Pharmacological characterization of a novel putative nootropic beta-alanine derivative, MB-005, in adult zebrafish.

BACKGROUND: Cognitive deficits represent an urgent biomedical problem, and are commonly reduced by nootropic drugs. Animal models, including both rodents and zebrafish, offer a valuable tool for studying cognitive phenotypes and screening novel nootropics. Beta-alanine and its derivatives have recently been proposed to exert nootropic activity. AIMS: This study aimed to characterize putative nootropic profile of a novel ß-alanine analogue, 1,3-diaminopropane (MB-005), in adult zebrafish. METHODS: Nootropic profile of MB-005 was assessed in adult zebrafish in the novel tank and conditioned place aversion (CPA) tests acutely, and in cued-learning plus-maze (PMT) tests chronically. RESULTS/OUTCOMES: MB-005 did not alter zebrafish anxiety-like behavior or monoamine neurochemistry acutely, improved short-term memory in the CPA test, but impaired cognitive performance in both CPA and PMT tests chronically. CONCLUSIONS/INTERPRETATION: This study reveals high sensitivity of zebrafish cognitive phenotypes to MB-005, suggesting it as a potential novel cognitive enhancer acutely, but raises concerns over its cognitive (and, possibly, other) side-effects chronically.

Unsymmetrical Trifluoromethyl Methoxyphenyl ß-Diketones: Effect of the Position of Methoxy Group and Coordination at Cu(II) on Biological Activity.

Copper(II) complexes with 1,1,1-trifluoro-4-(4-methoxyphenyl)butan-2,4-dione (HL1) were synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single crystal X-ray diffraction. The biological properties of HL1 and cis-[Cu(L1)2(DMSO)] (3) were examined against Gram-positive and Gram-negative bacteria and opportunistic unicellular fungi. The cytotoxicity was estimated towards the HeLa and Vero cell lines. Complex 3 demonstrated antibacterial activity towards S. aureus comparable to that of streptomycin, lower antifungal activity than the ligand HL1 and moderate cytotoxicity. The bioactivity was compared with the activity of compounds of similar structures. The effect of changing the position of the methoxy group at the aromatic ring in the ligand moiety of the complexes on their antimicrobial and cytotoxic activity was explored. We propose that complex 3 has lower bioavailability and reduced bioactivity than expected due to strong intermolecular contacts. In addition, molecular docking studies provided theoretical information on the interactions of tested compounds with ribonucleotide reductase subunit R2, as well as the chaperones Hsp70 and Hsp90, which are important biomolecular targets for antitumor and antimicrobial drug search and design. The obtained results revealed that the complexes displayed enhanced affinity over organic ligands. Taken together, the copper(II) complexes with the trifluoromethyl methoxyphenyl-substituted ß-diketones could be considered as promising anticancer agents with antibacterial properties.

Biological activity and synthesis of 5,6-dihydroxyindole-2-carboxylic acid - biosynthetic precursor of melanins (microreview).

The microreview considers the biological activity and methods of obtaining natural melanin pigments and their biosynthetic precursor 5,6-dihydroxyindole-2-carboxylic acid. The key methods for the synthesis of 5,6-dihydroxyindole-2-carboxylic acid, published over the past 8 years (2012-2020), are presented.

Interfacial Electrostatic Properties of Hydrated Mesoporous and Nanostructured Alumina Powders by Spin Labeling EPR.

Acid-base equilibria and interfacial electrostatic properties of hydrated mesoporous and nanostructured alumina powders are determining factors for the use of these materials in heterogeneous catalysis and as a sorption media for filtration and chromatographic applications including life sciences. Here spin probe electron paramagnetic resonance spectroscopy of pH-sensitive nitroxides was employed to evaluate the surface charge and interfacial acid-base equilibria at the pore surface of mesoporous powders of α-Al2O3, γ-Al2O3, Al2O3 × nH2O, and basic γ-Al2O3 and nanostructured Al2O3 in the form of pristine materials and modified with aluminum-tri-sec-butoxide, hydroxyaluminum glycerate, and several phospholipids. A new pH-sensitive nitroxide probe, 4-dimethylamino-5,5-dimethyl-2-(4-(chloromethyl)phenyl)-2-ethyl-2,5-dihydro-1H-imidazol-1-oxyl hydrochloride semihydrate (nitroxide R1), has been synthesized and characterized. It was found that conditions of preparation of alumina powders exert strikingly large effects on the apparent pK a of nitroxides measured from electron paramagnetic resonance titration curves. Specifically, while the electron paramagnetic resonance titrations curves for the nitroxide R1 in mesoporous powders prepared from basic γ-Al2O3 and Al2O3 × nH2O were shifted by ΔpK a≈ +0.6 and up to ≈ +1.2 pH units respectively, the shift for γ-Al2O3 was found to be much higher: ΔpK a = +3.5. Assuming approximately the same ∆pH = 0.5-1.0 arising from a difference in the hydrogen ion activity between the bulk solution phase and that in a confined pore volume, the samples were ranked in the following order of descending magnitude of the effective surface electrostatic potential Ψ: mesoporous γ-Al2O3 > Al2O3 × nH2O > basic γ-Al2O3 > α-Al2O3. Conditions of the Al2O3 synthesis as well as the surface modification procedures were found to have profound effects on the interfacial electrostatic properties of hydrated samples that are likely related to the nature and concentration of the active sites on the alumina surfaces.

Imidazolyl derivative of chitosan with high substitution degree: Synthesis, characterization and sorption properties.

A method of synthesis of chitosan imidazolyl derivative - N-(5-methyl-4-imidazolyl)methylchitosan (IM-chitosan) with high degree of substitution (DS) via reaction with 5-methyl-4-imidazolylmethanol has been developed. This method enables one to obtain polymers with the DS up to 1.35 with simultaneous cross-linkage of the matrix. The chemical structure of the obtained IM-chitosan was characterized by FT-IR, (13)C and (15)N NMR spectroscopies. It was shown that cross-linkage of IM-chitosans occurred due to formation of N-glucoside derivatives. Sorption capacities of IM-chitosans toward transition metal ions have an extremal dependence on DS, which is less pronounced for Ag(I) ions in comparison with Cu(II) and Ni(II) ions. The decrease of sorption capacities for derivatives with DS 0.5-1.0 is attributed to steric hindrances for ion-binding due to increased stiffness of the polymer matrix at high DS as a result of cross-linking. Sorption capacities of IM-chitosans toward noble metal ions in 0.1M HCl gradually increase with DS, since higher swelling polymers in acidic media eliminates negative effect of cross-linking on availability of sorption sites.

Carboxyalkylation of chitosan in the gel state.

This study presents a new approach for direct carboxyalkylation of chitosan in the gel state by using aza-Michael addition and substitution reactions. Various reagents were applied including acrylic and crotonic acids, and α-, ß-, γ-, δ-, and ɛ-halocarboxylic acids. The reaction of chitosan with γ- and δ-halocarboxylic acids showed no target product formation either in solution or in the gel state. In the case of acrylic, crotonic, α- and ß-halocarboxylic acids, the reaction performed in the gel state (concentration of chitosan 20-40%) shows higher degree of substitution at lower reaction time and temperature than in diluted solutions (concentration of chitosan 0.5-2%). The results were discussed in terms of kinetics of the target and side reactions. (1)H and (13)C NMR confirmed that in all cases the carboxyalkylation of chitosan proceeds exclusively at the amino groups.

Evaluation of various chitin-glucan derivatives from Aspergillus niger as transition metal adsorbents.

A number of chelating resins were prepared by chemical derivatization of the chitin-glucan (CG) complex isolated from Aspergillus niger biomass, namely chitosan-glucan (CsG), O-carboxymethyl-chitin-glucan (CM-CG), O-(2-sulfoethyl)chitin-glucan (SE-CG), and N-(2-carboxyethyl)chitosan-glucan (CE-CsG). The chemical modification was confirmed by FT-IR and elemental analysis. Nanosecond electron beam irradiation was used to produce insoluble resins and to preserve the reactive functional groups. Batch experiments were carried out to evaluate the adsorption selectivity and capacity of the resins toward transition metal ions (Cu(2+), Ni(2+), Co(2+), Zn(2+)). The resins showed good adsorption capability with the following selectivity series: Co(2+)Zn(2+). The total metal adsorption capacities of CG, CsG, CM-CG, SE-CG, and CE-CsG resins at pH 6.5 (ammonium acetate buffer) were found to be 0.205, 0.382, 1.752, 0.319, and 0.350 mmol g(-1), respectively. Our results suggest that, depending on the type of chemical modification, the chitin-glucan complexes can be used either for selective Cu(2+) removal (CsG) or for total transition metal adsorption (CM-CG) from aqueous effluents.

Bis[N-(2-hydroxyethyl)-beta-alaninato]copper(II).

The Cu(II) ion in the title complex, [Cu(C5H10NO3)2] or [Cu(He-ala)2] [He-ala = N-(2-hydroxyethyl)-beta-alaninate], resides at the inversion centre of a square bipyramid comprised of two facially arranged tridentate He-ala ligands. Each He-ala ligand binds to a Cu(II) ion by forming one six-membered beta-alaninate chelate ring in a twist conformation and one five-membered ethanolamine ring in an envelope conformation, with Cu-N = 2.017 (2) angstroms, Cu-O(COO) = 1.968 (1) angstroms and Cu-O(OH) = 2.473 (2) angstroms. The [Cu(He-ala)2] molecules are involved in a network of O-H...O and N-H...O hydrogen bonds, forming layers parallel to the (10-1) plane. The layers are connected into a three-dimensional structure by van der Waals interactions, so that the molecular centres form pseudo-face-centered close packing.