Synthesis of Cobalt Bis(Dicarbollide)—Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).     

Extracts from European Propolises as Potent Tyrosinase Inhibitors

Tyrosinase is a key enzyme in the melanogenesis pathway. Melanin, the product of this process, is the main pigment of the human skin and a major protection factor against harmful ultraviolet radiation (UVR). Increased melanin synthesis due to tyrosinase hyperactivity can cause hyperpigmentation disorders, which in consequence causes freckles, age spots, melasma, or postinflammatory hyperpigmentation. Tyrosinase overproduction and hyperactivity are triggered by the ageing processes and skin inflammation as a result of oxidative stress. Therefore, the control of tyrosinase activity is the main goal of the prevention and treatment of pigmentation disorders. Natural products, especially propolis, according to their phytochemical profile abundant in polyphenols, is a very rich resource of new potential tyrosinase inhibitors. Therefore, this study focused on the assessment of the tyrosinase inhibitory potential of six extracts obtained from the European propolis samples of various origins. The results showed the potent inhibitory activity of all tested propolis extracts towards commercially available mushroom tyrosinase. The four most active propolis extracts showed inhibitory activity in the range of 86.66–93.25%. Apart from the evaluation of the tyrosinase inhibition, the performed research included UHPLC–DAD–MS/MS (ultra high performance liquid chromatography coupled with diode array detection and tandem mass spectrometry) phytochemical profiling as well as antioxidant activity assessment using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2”-azino-bis(3-ethylbenzothiazoline-6-sulfuric acid (ABTS) radical scavenging tests. Moreover, statistical analysis was used to correlate the tyrosinase inhibitory and antioxidant activities of propolis extracts with their phytochemical composition. To summarise, the results of our research showed that tested propolis extracts could be used for skin cosmeceutical and medical applications.     

Effect of Poly(methacrylic acid) on the Cytokine Level in an In Vivo Tumor Model

Cancer is a leading cause of mortality globally. Despite remarkable improvements in cancer-treatment approaches, disease recurrence and progression remain major obstacles to therapy. While chemotherapy is still a first-line treatment for a variety of cancers, the focus has shifted to the development and application of new approaches to therapy. Nevertheless, the relationship between immune response, neoplastic diseases and treatment efficiency is not fully understood. Therefore, the aim of the study was to investigate the immunopharmacological effects of methacrylic acid homopolymer in an in vivo tumor model. Materials and methods: Monomeric methacrylic acid was used to synthesize polymers. Methacrylic acid was polymerized in dioxane in the presence of 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid. To study the molecular weight characteristics of PMAA by GPC, carboxyl groups were preliminarily methylated with diazomethane. An experimental cancer model was obtained by grafting RMK1 breast cancer cells. The serum levels of IL-6, IL-10, IL-17, transforming growth factor β1 (TGF-β1), and tumor necrosis factor α (TNF-α) were measured by ELISA. Results: The effect of PMAA on the serum concentrations of several cytokines was studied upon its single administration to laboratory animals in early neoplastic process. The IL-6, IL-17 and TGF-β1 concentrations were found to change significantly and reach the level observed in intact rats. The IL-10 concentration tended to normalize. Conclusion: The positive results obtained are the basis for further studies on the effect of methacrylic-acid polymers with different molecular-weight characteristics on the neoplastic process.     

Conjugates of Iron-Transporting N-Hydroxylactams with Ciprofloxacin

Screening of a library of novel N-hydroxylactams amenable by the Castagnoli-Cushman reaction identified four lead compounds that facilitated ⁵⁵Fe transport into P. aeruginosa cells (one of these synthetic siderophores was found to be as efficient at promoting iron uptake as the natural siderophores pyoverdine, pyochelin or enterobactin). Conjugates of the four lead siderophores with ciprofloxacin were tested for antibacterial activity against P. aeruginosa POA1 (wild type) and the ∆pvdF∆pchA mutant strain. The antibacterial activity was found to be pronounced against the ∆pvdF∆pchA mutant strain grown in CAA medium but not for the POA1 strain. This may be indicative of these compounds being ‘Trojan horse’ antibiotics. Further scrutiny of the mechanism of the antibacterial action of the newly developed conjugates is warranted.     

Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC_0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development.     

The Effect of Blood Contained in the Samples on the Metabolomic Profile of Mouse Brain Tissue: A Study by NMR Spectroscopy

(1) Recently, metabolic profiling of the tissue in the native state or extracts of its metabolites has become increasingly important in the field of metabolomics. An important factor, in this case, is the presence of blood in a tissue sample, which can potentially lead to a change in the concentration of tissue metabolites and, as a result, distortion of experimental data and their interpretation. (2) In this paper, the metabolomic profiling based on NMR spectroscopy was performed to determine the effect of blood contained in the studied samples of brain tissue on their metabolomic profile. We used 13 male laboratory CD-1^® IGS mice for this study. The animals were divided into two groups. The first group of animals (n = 7) was subjected to the perfusion procedure, and the second group of animals (n = 6) was not perfused. The brain tissues of the animals were homogenized, and the metabolite fraction was extracted with a water/methanol/chloroform solution. Samples were studied by high-frequency ¹H-NMR spectroscopy with subsequent statistical data analysis. The group comparison was performed with the use of the Student’s test. We identified 36 metabolites in the brain tissue with the use of NMR spectroscopy. (3) For the major set of studied metabolites, no significant differences were found in the brain tissue metabolite concentrations in the native state and after the blood removal procedure. (4) Thus, it was shown that the presence of blood does not have a significant effect on the metabolomic profile of the brain in animals without pathologies.     

Optimization of the cathode porosity via mechanochemical synthesis with carbon black

Journal of Solid State Electrochemistry - Nanostructured carbon–coated composite cathode materials LiFe0.5Mn0.5PO4/C (LFMP/C) are prepared by the mechanochemically assisted solid-state...     

New Bio-Based Furanic Materials Effectively Absorb Metals from Water and Exert Antimicrobial Activity

Development of sustainable bio-based materials for removal of toxic contaminants from water is a high priority goal. Novel bio-based binary and ternary copolymers with enhanced ion-exchange, adsorption and antibacterial properties were obtained by using plant biomass-derived diallyl esters of furandicarboxylic acid (FDCA) as crosslinking agents and easily available vinyl monomers. The synthesized copolymer materials showed higher sorption capacities for Ni^II, Co^II and Cu^II compared to the commercial ion-exchange resins, and they maintained their high metal adsorption capacities for over 10 cycles of regeneration. The synthesized copolymer gels containing 1–5 wt % of the crosslinker showed excellent water absorption capacities. The synthesized copolymers with 1 % crosslinker content showed swelling ratios high enough to also act as moisture absorbents. Synthesized copolymers with crosslinker content of 10 wt % performed as contact-active antibacterials by inhibiting the growth of Gram-positive (S. aureus) and Gram-negative bacteria (E. coli, K. pneumonia) in suspension tests.     

Mono- and Diamination of 4,6-Dichloropyrimidine, 2,6-Dichloropyrazine and 1,3-Dichloroisoquinoline with Adamantane-Containing Amines

N-heteroaryl substituted adamantane-containing amines are of substantial interest for their perspective antiviral and psychotherapeutic activities. Chlorine atom at alpha-position of N-heterocycles has been substituted by the amino group using convenient nucleophilic substitution reactions with a series of adamantylalkylamines. The prototropic equilibrium in these compounds was studied using NMR spectroscopy. The introduction of the second amino substituent in 4-amino-6-chloropyrimidine, 2-amino-chloropyrazine, and 1-amino-3-chloroisoquinoline was achieved using Pd(0) catalysis.     

Destructive adsorption of CCl4 over lanthanum-based solids: linking activity to acid-base properties

The relative activities of a low-surface crystalline and high-surface amorphous LaOCl, further denoted as S1 and S2, have been compared for the destructive adsorption of CCl4. It was found that the intrinsic activity of S2 is higher than that of S1. Both samples were characterized with X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), N2-physisorption, and Raman and infrared (IR) spectroscopy. IR was used in combination with CO2, CO, and methanol as probe molecules. The CO2 experiments showed that different carbonate species are formed on both materials. For S1, a high surface concentration of bidentate carbonate species and a lower concentration of monodentate carbonate were observed. In the case of S2, bulk carbonates were present together with bridged carbonates. CO adsorption shows that S2 and S1 have very similar Lewis acid sites. However, methanol adsorption experiments showed that S2 had a higher number of stronger Lewis acid sites than S1 and that twofold coordinated methoxy species were more strongly bound than threefold coordinated methoxy species. Because of the analogy between methanol dissociation and the removal of the first chlorine atom in the destructive adsorption of CCl4, the sites enabling twofold coordination were likely to be the same Lewis acid sites actively involved in the destructive adsorption of CCl4. La2O3 was less active than the two LaOCl materials, and therefore, the intrinsic activity of the catalyst increases as the strength of the Lewis acid sites increases. S2 contains more chlorine at the surface than S1, which is expressed by the higher number of sites enabling twofold coordination. Moreover, this explains the difference in destructive adsorption capacity for CCl4 that was observed for the samples S1 and S2. Since LaCl3, being the most acidic phase, is not active for the destructive adsorption of CCl4, basic oxygen atoms, however, remain needed to stabilize the reaction intermediate CCl3 as La-O-CCl3.