT FROM AUTHOR]

Three new uranyl complexes [(UO2)(OAc)2(CMZ)], [(UO2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)] were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, powder XRD analysis, and molar conductivity. The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands. [ABSTRACT FROM AUTHOR]

Thiamphenicol (TM) is an antimicrobial drug and a methyl-sulfonyl analogue of chloramphenicol. New metal complexes of TM with Zn(II), Cu(II), Ni(II), Co(II) and Fe(II) were synthesized and characterized using elemental analyses, infrared (IR) and proton nuclear magnetic resonance spectroscopy (1H-NMR), magnetic susceptibility, electron paramagnetic resonance (EPR) spectroscopy, and thermogravimetric analysis (TGA). The IR spectra revealed coordination of the deprotonated ligand to the metal through one oxygen and the nitrogen atom of the amide group. Moreover, EPR analysis of the Cu(II) solid sample indicated a distorted tetrahedral structure with a negligible exchange interaction between the Cu(II) ions. The UV-vis spectral results from the Co(II) and Fe(II) complexes showed a distorted tetrahedral geometric arrangement for both compounds. The DFT calculation approach was used to study the nature of the interaction between the metal ions and the ligand where the molecular stability and bond strengths were evaluated by Natural Bond Orbital (NBO) and quantum parameters. The biological activity of the metal complexes was investigated by several different bioassays. The DNA binding constant Kb showed an intercalation binding mode for both the free drug and the metal compounds. An in vitro protein (HSA) binding study showed binding with TM–Zn Kb = 9.87 × 105 M−1. The cytotoxic activity of each divalent complex was tested against two cell lines: (1) a human colon carcinoma (HCT-116) cell line and (2) a human breast carcinoma (MCF-7) tumor cell line and demonstrated anti-cancer cell activities. Molecular docking was utilized to explain the biological inhibition of the Cu(II) and Zn(II) complexes. [ABSTRACT FROM AUTHOR]

6‐mercaptopurine (6‐MP) is used for treating various cancers and autoimmune disorders. A few examples of transition metal complexes of 6‐MP have been shown to enhance its anticancer activity, but many remain untested. We isolated five highly stable and colored metal complexes of 6‐MP and confirmed their structures by elemental analysis, spectral, and thermal techniques. Infrared (IR) spectra revealed that 6‐MP is a bidentate ligand that interacts through sulfur and pyrimidine nitrogen in a 1:2 (M:L) molar ratio. The magnetic susceptibility and electron paramagnetic resonance (EPR) spectra for the Cu(II) complex revealed an octahedral arrangement around the metal ion with strong covalent bonding. The fully optimized geometries of the metal structures obtained using density function theory (DFT)/B3LYP calculations were used to verify the structural and biological features. DNA titration revealed that the octahedral Cu(II) complex has a critical binding constant value of Kb = 8 × 105. Docking studies using three different cancer protein receptors were used to predict the biological applications of the synthesized drug‐metal complexes. Finally, cytotoxicity assays against a myeloma cancer cell line (MM) and a colon cancer cell line (Caco‐2) revealed favorable anticancer activity for the copper complex, exceeding that of the gold‐standard chemotherapeutic cisplatin. [ABSTRACT FROM AUTHOR]

Iridium-catalyzed aromatic borylation provides quick onestep access to 2,6-bis(trifluoromethyl)pyridine-4-boronic acid pinacol ester. Suzuki couplings of this highly electron-deficient pyridine-4-boronic ester with various (hetero)aryl bromides was successfully carried out and the coupled products were obtained in 46–95% isolated yields. Double and triple Suzuki couplings, with dibromo- and tribromoarenes, respectively, were also achieved. Thus demonstrating that this pyridine- 4-boronic ester can be a useful source for the installation of one of the strongest electron-withdrawing aromatic group in organic compounds. [ABSTRACT FROM AUTHOR]

Iridium-catalyzed aromatic borylation provides quick onestep access to 2,6-bis(trifluoromethyl)pyridine-4-boronic acid pinacol ester. Suzuki couplings of this highly electron-deficient pyridine-4-boronic ester with various (hetero)aryl bromides was successfully carried out and the coupled products were obtained in 46-95% isolated yields. Double and triple Suzuki couplings, with dibromo- and tribromoarenes, respectively, were also achieved. Thus demonstrating that this pyridine-4-boronic ester can be a useful source for the installation of one of the strongest electron-withdrawing aromatic group in organic compounds. [ABSTRACT FROM AUTHOR]

In this work, the biological potency of nitazoxanide (NTZ) was enhanced through coordination with transition metal ions Cu(II), Ni(II), and Zn(II). Initially, complexes with a ligand-metal stoichiometry of 2:1 were successfully synthesized and characterized by spectroscopic techniques and thermogravimetric methods. Measurement of the infrared spectrum revealed the bidentate nature of the ligand and excluded the possibility of the metal ion—amide group interaction. Nuclear magnetic resonance spectra showed a reduction in the NH- intensity signal and integration, indicating the possibility of enolization and the formation of keto-enol tautomers. To interpret these results, density functional theory was utilized under B3LYP/6-311G** for the free ligand and B3LYP/LANL2DZ for the metal complexes. We used UV-Vis and fluorescence spectroscopy to understand the biological properties of the complexes. This showed stronger interactions of NTZ-Cu(II) and NTZ-Ni(II) with DNA molecules than the NTZ-Zn(II) compound, with a binding constant (Kb) for the copper complex of 7.00 × 105 M−1. Both Cu(II)- and Ni(II)-NTZ had functional binding to the SARS-CoV-2 (6LU7) protease. Moreover, all metal complexes showed better antioxidation properties than the free ligand, with NTZ-Ni(II) having the best IC50 value of 53.45 μg/mL. NTZ-Ni(II) was an effective antibacterial, with a mean inhibitory concentration of 6 μM, which is close to that of ampicillin (a reference drug). The metal complexes had moderated anticancer potencies, with NTZ-Cu(II) having IC50 values of 24.5 and 21.5 against human breast cancer cells (MCF-7) and cancerous cervical tumor cells (HeLa), respectively. All obtained complexes exhibited high selectivity. Finally, the metal ions showed a practical role in improving the biological effectiveness of NTZ molecules. [ABSTRACT FROM AUTHOR]

Benzimidazoles are classified as a category of heterocyclic compounds. Molecules having benzimidazole motifs show promising utility in organic and scientific studies. A series of mono-substituted benzimidazoles were synthesized by ZnO-NPs via cyclocondensation between substituted aromatic aldehydes and o-phenylene diamine. The synthesized compounds were characterized and compared with the traditional methods. The nano-catalyzed method displayed a higher yield, shorter time and recyclable catalyst. The DFT study and antioxidant activity were investigated for benzo[d]imidazole derivatives. Compound 2a exhibited the highest antioxidant activity among the tested compounds. We focused on the catalytic activity of ZnO in the synthesis of heterocyclic structures with the goal of stimulating further progress in this field. The superiorities of this procedure are high yield of product, low amounts of catalyst and short reaction time. [ABSTRACT FROM AUTHOR]

The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition. [ABSTRACT FROM AUTHOR]

Metabolomics is a dynamic and emerging research field, similar to proteomics, transcriptomics and genomics in affording global understanding of biological systems. It is particularly useful in functional genomic studies in which metabolism is thought to be perturbed. Metabolomics provides a snapshot of the metabolic dynamics that reflect the response of living systems to both pathophysiological stimuli and/or genetic modification. Because this approach makes possible the examination of interactions between an organism and its diet or environment, it is particularly useful for identifying biomarkers of disease processes that involve the environment. For example, the interaction of a high fat diet with cardiovascular disease can be studied via such a metabolomics approach by modeling the interaction between genes and diet. The high reproducibility of NMR-based techniques gives this method a number of advantages over other analytical techniques in large-scale and long-term metabolomic studies, such as epidemiological studies. This approach has been used to study a wide range of diseases, through the examination of biofluids, including blood plasma/serum, urine, blister fluid, saliva and semen, as well as tissue extracts and intact tissue biopsies. However, complicating the use of NMR spectroscopy in biomarker discovery is the fact that numerous variables can effect metabolic composition including, fasting, stress, drug administration, diet, gender, age, physical activity, life style and the subject's health condition. To minimize the influence of these variations in the datasets, all experimental conditions including sample collection, storage, preparation as well as NMR spectroscopic parameters and data analysis should be optimized carefully and conducted in an identical manner as described by the local standard operating protocol . This review highlights the potential applications of NMR-based metabolomics studies and gives some recommendations to improve sample collection, sample preparation and data analysis in using this approach. [ABSTRACT FROM AUTHOR]

Copper is an essential nutrient for the normal development of the brain and nervous system, although the hallmark of several neurological diseases is a change in copper concentrations in the brain and central nervous system. Prion protein (PrP) is a copper-binding, cell-surface glycoprotein that exists in two alternatively folded conformations: a normal isoform (PrPC) and a disease-associated isoform (PrPSc). Prion diseases are a group of lethal neurodegenerative disorders that develop as a result of conformational conversion of PrPC into PrPSc. The pathogenic mechanism that triggers this conformational transformation with the subsequent development of prion diseases remains unclear. It has, however, been shown repeatedly that copper plays a significant functional role in the conformational conversion of prion proteins. In this review, we focus on current research that seeks to clarify the conformational changes associated with prion diseases and the role of copper in this mechanism, with emphasis on the latest applications of NMR and EPR spectroscopy to probe the interactions of copper with prion proteins. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The reaction of 1-naphthylamine with one equivalent of chlorodiphenylphosphine in the presence of triethylamine gave the (1-NHC10H7)PPh2 (1) ligand. Refluxing of 1 with elemental sulfur or grey selenium in toluene (1:1 molar ratio) afforded (1-NHC10H7)P(S)Ph2 (2) and (1-NHC10H7)P(Se)Ph2 (3), respectively. Moreover, the byproduct {Ph2P(S)}2O (4) was isolated from the reaction of 1 with elemental sulfur. Compounds 1–3 were identified and characterized by multinuclear (1H, 13C, 31P, 77Se) NMR spectroscopy, mass spectrometry, and elemental analysis. Crystal structure determinations of 3 and 4 were carried out. [ABSTRACT FROM AUTHOR]

We report the first solid-state 27Al NMR study of three aluminum phthalocyanine dyes: aluminum phthalocyanine chloride, AlPcCl (1); aluminum-1,8,15,22-tetrakis(phenylthio)-29H,31H-phthalocyanine chloride, AlPc(SPh)4Cl (2); and aluminum-2,3-naphthalocyanine chloride, AlNcCl (3). Each of these compounds contains Al3+ ions coordinating to four nitrogen atoms and a chlorine atom. Solid-state 27Al NMR spectra, including multiple-quantum magic-angle spinning (MQMAS) spectra and quadrupolar Carr–Purcell–Meiboom–Gill (QCPMG) spectra of stationary powdered samples have been acquired at multiple high magnetic field strengths (11.7, 14.1, and 21.1 T) to determine their composition and number of aluminum sites, which were analyzed to extract detailed information on the aluminum electric field gradient (EFG) and nuclear magnetic shielding tensors. The quadrupolar parameters for each 27Al site were determined from spectral simulations, with quadrupolar coupling constants (CQ) ranging from 5.40 to 10.0 MHz and asymmetry parameters (η) ranging from 0.10 to 0.50, and compared well with the results of quantum chemical calculations of these tensors. We also report the largest 27Al chemical shielding anisotropy (CSA), with a span of 120 ± 10 ppm, observed directly in a solid material. The combination of MQMAS and computational predictions are used to interpret the presence of multiple aluminum sites in two of the three samples. [ABSTRACT FROM AUTHOR]

Abstract: Blood serum is commonly used for clinical diagnostics because its protein composition bears a wealth of information about the health of an organism. More recently the analysis of the small molecule composition, the metabolome, has received increased attention because the metabolite composition is influenced by many diseases, by the administration of drugs and toxins, and by the diet and life style of an individual. When nuclear magnetic resonance spectroscopy is used as an analytical tool it is often preferable to remove catalytically active proteins, in particular for longer measurements, because metabolite concentrations are otherwise in constant flux. Here we have compared different protocols for the separation of proteins and metabolites, including precipitation methods and ultrafiltration. Whereas most extraction methods involving protein precipitation deplete some metabolites, ultrafiltration is superior in retaining metabolite concentrations and offers excellent reproducibility. We also describe a new method to recover the hydrophobic fraction for ultrafiltration with good reproducibility. [Copyright &y& Elsevier]

• Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder and model for misfolding protein diseases. • AATD polymorphism leads to essential metal ions (iron, copper and zinc) dyshomeostasis, but there are no biochemical models of Alpha-1 antitrypsin (AAT) metal coordination and possible implications. • Metal dyshomeostasis as well as metal/peptide and metal/protein interactions are correlated with misfolding protein pathologies as Type 2 Diabetes Mellitus (T2DM) and neurodegeneration (dementia, Alzheimer's disease (AD), Parkinson's Disease (PD), prion diseases). • Conformational diseases are not distinct pathologies, but the same pathological state that is correlated with AAT polymorphism, and develop in different tissues at different stages of life. Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemy-aggregating proteins may reside in these underdiagnosed AATD patients for many years before a pathology for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2 diabetes mellitus (T2DM), Alzheimer's and Parkinson's diseases, respectively. [ABSTRACT FROM AUTHOR]

In recent years, self‐assembled monolayers (SAMs) have been proven to work efficiently as hole‐selective materials in both organic solar cells (OSCs) and perovskite solar cells. Although competitive performances are reported with these materials, a mechanistic understanding on device stability remains elusive. This study reveals that while various SAM molecules can increase the indium tin oxide (ITO) work function versus vacuum, they may not consistently result in monolayers that ensure simultaneous improvement in performance and operational stability of devices. Energetically, achieving alignment between the work function of the SAM‐modified electrode and the ionization energy (IE) of the donor is shown to be crucial for a low hole injection barrier, irrespective of the SAM's IE. Light‐induced degradation in the widely used SAM, (2‐(9H‐carbazol‐9‐yl)ethyl) phosphonic acid (2PACz), is identified through diverse aging tests and comprehensive chemical and electronic characterizations. This degradation involves SAM molecule decomposition and chemical reactions with the photoactive layer, contributing further to device degradation. Addressing these challenges, sputtered nickel oxide/SAM bilayers are proposed as hole‐selective contact with tailored interface energetics for both efficient and photostable OSCs, offering a promising alternative to commonly used hygroscopic PEDOT:PSS in OSCs. [ABSTRACT FROM AUTHOR]

Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with β-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation. [ABSTRACT FROM AUTHOR]

Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both non-toxic and non-amyloidogenic. Their primary sequences exhibit only slight variations in a few amino acid residues, primarily concentrated in the central region, spanning residues 20 to 29. This inspired us to study this fragment and investigate the impact on the aggregation properties of substituting residues within the central region of amylin and its analogs. Six fragments derived from amylin have undergone comprehensive testing against various metal ions by implementing a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Thioflavin T (ThT) assays, Atomic Force Microscopy (AFM), and cytotoxicity assays. These methodologies serve to provide a thorough understanding of how the substitutions and interactions with metal ions impact the aggregation behavior of amylin and its analogs. [ABSTRACT FROM AUTHOR]

Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a "gold standard" platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development. [ABSTRACT FROM AUTHOR]

To identify new candidate anticancer compounds, we here report the synthesis of benzimidazole derivatives: diethyl 2,2′-(2-oxo-1H-benzo[d]imidazole-1,3(2H)-diyl) diacetate and its arylideneacetohydrazide derivatives, using ultrasonic irradiation and conventional heating. The compounds were confirmed by Nuclear magnetic resonance (NMR) (JEOL, Tokyo, Japan) and Fourier transform infrared spectroscopy (FTIR) spectroscopy (Thermoscientific, Waltham, MA, USA). The molecular structure and electronic properties of the studied compounds were predicted for the acetohydrazide hydrazones. These compounds exist as a mixture of configurational and conformational isomerism as well as amido-amidic acid tautomerism. The NMR spectral data proved the predominance of syn-E amido isomers. In addition, density functional theory (DFT) predicted stability in the gas phase and showed that syn-E amido isomers are the most stable in the presence of an electron donating group, while the anti-isomer is the most stable in the presence of electron-attracting substituents. The anticancer activity of these synthetic compounds 6a, 6b and 6c towards both colon cancer (HCT-116) and cervical cancer (HeLa) cells was examined by MTT assay and DAPI staining. The MTT assay revealed a strong antiproliferative effect against the cancer cells at low concentrations, and interestingly, no significant inhibitory action against the non-cancerous cell line, HEK-293. The IC50 values for HCT-116 were 29.5 + 4.53 µM, 57.9 + 7.01 µM and 40.6 + 5.42 µM for 6a, 6b, and 6c, respectively. The IC50 values for HeLa cells were 57.1 + 6.7 µM, 65.6 + 6.63 µM and 33.8 + 3.54 µM for 6a, 6b, and 6c, respectively. DAPI staining revealed that these synthesized benzimidazole derivatives caused apoptotic cell death in both the colon and cervical cancer cells. Thus, these synthetic compounds demonstrate encouraging anticancer activity as well as being safe for normal human cells, making them attractive candidates as anticancer agents. [ABSTRACT FROM AUTHOR]

Rechargeable Mg batteries promise low‐cost, safe, and high‐energy alternatives to Li‐ion batteries. However, the high polarization strength of Mg2+ leads to its strong interaction with electrode materials and electrolyte molecules, resulting in sluggish Mg2+ dissociation and diffusion as well as insufficient power density and cycling stability. Here an aqueous Mg2+‐based dual‐ion battery is reported to bypass the penalties of slow dissociation and solid‐state diffusion. This battery chemistry utilizes fast redox reactions on the polymer electrodes, i.e., anion (de)doping on the polyaniline (PANI) cathode and (de)enolization upon incorporating Mg2+ on the polyimide anode. The kinetically favored and stable electrodes depend on designing a saturated aqueous electrolyte of 4.5 m Mg(NO3)2. The concentrated electrolyte suppresses the irreversible deprotonation reaction of the PANI cathode to enable excellent stability (a lifespan of over 10 000 cycles) and rate performance (33% capacity retention at 500 C) and avoids the anodic parasitic reaction of nitrate reduction to deliver the stable polyimide anode (86.2% capacity retention after 6000 cycles). The resultant full Mg2+‐based dual‐ion battery shows a high specific power of 10 826 W kg−1, competitive with electrochemical supercapacitors. The electrolyte and electrode chemistries elucidated in this study provide an alternative approach to developing better‐performing Mg‐based batteries. [ABSTRACT FROM AUTHOR]

Crosslinked polythiosemicarbazide (PTSC) membranes with a positively charged surface are fabricated via a reaction with (3‐glycidyloxypropyl)trimethoxysilane. The integrally asymmetric ultrafiltration membranes discussed here can be easily prepared by water‐induced phase separation using a PTSC solution in dimethylsulfoxide (DMSO). The crosslinked PTSC membranes are stable in DMSO, N,N‐dimethylformamide, and tetrahydrofuran and they reject molecules of molecular weights (MW) above 1300 g mol−1. The influence of the crosslinking agent on the surface charge, membrane solvent resistance, and membrane performance is discussed. The crosslinked asymmetric PTSC membranes totally reject Direct Red dye (MW 1373 g mol−1), while the pristine PTSC membrane does not show any rejection for this dye. This finding suggests that an inorganic‐type‐network is formed during the crosslinking reaction, which tunes the pore size of the prepared membranes. An integral asymmetric membrane prepared from polythiosemicarbazide is crosslinked with a functionalized trimethoxysilane. These membranes with a molecular weight cut‐off of about 1300 exhibit high stability in common organic solvents such as tetrahydrofuran, N,N‐dimethylformamide, and dimethylsulfoxide. The high stability is attributed to the formation of an organic–inorganic network. [ABSTRACT FROM AUTHOR]

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy. [ABSTRACT FROM AUTHOR]

Introduction: Nuclear Magnetic Resonance (NMR) spectroscopy stands as a preeminent analytical tool in the field of metabolomics. Nevertheless, when it comes to identifying metabolites present in scant amounts within various types of complex mixtures such as plants, honey, milk, and biological fluids and tissues, NMR-based metabolomics presents a formidable challenge. This predicament arises primarily from the fact that the signals emanating from metabolites existing in low concentrations tend to be overshadowed by the signals of highly concentrated metabolites within NMR spectra. Objectives: The aim of this study is to tackle the issue of intense sugar signals overshadowing the desired metabolite signals, an optimal pulse sequence with band-selective excitation has been proposed for the suppression of sugar's moiety signals (SSMS). This sequence serves the crucial purpose of suppressing unwanted signals, with a particular emphasis on mitigating the interference caused by sugar moieties' signals. Methods: We have implemented this comprehensive approach to various NMR techniques, including 1D 1H presaturation (presat), 2D J-resolved (RES), 2D 1H-1H Total Correlation Spectroscopy (TOCSY), and 2D 1H-13C Heteronuclear Single Quantum Coherence (HSQC) for the samples of dates-flesh, honey, a standard stock solution of glucose, and nine amino acids, and commercial fetal bovine serum (FBS). Results: The outcomes of this approach were significant. The suppression of the high-intensity sugar signals has considerably enhanced the visibility and sensitivity of the signals emanating from the desired metabolites. Conclusion: This, in turn, enables the identification of a greater number of metabolites. Additionally, it streamlines the experimental process, reducing the time required for the comparative quantification of metabolites in statistical studies in the field of metabolomics. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non‐nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti‐HIV drugs. Zidovudine, didanosine, and stavudine are FDA‐approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA‐approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV‐1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA‐approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART). [ABSTRACT FROM AUTHOR]

1H NMR spectra from urine can yield information-rich data sets that offer important insights into many biological and biochemical phenomena. However, the quality and utility of these insights can be profoundly affected by how the NMR spectra are processed and interpreted. For instance, if the NMR spectra are incorrectly referenced or inconsistently aligned, the identification of many compounds will be incorrect. If the NMR spectra are mis-phased or if the baseline correction is flawed, the estimated concentrations of many compounds will be systematically biased. Furthermore, because NMR permits the measurement of concentrations spanning up to five orders of magnitude, several problems can arise with data analysis. For instance, signals originating from the most abundant metabolites may prove to be the least biologically relevant while signals arising from the least abundant metabolites may prove to be the most important but hardest to accurately and precisely measure. As a result, a number of data processing techniques such as scaling, transformation and normalization are often required to address these issues. Therefore, proper processing of NMR data is a critical step to correctly extract useful information in any NMR-based metabolomic study. In this review we highlight the significance, advantages and disadvantages of different NMR spectral processing steps that are common to most NMR-based metabolomic studies of urine. These include: chemical shift referencing, phase and baseline correction, spectral alignment, spectral binning, scaling and normalization. We also provide a set of recommendations for best practices regarding spectral and data processing for NMR-based metabolomic studies of biofluids, with a particular focus on urine. [ABSTRACT FROM AUTHOR]

Methyl 4-hydroxybenzoate, commonly known as methyl paraben, is an anti-microbial agent used in cosmetics and personal-care products, and as a food preservative. In this study, the single crystal X-ray structure of methyl 4-hydroxybenzoate was determined at 120 K. The crystal structure comprises three methyl 4-hydroxybenzoate molecules condensed to a 3D framework via extensive intermolecular hydrogen bonding. Hirshfeld surface analysis was performed to determine the intermolecular interactions and the crystal packing. In addition, computational calculations of methyl 4-hydroxybenzoate were obtained using the Gaussian 09W program, and by quantum mechanical methods, Hartree Fock (HF) and Density Functional Theory (DFT) with the 6–311G(d,p) basis set. The experimental FT-IR spectrum strongly correlated with the computed vibrational spectra (R2 = 0.995). The energies of the frontier orbitals, HOMO and LUMO, were used to calculate the chemical quantum parameters. The lower band gap value (ΔE) indicates the molecular determinants underlying the known pharmaceutical activity of the molecule. [ABSTRACT FROM AUTHOR]

Tailoring fuel properties to maximize the efficiency of internal combustion engines is a way towards achieving cleaner combustion systems. In this work, the ignition properties along with the chemical composition (expressed as functional groups) of various light distillate (e.g., gasoline) cuts were analyzed to better understand the properties of full boiling range fuels. Various distillation cuts were obtained with a spinning band distillation system, which were then tested in an ignition quality tester (IQT) to obtain their global chemical reactivity (i.e., ignition delay time (IDT)). The distillates were further analyzed with 1H nuclear magnetic resonance (NMR) spectroscopy to identify and quantify various functional groups present in them. Various gasolines of research grade with specific target properties set forth by the Coordinating Research Council (CRC) that are known as FACE (fuels for advanced combustion engines) gasolines were distilled. When fuels with low aromatic content were distilled, the higher boiling point (BP) range (i.e., higher molecular weight) fractions exhibited lower IDT. However, distilled fractions of fuels with high aromatic content showed an initial decrease in IDT with increasing BP, followed by drastic increase in IDT primarily due to increasing aromatic groups. This study provides an understanding of the contribution of various volatile fractions to the IDTs of a multicomponent fuel, which is of relevance to fuel stratification utilized in gasoline compression ignition (GCI) engines to tailor heat release rates. [ABSTRACT FROM AUTHOR]

Herein, we report the synthesis of a new class of functional silver nanoclusters (AgNCs) capped with pillar[5]arene (P5)‐based host ligands. These NCs are readily prepared through direct synthesis or ligand exchange synthesis and are stable at room temperature for over 4 months. The pillar[5]arene‐stabilized NCs (Ag29(LA‐P5)12(TPP)2) endorse reversible host–guest interactions with neutral alkylamines and cationic quaternary ammonium guests. This results in the formation of spherical assemblies with unparalleled changes in their optical properties including an astonishing circa 2000‐fold luminescence enhancement. This is the highest luminescence enhancement ratio reported so far for such atomically precise NCs. Our synthetic protocol paves the way for the preparation of a new generation of metal nanoclusters protected by macrocyclic ligands with molecular recognition and selectivity toward specific guests. [ABSTRACT FROM AUTHOR]

Herein, we report the synthesis of a new class of functional silver nanoclusters (AgNCs) capped with pillar[5]arene (P5)‐based host ligands. These NCs are readily prepared through direct synthesis or ligand exchange synthesis and are stable at room temperature for over 4 months. The pillar[5]arene‐stabilized NCs (Ag29(LA‐P5)12(TPP)2) endorse reversible host–guest interactions with neutral alkylamines and cationic quaternary ammonium guests. This results in the formation of spherical assemblies with unparalleled changes in their optical properties including an astonishing circa 2000‐fold luminescence enhancement. This is the highest luminescence enhancement ratio reported so far for such atomically precise NCs. Our synthetic protocol paves the way for the preparation of a new generation of metal nanoclusters protected by macrocyclic ligands with molecular recognition and selectivity toward specific guests. [ABSTRACT FROM AUTHOR]

Three new quaternary compounds Na2BiSbQ4 (Q = S, Se, Te) have been synthesized by the direct combination reaction between Bi, Sb, Q and the corresponding Na2Q. All phases, sulfide, selenide and telluride, are isostructural and crystallize in the NaCl-type cubic space group Fm3̅m (no. 225) with lattice constants of a = 5.760(7), 5.964(9) and 6.331(5) Å, respectively. The unique feature of these structures is the existence of only one crystallographic metal site in the unit cell. These mixed position sites provide the desirable lattice complexity with a random distribution of the Na, Bi and Sb atoms. Consequently, extremely low thermal conductivities at room temperature have been observed for the studied phases. All three compounds are semiconductors and their Uv/Vis spectra exhibit redshifts toward narrower bandgap energies from sulfide to selenide to telluride. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Synthesis of [Ni(en) 3 ]GeS 2 (OH) 2 ·H 2 O by mild solvothermal route. • Structural investigation utilizing X-ray diffraction, 1H NMR and EPR spectroscopy. • Magnetization measurements revealing the paramagnetic character. • Optical spectroscopic studies determining the bandgap energy and the PL emission. Abstract A new tris(ethylenediamine)nickel(II) complex [Ni(en) 3 ]GeS 2 (OH) 2 ·H 2 O containing a zero-dimensional thiohydroxogermanate [GeS 2 (OH) 2 ]2− anion was synthesized using a solvothermal reaction. The compound crystallizes in monoclinic space group P 2 1 /n with cell parameters a = 8.676(3) Å, b = 13.574(4) Å, c = 13.976(4) Å and β = 92.67(2)°. The ethylenediamine (en) ligands are bidentate to the Ni2+ through the N atoms of the amine group resulting in a distorted octahedral environment around the transition metal. The solid-state 1H NMR shows four broad singlets attributed to the –CH 2 and –NH 2 protons of the (en) in addition to H 2 O and –OH protons. The EPR results indicate that the octahedrally coordinated Ni2+ cations are paramagnetic with two unpaired electrons. In agreement with the EPR results, the ZFC/FC magnetization measurements show a paramagnetic response. The title compound is a wide bandgap semiconductor (3.9 eV) and exhibits photoluminescence emission at 488 nm upon excitation (325 nm). [ABSTRACT FROM AUTHOR]

Abstract: Complexes made by hosts that completely surround their guests provide a means to stabilize reactive chemical intermediates, transfer biologically active cargo to a diseased cell, and construct molecular‐scale devices. By the virtue of inorganic host–guest self‐assembly, nucleation processes in the cavity of a {P8W48}‐archetype phosphotungstate has afforded a nanoscale 16‐AlIII‐32‐oxo cluster and its GaIII analogue that contain the largest number of AlIII/GaIII ions yet found in polyoxometalate (POM) chemistry. Interestingly, the rich Lewis acid AlIII centers within the Lewis base POM support shows an exceptional proton conductivity of 4.5×10−2 S cm−1 (85 °C, 70 % RH; RH: relative humidity), which is by far the highest conductivity reported among POM‐based single‐crystal proton conductors. [ABSTRACT FROM AUTHOR]

Abstract: Complexes made by hosts that completely surround their guests provide a means to stabilize reactive chemical intermediates, transfer biologically active cargo to a diseased cell, and construct molecular‐scale devices. By the virtue of inorganic host–guest self‐assembly, nucleation processes in the cavity of a {P8W48}‐archetype phosphotungstate has afforded a nanoscale 16‐AlIII‐32‐oxo cluster and its GaIII analogue that contain the largest number of AlIII/GaIII ions yet found in polyoxometalate (POM) chemistry. Interestingly, the rich Lewis acid AlIII centers within the Lewis base POM support shows an exceptional proton conductivity of 4.5×10−2 S cm−1 (85 °C, 70 % RH; RH: relative humidity), which is by far the highest conductivity reported among POM‐based single‐crystal proton conductors. [ABSTRACT FROM AUTHOR]

Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication. [ABSTRACT FROM AUTHOR]

The purpose of this study was to enhance the antimicrobial activity of bagasse paper by coating the paper with bismuth oxide (Bi2O3) and using it to accelerate the process of wound healing. Paper sheets were prepared from sugarcane waste (bagasse). First, the paper sheets were coated with different Bi2O3 concentrations to improve the antimicrobial activity of the paper. After that, the paper sheets were allowed to dry in an oven at 50 °C for 3 h. Then, in vitro antimicrobial activity was evaluated against different microbial species, including Gram-negative bacteria (i.e., Klebsiella pneumonia, Escherichia coli) and Gram-positive bacteria (i.e., Staphylococcus aureus, Streptococcus pyogenes). The obtained results showed that the paper coated with 25% and 100% Bi2O3 had activity against all models of bacteria; however, the paper coated with 100% Bi2O3 composite had the strongest inhibitory effect. Then, bagasse paper was coated with 100% Bi2O3 and different antibiotics, to investigate their wound-healing potency in a wounded rat model for 14 days. Moreover, the paper coated with 100% Bi2O3 inhibited the cellular migration in vitro. Conclusively, coating paper with Bi2O3 enhances the wound-healing potential when applied to wounds. This impact could be ascribed to Bi2O3's broad antibacterial activity, which reduced infection and accelerated the healing process. [ABSTRACT FROM AUTHOR]

• The seawater bacterial growth potential of eight diverse antiscalants is presented. • Phosphonate-based antiscalants promoted a broad range of seawater bacterial growth. • Phosphonate antiscalant without orthophosphates did not promote bacterial growth. • Biopolymers and polymers-based antiscalants promoted limited bacterial growth. • Antiscalants NMR fingerprinting contributes to an informed selection of antiscalants. 20 years since the first report on the biofouling potential of chemicals used for scale control, still, antiscalants with high bacterial growth potential are used in practice. Evaluating the bacterial growth potential of commercially available antiscalants is therefore essential for a rational selection of these chemicals. Previous antiscalant growth potential tests were conducted in drinking water or seawater inoculated with model bacterial species which do not represent natural bacterial communities. To reflect better on the conditions of desalination systems, we investigated the bacterial growth potential of eight different antiscalants in natural seawater and an autochthonous bacterial population as inoculum. The antiscalants differed strongly in their bacterial growth potential varying from ≤ 1 to 6 μg easily biodegradable C equivalents/mg antiscalant. The six phosphonate-based antiscalants investigated showed a broad range of growth potential, which depended on their chemical composition, whilst the biopolymer and the synthetic carboxylated polymers-based antiscalants showed limited or no significant bacterial growth. Moreover, nuclear magnetic resonance (NMR) scans enabled antiscalant fingerprinting, identifying components and contaminants, providing a rapid and sensitive characterization, and opening opportunities for rational selection of antiscalants for biofouling control. [Display omitted] [ABSTRACT FROM AUTHOR]

Carbonaceous materials are promising anodes for practical potassium‐ion batteries, but fail to meet the requirements for durability and high capacities at low potentials. Herein, we constructed a durable carbon anode for high‐energy‐density K‐ion full cells by a preferential pyrolysis strategy. Utilizing S and N volatilization from a π–π stacked supermolecule, the preferential pyrolysis process introduces low‐potential active sites of sp2 hybridized carbon and carbon vacancies, endowing a low‐potential "vacancy‐adsorption/intercalation" mechanism. The as‐prepared carbon anode exhibits a high capacity of 384.2 mAh g−1 (90 % capacity locates below 1 V vs. K/K+), which contributes to a high energy density of 163 Wh kg−1 of K‐ion full battery. Moreover, abundant vacancies of carbon alleviate volume variation, boosting the cycling stability over 14 000 cycles (8400 h). Our work provides a new synthesis approach for durable carbon anodes of K‐ion full cells with high energy densities. [ABSTRACT FROM AUTHOR]

Carbonaceous materials are promising anodes for practical potassium‐ion batteries, but fail to meet the requirements for durability and high capacities at low potentials. Herein, we constructed a durable carbon anode for high‐energy‐density K‐ion full cells by a preferential pyrolysis strategy. Utilizing S and N volatilization from a π–π stacked supermolecule, the preferential pyrolysis process introduces low‐potential active sites of sp2 hybridized carbon and carbon vacancies, endowing a low‐potential "vacancy‐adsorption/intercalation" mechanism. The as‐prepared carbon anode exhibits a high capacity of 384.2 mAh g−1 (90 % capacity locates below 1 V vs. K/K+), which contributes to a high energy density of 163 Wh kg−1 of K‐ion full battery. Moreover, abundant vacancies of carbon alleviate volume variation, boosting the cycling stability over 14 000 cycles (8400 h). Our work provides a new synthesis approach for durable carbon anodes of K‐ion full cells with high energy densities. [ABSTRACT FROM AUTHOR]

The date palm has been cultivated in dry and hot areas of the planet for much of human history. In the Kingdom of Saudi Arabia, dates are the main crop used as a source of food. Among several species of date fruits, the Ajwa AL-Madinah date is unique, growing only in Al-Madinah geographical region. The Ajwa date is used in traditional medicine due to its abundant active components and therapeutic properties. This study investigates the structural properties and the antioxidant effects of water-soluble polysaccharides extracted from Ajwa flesh and seed. The polysaccharides were isolated by two techniques including hot water and ultrasonic extraction. After isolation and partial purification, the physicochemical properties of four samples of polysaccharides extracted from flesh and seed were studied by several techniques including FTIR, solid-state NMR, elemental analysis, and mass spectrometry. Several radical scavenging experiments were combined to study the antioxidant activity of the polysaccharide compounds. FTIR and NMR results showed a structure typical of heterogeneous polysaccharides. Mass spectrometry revealed that the polysaccharide samples were composed mainly of mannose, glucose, galactose, xylose, arabinose, galacturonic acid, and fucose. In addition, the physicochemical properties and composition of polysaccharides extracted from flesh and seed were compared. The extracted polysaccharides showed antioxidant activity, with 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, Fe chelating ability, hydroxyl free radical scavenging ability, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. These results highlight their potential to be a useful nutritional element or supplemental medication. [ABSTRACT FROM AUTHOR]

Cancer is one of the major healthcare challenges across the globe. Several anticancer drugs are available on the market but they either lack specificity or have poor safety, severe side effects, and suffer from resistance. So, there is a dire need to develop safer and target-specific anticancer drugs. More than 85% of all physiologically active pharmaceuticals are heterocycles or contain at least one heteroatom. Nitrogen heterocycles constituting the most common heterocyclic framework. In this study, we have compiled the FDA approved heterocyclic drugs with nitrogen atoms and their pharmacological properties. Moreover, we have reported nitrogen containing heterocycles, including pyrimidine, quinolone, carbazole, pyridine, imidazole, benzimidazole, triazole, β-lactam, indole, pyrazole, quinazoline, quinoxaline, isatin, pyrrolo-benzodiazepines, and pyrido[2,3-d]pyrimidines, which are used in the treatment of different types of cancer, concurrently covering the biochemical mechanisms of action and cellular targets. [ABSTRACT FROM AUTHOR]

The aim of the present study is to develop Doxorubicin–Erlotinib nanoparticles (Dox–Erlo NPs) and folate-armored Dox–Erlo-NP conjugates for targeting glioma cancer. Glioma is one of the most common progressive cancerous growths originating from brain glial cells. However, the blood–brain barrier (BBB) is only semi-permeable and is highly selective as to which compounds are let through; designing compounds that overcome this constraint is therefore a major challenge in the development of pharmaceutical agents. We demonstrate that the NP conjugates studied in this paper may ameliorate the BBB penetration and enrich the drug concentration in the target bypassing the BBB. NPs were prepared using a biopolymer with a double-emulsion solvent evaporation technique and functionalized with folic acid for site-specific targeting. Dox–Erlo NPs and Dox–Erlo-NP conjugates were extensively characterized in vitro for various parameters. Dox–Erlo NPs and Dox–Erlo-NP conjugates incurred a z-average of 95.35 ± 10.25 nm and 110.12 ± 9.2 nm, respectively. The zeta potentials of the Dox–Erlo NPs and Dox–Erlo-NP conjugates were observed at −18.1 mV and −25.1 mV, respectively. A TEM image has shown that the NPs were well-dispersed, uniform, de-aggregated, and consistent. A hemolytic assay confirmed hemocompatibility with the developed formulation and that it can be safely administered. Dox–Erlo-NP conjugates significantly reduced the number of viable cells to 24.66 ± 2.08% and 32.33 ± 2.51% in U87 and C6 cells, respectively, and IC50 values of 3.064 µM and 3.350 µM in U87 and C6 cells were reported after 24 h, respectively. A biodistribution study revealed that a significant concentration of Dox and Erlo were estimated in the brain relative to drug suspension. Dox–Erlo-NP conjugates were also stable for three months. The findings suggest that the developed Dox–Erlo-NP conjugates may be a promising agent for administration in glioma therapy. [ABSTRACT FROM AUTHOR]

• Synthesis of three novel metal complexes based nitazoxanide drugs. • Characterization by molar conductance, spectroscopic techniques, as well as thermal analysis. • Geometric optimization using DFT/ B3LYP and quantum parameters investigation. • Biological studies; DNA binding and molecular docking studies. • Several in vitro bioassays were performed to evaluate the biological activity, antibacterial, antioxidant and cytotoxicity activity. • The efficiency of the novel compounds as antivirals was tested by molecular docking with two COVID-19 receptors. It has been repeatedly reported that nitazoxanide (NTZ) exhibits a wide range of antiviral activities against various viral infections and has shown antimicrobial properties against anaerobic bacteria, helminths and protozoa. To improve these properties, three novel metal complexes were synthesized. The bidentate characteristic of the NTZ ligand was characterized by different spectroscopic techniques, including Fourier transform infrared (FT-IR), thermogravimetric, nuclear magnetic resonance (NMR) and UV − visible spectroscopy. The geometries of the formed compounds were evaluated by density functional theory, and the results revealed that NTZ-Ru(III) has an octahedral geometry, while NTZ-Au(III) and NTZ-Ag(I) complexes have distorted square planar structures. Binding between the metal complexes and calf thymus DNA (Ct-DNA) has been studied via absorption spectra. Moreover, human albumen serum (HAS) titration has been carried out to test their susceptibility to interact with a major target molecule via absorption and fluorescence spectroscopic techniques. Several in vitro bioassays were performed to evaluate the biological activity, antibacterial potency against E. coli , antioxidant activity and cytotoxicity of the ligand and the obtained complexes. The results showed that complexes Ru(III) and Au(III) have the highest radical scavenging percentage while the Ag(I) demonstrated the greatest antibacterial activity. Moreover, the metal complexes presented potentially effective against E. coli. Furthermore, compared with NTZ-Ag and the free ligand, the in vitro cytotoxicity assay showed that both NTZ-Ru(III) and NTZ-Au(III) exhibited significant anticancer activity against HeLa cells. The efficiency of the novel compounds as antivirals was tested by molecular docking with two COVID-19 receptors to obtain all interaction details. [ABSTRACT FROM AUTHOR]

Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology. [ABSTRACT FROM AUTHOR]

Microtubules have been an attractive target of cancer drug discovery due to their highly dynamic nature during mitosis. Griseofulvin, a natural antifungal compound, is known to interfere with microtubule dynamics. In the present study, we prepared and analyzed twenty‐seven novel griseofulvin derivatives. Three of these compounds had GI50 values <10 μM (5.74 to 9.7 μM) in breast cancer cell line CAL‐51. The most promising compound ((2S,6'R)‐4'‐(benzhydrylamino)‐7‐chloro‐4,6‐dimethoxy‐6'‐methyl‐3H‐spiro[benzofuran‐2,1'‐cyclohexan]‐3'‐ene‐2',3‐dione), was characterized as a microtubule‐stabilizing agent with a GI50 value of 5.74±1.43 μM compared to 10.79±3.06 μM GI50 for parental griseofulvin. It also inhibited the proliferation of other cancer cell lines, including KB‐3‐1 and HCT116, with GI50 values of 1.19±0.34 μM and 2.48±0.40 μM, respectively. Treatment of cancer cells with it resulted in aberrant mitosis causing G2/M arrest. Finally, we show that this compound increased the expression of p53 protein and induced apoptotic cell death. [ABSTRACT FROM AUTHOR]

A set of dinuclear copper(I) complexes with the general formula [Cu2(μ-dppm)2(N^N)2]2+ were synthesized and characterized by 1HNMR, 31PNMR, and elemental analysis. The high-resolution mass spectra clearly illustrated isotopic pattern for the proposed dinuclear systems. The binding of the complexes toward human serum albumin (HSA) were evaluated, highlighting good binding affinities influenced by the nature of the substituted-diimine. The complexes induce changes in both the α-helix and the microenvironment structures of HSA. The HSA-bindings were modelled by molecular docking; [Cu2(μ-dppm)2(dppz)2][ClO4]2 (3) displays the highest binding score toward HSA due to the ability of dppz in establishing π-interactions. The anticancer properties of 1, 2 and 3 were screened against COLO 205, RCC-PR, HepGII and LLC-MK2 cell lines and the results were discussed. Complex 3 has better IC50 against all the cancer cell lines than that observed for cisplatin, but still lower than the cytotoxicity of Sunitinib. Moreover, complex 3 has higher selectivity towards cancer cells over normal cells when compared to cisplatin and sunitinib. [ABSTRACT FROM AUTHOR]

Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 μg/mL, compared to celecoxib drug (IC50 value 251.2 μg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1β. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 μg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

We studied the kinetics of intercalation of a fluorescent probe (rhodamine B (RhB)) during the formation of hierarchal microspheres of cadmium-aluminum layered double hydroxide (CdAlA LDH) and its de-intercalation upon transformation from the LDH phase into the cadmium hydroxide β phase (Cd(OH)2) using a reaction-diffusion framework (RDF) where the hydroxide anions diffuse into an agar gel matrix containing the proper salts-fluorescent probe mixture. In this framework, we achieved the stabilization of the CdAlA LDH, which is known to be thermodynamically unstable and transforms into Cd(OH)2 and Al(OH)3 in a short period. RDF is advantageous as it allows with ease the extraction of the cosynthesized polymorphs and their characterization using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), solid-state nuclear magnetic resonance (SSNMR), Fourier transform infrared (FT-IR), and energy dispersive X-ray (EDX). The kinetics of inter/de-intercalation is studied using in situ steady-state fluorescence measurements. The existence of RhB between the LDH layers and its expel during the transition into the β phase are examined via fluorescence microscopy, XRD, and SSNMR. The activation energies of intercalation and de-intercalation of RhB are determined and show dependence on the cationic ratio of the corresponding LDH. We find that the energies of de-intercalation are systematically higher than those of intercalation, indicating that the dyes are stabilized due to the probe-brucite sheets interactions. SSNMR is used to shed light on the mechanism of intercalation and stabilization of RhB inside the layers of the LDH. [ABSTRACT FROM AUTHOR]

The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds. [Display omitted] • Phytoconstituents show promise in diabetic wound healing by inhibiting NF-κB, with lower toxicity and better safety. • NF-kB in diabetic wound healing coordinates cytokine secretion, growth factor release, and cell proliferation. • NF-κB is regulated by inhibitors like IκBα, IκBβ, and IκBγ, maintaining NF-κB pathway inactivation. [ABSTRACT FROM AUTHOR]