New Library of Iodo-Quinoline Derivatives Obtained by an Alternative Synthetic Pathway and Their Antimicrobial Activity.

6-Iodo-substituted carboxy-quinolines were obtained using a one-pot, three-component method with trifluoroacetic acid as a catalyst under acidic conditions. Iodo-aniline, pyruvic acid and 22 phenyl-substituted aldehydes (we varied the type and number of radicals) or O-heterocycles, resulting in different electronic effects, were the starting components. This approach offers advantages such as rapid response times, cost-effective catalysts, high product yields and efficient purification procedures. A comprehensive investigation was conducted to examine the impact of aldehyde structure on the synthesis pathway. A library of compounds was obtained and characterized by FT-IR, MS, 1H NMR and 13C NMR spectroscopy and single-ray crystal diffractometry. Their antimicrobial activity against S. epidermidis, K. pneumonie and C. parapsilosis was tested in vitro. The effect of iodo-quinoline derivatives on microbial adhesion, the initial stage of microbial biofilm development, was also investigated. This study suggests that carboxy-quinoline derivatives bearing an iodine atom are interesting scaffolds for the development of novel antimicrobial agents.

Synthesis and Biological Properties of Fluorescent Strigolactone Mimics Derived from 1,8-Naphthalimide.

Strigolactones (SLs) have potential to be used in sustainable agriculture to mitigate various stresses that plants have to deal with. The natural SLs, as well as the synthetic analogs, are difficult to obtain in sufficient amounts for practical applications. At the same time, fluorescent SLs would be useful for the mechanistic understanding of their effects based on bio-imaging or spectroscopic techniques. In this study, new fluorescent SL mimics containing a substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive furan-2-one moiety were prepared. The structural, spectroscopic, and biological activity of the new SL mimics on phytopathogens were investigated and compared with previously synthetized fluorescent SL mimics. The chemical group at the C-6 position of the naphthalimide ring influences the fluorescence parameters. All SL mimics showed effects similar to GR24 on phytopathogens, indicating their suitability for practical applications. The pattern of the biological activity depended on the fungal species, SL mimic and concentration, and hyphal order. This dependence is probably related to the specificity of each fungal receptor-SL mimic interaction, which will have to be analyzed in-depth. Based on the biological properties and spectroscopic particularities, one SL mimic could be a good candidate for microscopic and spectroscopic investigations.

Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure-Activity Relationship.

The paper aims to investigate the antitumor activity of a series of phenothiazine derivatives in order to establish a structure-antitumor activity relationship. To this end, PEGylated and TEGylated phenothiazine have been functionalized with formyl units and further with sulfonamide units via dynamic imine bonds. Their antitumor activity was monitored in vitro against seven human tumors cell lines and a mouse one compared to a human normal cell line by MTS assay. In order to find the potential influence of different building blocks on antitumor activity, the antioxidant activity, the ability to inhibit farnesyltransferase and the capacity to bind amino acids relevant for tumor cell growth were investigated as well. It was established that different building blocks conferred different functionalities, inducing specific antitumor activity against the tumor cells.

Synthesis and Solvent Dependent Fluorescence of Some Piperidine-Substituted Naphthalimide Derivatives and Consequences for Water Sensing.

Novel fluorescent strigolactone derivatives that contain the piperidine-substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive 3-methyl-furan-2-one unit were synthesized and their spectroscopic properties investigated. The solvatochromic behavior of these piperidine-naphthalimides was monitored in solvents of different polarity using the electronic absorption and fluorescence spectra. These compounds exhibited a strong positive solvatochromism taking into account the change of solvent polarity, and the response mechanism was analyzed by fluorescence lifetime measurements. According to Catalan and [f(n), f(ε), ß, α] solvent scales, the dipolarity and polarizability are relevant to describe the solute-solvent interactions. The emission chemosensing activity was discussed in order to determine the water content in organic environments. The emission intensity of these compounds decreased rapidly in dioxane, increasing water level up to 10%. Measuring of quantum yield indicated that the highest values of quantum efficiency were obtained in nonpolar solvents, while in polar solvents these derivatives revealed the lowest quantum yield. The fluorescence decay can be described by a monoexponential model for low water levels, and for higher water contents a biexponential model was valid.

Some Theoretical and Experimental Evidence for Particularities of the Siloxane Bond.

The specific features of the siloxane bond unify the compounds based on it into a class with its own chemistry and unique combinations of chemical and physical properties. An illustration of their chemical peculiarity is the behavior of 1,3-bis(2-aminoethylaminomethyl)tetramethyldisiloxane (AEAMDS) in the reaction with carbonyl compounds and metal salts, by which we obtain the metal complexes of the corresponding Schiff bases formed in situ. Depending on the reaction conditions, the fragmentation of this compound takes place at the siloxane bond, but, in most cases, it is in the organic moieties in the ß position with respect to the silicon atom. The main compounds that were formed based on the moieties resulting from the splitting of this diamine were isolated and characterized from a structural point of view. Depending on the presence or not of the metal salt in the reaction mixture, these are metal complexes with organic ligands (either dangling or not dangling silanol tails), or organic compounds. Through theoretical calculations, electrons that appear in the structure of the siloxane bond in different contexts and that lead to such fragmentations have been assessed.

Nitrogen-Based Linkers with a Mesitylene Core: Synthesis and Characterization.

Mesitylene was used as a core in seven new tritopic nitrogen containing linkers. Three of the linkers, each containing three nitrile groups, were obtained through Suzuki, Sonogashira and Heck-type coupling reactions. Next, these were converted to tetrazol-5-yl moieties by the cycloaddition of sodium azide to the nitrile functionalities. The last linker, containing three 1,2,3-triazol-4-yl moieties, was synthesized by the Huisgen cycloaddition of phenyl azide to the corresponding alkyne. The latter was obtained via a Corey-Fuchs reaction sequence from the previously reported formyl derivative. As the proof of concept for their potential in MOF design, one of the nitriles was used to build an Ag-based network.

Antioxidant, Cytotoxic and Antimicrobial Activity of Chitosan Preparations Extracted from Ganoderma Lucidum Mushroom.

Two chitosan extracts were prepared by chemical and enzymatic treatment of Ganoderma lucidum mushroom, as an alternative source to crustacean shells. The molecular weight of the enzymatic extract was lower than that of the chemical one and of shrimp chitosan, as determined by viscosity measurements. Characteristic signals were identified in the 1 H-NMR spectra and high deacetylation degree indicated good physico-chemical properties for both mushroom chitosan extracts. The scavenging capacity of mushroom chitosan extracts was moderate against the synthetic radicals of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), but higher values were observed for the enzymatic extract, compared to the chemical extract and shrimp chitosan. In vitro cytotoxicity was evaluated in L929 mouse fibroblast cell lines and the results of MTT assay showed good cytocompatibility in the tested range of concentrations. The growth of Gram-positive bacteria was inhibited more than Gram-negative bacteria in the presence of mushroom chitosan extracts, in particular by the chemical one, indicating their efficiency as antimicrobial agents. All these results strengthen the evidence of mushroom polysaccharide preparations availability for biomedical applications.

Monitoring Methylmalonic Aciduria by NMR Urinomics.

The paper reports on monitoring methylmalonic aciduria (MMA)-specific and non-specific metabolites via NMR urinomics. Five patients have been monitored over periods of time; things involved were diet, medication and occasional episodes of failing to comply with prescribed diets. An extended dataset of targeted metabolites is presented, and correlations with the type of MMA are underlined. A survey of previous NMR studies on MMA is also presented.

Chemical Profile and Antioxidant Activity of Zinnia elegans Jacq. Fractions.

Zinnia elegans (syn. Zinnia violacea) is a common ornamental plant of the Asteraceae family, widely cultivated for the impressive range of flower colors and persistent bloom. Given its uncomplicated cultivation and high adaptability to harsh landscape conditions, we investigated the potential use of Z. elegans as a source of valuable secondary metabolites. Preliminary classification of compounds found in a methanolic extract obtained from inflorescences of Z. elegans cv. Caroussel was accomplished using HR LC-MS techniques. The extract was then subjected to solid-phase extraction and separation using Sephadex LH-20 column chromatography, which resulted in several fractions further investigated for their antioxidant properties through lipoxygenase inhibition and metal chelating activity assays. Moreover, following additional purification procedures, structures of some active ingredients were established by NMR spectroscopy. The investigated fractions contained polyphenolic compounds such as chlorogenic acids and apigenin, kaempferol, and quercetin glycosides. Antioxidant assays showed that certain fractions exhibit moderate 15-LOX inhibition (Fr 2, IC50 = 18.98 µg/mL) and metal chelation (e.g., Fr 1-2, EC50 = 0.714-1.037 mg/mL) activities as compared to positive controls (20.25 µg/mL for kaempferol and 0.068 mg/mL for EDTA, respectively). For Fr 2, the 15-LOX inhibition activity seems to be related to the abundance of kaempferol glycosides. The NMR analyses revealed the presence of a kaempferol 3-O-glycoside, and a guanidine alkaloid previously not described in this species.

Novel Mutation in GALT Gene in Galactosemia Patient with Group B Streptococcus Meningitis and Acute Liver Failure.

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) involved in galactose metabolism. Bacterial infections are a known cause of early morbidity and mortality in children with classic galactosemia. The most common agent is Escherichia coli, but in rare situations, other bacteria are incriminated. We report a case of a three-week-old female patient with galactosemia, who presented with Group B Streptococcus (GBS) meningitis/sepsis. She received treatment with antibiotics, supportive therapy, and erythrocyte transfusion, but after a short period of improvement, she presented acute liver failure with suspicion of an inborn error of metabolism. Rapid nuclear magnetic resonance (NMR) spectroscopy from urine showed highly elevated values of galactose and galactitol. Under intensive treatment for acute liver failure and with a lactose-free diet, her clinical features and laboratory parameters improved considerably. Genetic testing confirmed compound heterozygous status for GALT mutations: c.563 A>G [p.Q188R] and c. 910 C>T, the last mutation being a novel mutation in GALT gene. In countries without an extensive newborn screening program, a high index of suspicion is necessary for early diagnosis and treatment of galactosemia.

Hyperpolarised NMR to follow water proton transport through membrane channels via exchange with biomolecules.

Water uptake in vesicles and the subsequent exchange between water protons and amide -NH protons in amino acids can be followed by a new, highly sensitive, type of magnetic resonance spectroscopy: dynamic nuclear polarisation (DNP)-enhanced NMR in the liquid state. Water hydrogen atoms are detected prior to and after their transfer to molecular sites in peptides and proteins featuring highly-accessible proton-exchangeable groups, as is the case for the -NH groups of intrinsically disordered proteins. The detected rates for amide proton-water proton exchange can be modulated by membrane-crossing rates, when a membrane channel is interposed. We hyperpolarised water proton spins via dynamic nuclear polarisation followed by sample dissolution (d-DNP) and transferred the created polarisation to -NH groups with high solvent accessibility in an intrinsically disordered protein domain. This domain is the membrane anchor of c-Src kinase, whose activity controls cell proliferation. The hindrance of effective water proton transfer rate constants observed in free solvent when a membrane-crossing step is involved is discussed. This study aims to assess the feasibility of recently-introduced hyperpolarised (DNP-enhanced) NMR to assess water membrane crossing dynamics.

New Strigolactone Mimics as Exogenous Signals for Rhizosphere Organisms.

The importance of strigolactones in plant biology prompted us to synthesize simplified strigolactone mimics effective as exogenous signals for rhizosphere organisms. New strigolactone mimics easily derived from simple and available starting materials in significant amounts were prepared and fully characterized. These compounds contain an aromatic or heterocyclic ring, usually present in various bioactive molecules, connected by an ether link to a furan-2-one moiety. The new synthesized strigolactone mimics were confirmed to be active on plant pathogenic fungi and parasitic weed seeds.

Isoxazole derivatives as new nitric oxide elicitors in plants.

Several 3,5-disubstituted isoxazoles were obtained in good yields by regiospecific 1,3-dipolar cycloaddition reactions between aromatic nitrile oxides, generated in situ from the corresponding hydroxyimidoyl chlorides, with non-symmetrical activated alkynes in the presence of catalytic amounts of copper(I) iodide. Effects of 3,5-disubstituted isoxazoles on nitric oxide and reactive oxygen species generation in Arabidopsis tissues was studied using specific diaminofluoresceine dyes as fluorescence indicators.

Out-of-water constitutional self-organization of chitosan-cinnamaldehyde dynagels.

An investigation of the constitutional adaptive gelation process of chitosan/cinnamaldehyde (C/Cy) dynagels is reported. These gels generate timely variant macroscopic organization across extended scales. In the first stage, imine-bond formation takes place "in-water" and generates low-ordered hydrogels. The progressive formation of imine bonds further induces "out-of-water" increased reactivity within interdigitated hydrophobic self-assembled layers of Cy, with a protecting environmental effect against hydrolysis and that leads to the stabilization of the imine bonds. The hydrophobic swelling due to Cy layers at the interfaces reaches a critical step when lamellar self-organized hybrids are generated (24 hours). This induces an important restructuration of the hydrogels on the micrometric scale, thus resulting in the formation of highly ordered microporous xerogel morphologies of high potential interest for chemical separations, drug delivery, and sensors.

A facile synthesis of Pechmann dyes.

A facile synthesis of Pechmann dyes has been accomplished by the reaction of substituted N-phenacyl-4-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU. Based on a related 4-DMAP elimination product and an isolated monolactone intermediate a reaction mechanism has been proposed. The scope of this synthetic method is determined by the availability of α-haloaroyl or heteroaroyl derivatives. DBU=1,8-diazabicycloundec-7-ene, DMAP=4-dimethylaminopyridine.

Low toxicity ß-cyclodextrin-caged 4,4'-bipyridinium-bis(siloxane): synthesis and evaluation.

The toxicity of viologens can be significantly reduced by including them in tight [2]rotaxane structures alongside ß-cyclodextrin, thus turning them into candidates of pharmaceutical interest. Here, we report a synthesis pathway for a benign viologen, by capping a small ß-cyclodextrin-caged molecule, the 4,4'-bipyridine, with minimal-length presynthesized axle-stopper segments of the propyl-3-pentamethyldisiloxane type. After 90 min from the oral administration to laboratory mice, the product concentration in the bloodstream reaches a value equivalent to 0.634% of the initial dose of 800 mg·kg(-1). As compared to the nude viologen having the same structure, which proved to be lethal in doses of 40 mg·kg(-1), the product induces reversible morphological changes in the liver, kidney, lung, and cerebellum, up to a dose of 400 mg·kg(-1), with higher dosages giving rise to a chronic slow evolution.

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones.

The one-pot three-component reactions of 1-substituted benzimidazoles with ethyl bromoacetate and electron-deficient alkynes, in 1,2-epoxybutane, gave a variety of pyrrolo[1,2-a]quinoxalin-4-ones and pyrrolo[1,2-a]benzimidazoles. The influence of experimental conditions on the course of reaction was investigated. A novel synthetic pathway starting from benzimidazoles unsubstituted at the five membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature, led directly to pyrrolo[1,2-a]quinoxalin-4-ones in fair yield by an one-pot three-component reaction.

NMR Spectroscopy in Diagnosis and Monitoring of Methylmalonic and Propionic Acidemias.

Although both localized nuclear magnetic resonance spectroscopy (MRS) and non-localized nuclear magnetic resonance spectroscopy (NMR) generate the same information, i.e., spectra generated by various groups from the structure of metabolites, they are rarely employed in the same study or by the same research group. As our review reveals, these techniques have never been applied in the same study of methylmalonic acidemia (MMA), propionic acidemia (PA) or vitamin B12 deficiency patients. On the other hand, MRS and NMR provide complementary information which is very valuable in the assessment of the severity of disease and efficiency of its treatment. Thus, MRS provides intracellular metabolic information from localized regions of the brain, while NMR provides extracellular metabolic information from biological fluids like urine, blood or cerebrospinal fluid. This paper presents an up-to-date review of the NMR and MRS studies reported to date for methylmalonic and propionic acidemias. Vitamin B12 deficiency, although in most of its cases not inherited, shares similarities in its metabolic effects with MMA and it is also covered in this review.

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety.

New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (KI 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (KI 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.

Unexpected formation of N-(1-(2-aryl-hydrazono)isoindolin-2-yl)benzamides and their conversion into 1,2-(bis-1,3,4-oxadiazol-2-yl)benzenes.

Reaction between ortho-phthalaldehyde and various aroylhydrazines unexpectedly yields N-(1-(2-aryl-hydrazono)isoindolin-2-yl)benzamides as major products along with the predictable 1,2-bis-aroylhydrazones. NMR investigation of the major reaction products indicate the presence of a mixture of geometrical isomers, in various ratios. Single crystal X-ray diffraction confirms the proposed structure and indicates a Z configuration of the C═N double bond substitutents. Optimization of the condensation reaction conditions enabled quantitative isolation of the cyclic isomer. Oxidation of the isomers with bis(trifluoroacetoxy)iodobenzene (PIFA) leads to rapid formation of new highly fluorescent 1,2-bis(5-aryl-1,3,4-oxadiazol-2-yl)benzenes.