Synthesis, Characterization, and Antibacterial Activity of Ni-Substituted Krebs-type Sandwich-Tungstobismuthates Functionalized with Amino Acids.

Four new Ni-substituted Krebs-type sandwich-tungstobismuthates, KNi[{Ni(β-ala)(HO)}{Ni(HO)}{Ni(HO)(η-β-ala)}(-β-BiWO)]·49HO , KNa[{Ni(η-L-asp)}(WO)(-β-BiWO)]·36HO·L-asp , KNa[{Ni(gly)(HO)}(WO)(-β-BiWO)]·86HO and KNa[{Ni(η-serinol) (HO)}{Ni(HO)}(-β-BiWO)]·42HO have been synthesized by one-pot solution methods. All compounds have been characterized in the solid state by single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD), elemental and thermogravimetric analyses, and infrared spectroscopy (IR), as well as by UV-vis spectroscopy in solution. The antibacterial activity of all compounds was studied against four bacterial strains by the determination of the minimum inhibitory concentration (MIC).

Novel tetrahydropyrimidinyl-substituted benzimidazoles and benzothiazoles: synthesis, antibacterial activity, DNA interactions and ADME profiling.

A series of tetrahydropyrimidinyl-substituted benzimidazoles attached to various aliphatic or aromatic residues phenoxymethylene were synthesised to investigate their antibacterial activities against selected Gram-positive and Gram-negative bacteria. The influence of the type of substituent at the C-3 and C-4 positions of the phenoxymethylene linker on the antibacterial activity was observed, showing that the aromatic moiety improved the antibacterial potency. Of all the evaluated compounds, benzoyl-substituted benzimidazole derivative 15a was the most active compound, particularly against the Gram-negative pathogens (MIC = 1 μg mL) and (MIC = 2 μg mL).

Screening of Novel Antimicrobial Diastereomers of Azithromycin-Thiosemicarbazone Conjugates: A Combined LC-SPE/Cryo NMR, MS/MS and Molecular Modeling Approach.

A well-known class of antibacterials, 14- and 15-membered macrolides are widely prescribed to treat upper and lower respiratory tract infections. Azithromycin is a 15-membered macrolide antibiotic possessing a broad spectrum of antibacterial potency and favorable pharmacokinetics. Bacterial resistance to marketed antibiotics is growing rapidly and represents one of the major global hazards to human health.

Gut microbiota in mucosa and feces of newly diagnosed, treatment-naïve adult inflammatory bowel disease and irritable bowel syndrome patients.

The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD (Crohn's disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing.

Skin Microbiota in Atopic Dermatitis.

The skin microbiota represents an ecosystem composed of numerous microbial species interacting with each other, as well as with host epithelial and immune cells. The microbiota provides health benefits to the host by supporting essential functions of the skin and inhibiting colonization with pathogens. However, the disturbance of the microbial balance can result in dysbiosis and promote skin diseases, such as atopic dermatitis (AD).

New Bicyclic Azalide Macrolides Obtained by Tandem Palladium Catalyzed Allylic Alkylation/Conjugated Addition Reaction.

Unprecedented tandem allylic alkylation/intermolecular Michael addition was used in the preparation of novel bicyclic azalides. NMR spectroscopy was used not only to unambiguously determine and characterize the structures of these unexpected products of chemical reaction but also to investigate the effect the rigid bicyclic modification has on the conformation of the whole molecule. Thus, some of the macrolides prepared showed antibacterial activity in the range of well-known antibiotic drug azithromycin.

The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside.

The current paradigm of urinary tract infection (UTI) pathogenesis takes into account the contamination of the periurethral space by specific uropathogens residing in the gut, which is followed by urethral colonization and pathogen ascension to the urinary bladder. Consequently, studying the relationship between gut microbiota and the subsequent development of bacteriuria and UTI represents an important field of research. However, the well-established diagnostic and therapeutic paradigm for urinary tract infections (UTIs) has come into question with the discovery of a multifaceted, symbiotic microbiome in the healthy urogenital tract.

Aluminum-Substituted Keggin Germanotungstate [HAl(HO)GeWO]: Synthesis, Characterization, and Antibacterial Activity.

We report on the new monosubstituted aluminum Keggin-type germanotungstate (CHN)[HAlGeWO(HO)]·11HO (), which has been synthesized at room temperature via rearrangement of the dilacunary [γ-GeWO] polyoxometalate precursor. has been characterized thoroughly both in the solid state by single-crystal and powder X-ray diffraction, IR spectroscopy, thermogravimetric analysis, and elemental analysis as well as in solution by cyclic voltammetry (CV) W, Al NMR and UV-vis spectroscopy. A study on the antibacterial properties of and the known aluminum(III)-centered Keggin polyoxotungstates (Al-POTs) α-Na[AlWO] () and Na[Al(AlOH)WO] () revealed enhanced activity for all three Al-POTs against the Gram-negative bacterium (minimum inhibitory concentration (MIC) up to 4 μg mL) and the Gram-positive (MIC up to 128 μg mL) compared to the inactive Al(NO) salt (MIC > 256 μg mL).

Synthesis, Characterization, and Phosphoesterase Activity of a Series of 4f- and 4d-Sandwich-Type Germanotungstates [(-CH)N]H[(M(HO))(γ-GeWO)] (M = Ce, Nd, Gd, Er, = 7; Zr, = 6).

We report on a family of five new 4f- and 4d-doped sandwich-type germanotungstates with the general formula [(-CH)N]H[(M(HO))(γ-GeWO)]·3(CH)CO (M = Ce, Nd, Gd, Er, = 7; Zr, = 6), which have been synthesized at room temperature in an acetone-water mixture. Among the compound series, , which has been obtained in the presence of 30% HO, represents the first example of a 4d-substituted germanotungstate incorporating the intact dilacunary [γ-GeWO] building block. All compounds were characterized thoroughly in the solid state by single-crystal and powder X-ray diffraction (XRD), IR spectroscopy, thermogravimetric analysis (TGA), and elemental analysis and in solution by NMR and UV-vis spectroscopy.

Gut Microbiota beyond Bacteria-Mycobiome, Virome, Archaeome, and Eukaryotic Parasites in IBD.

The human microbiota is a diverse microbial ecosystem associated with many beneficial physiological functions as well as numerous disease etiologies. Dominated by bacteria, the microbiota also includes commensal populations of fungi, viruses, archaea, and protists. Unlike bacterial microbiota, which was extensively studied in the past two decades, these non-bacterial microorganisms, their functional roles, and their interaction with one another or with host immune system have not been as widely explored.

Green synthesis and biological evaluation of 6-substituted-2-(2-hydroxy/methoxy phenyl)benzothiazole derivatives as potential antioxidant, antibacterial and antitumor agents.

We present a new efficient green synthetic protocol for introduction of substituents to the C-6 position of 2-arylbenzothiazole nuclei. Newly synthesized compounds were designed to study the influence of the hydroxy and methoxy groups on the 2-arylbenzothiazole scaffold, as well as the influence of the type of substituents placed on the C-6 position of benzothiazole moiety on biological activity, including antibacterial, antitumor and antioxidant activity. Modest activity was observed against the tested Gram-positive and Gram-negative bacterial strains for only amidino derivatives 5d and 6d.

The Role of Vitamin D in Inflammatory Bowel Disease - Assessing Therapeutic and Preventive Potential of Supplementation and Food Fortification.

Inflammatory bowel diseases are a group of chronic inflammatory conditions that affect gastrointestinal tract due to inapt and continuous immune activation in response to a myriad of predisposing factors (most notably genetics, environmental impact and gut microbiota composition). It has been shown that vitamin D status can also play a role in the disease pathogenesis, as its deficiency is commonly observed in two major forms of inflammatory bowel diseases - Crohn's disease and ulcerative colitis. Mounting evidence supports the concept of intricate relationship between gut dysbiosis and vitamin D metabolism, while suboptimal levels of this vitamin have been linked to increased clinical disease relapse rates, inadequate response to drugs, as well as decreased quality of life in patients with Crohn's disease and ulcerative colitis.

Antibacterial Activity of Polyoxometalates Against .

The antibacterial activity of 29 different polyoxometalates (POMs) against was investigated by determination of the minimum inhibitory concentration (MIC). The Preyssler type polyoxotungstate (POT) [NaPWO] demonstrates the highest activity against (MIC = 1 μg/ml) among all tested POMs. Moreover, we show that the Dawson type based anions, [PWO], [(PO)MoO], [AsMoO], [HPWVO], and [AsWO] are selective on (MIC range of 2-8 μg/ml).

Methodology challenges in studying human gut microbiota - effects of collection, storage, DNA extraction and next generation sequencing technologies.

The information on microbiota composition in the human gastrointestinal tract predominantly originates from the analyses of human faeces by application of next generation sequencing (NGS). However, the detected composition of the faecal bacterial community can be affected by various factors including experimental design and procedures. This study evaluated the performance of different protocols for collection and storage of faecal samples (native and OMNIgene.

Antibacterial and antiproliferative activity of novel 2-benzimidazolyl- and 2-benzothiazolyl-substituted benzo[b]thieno-2-carboxamides.

Novel nitro (3a-3f)- and amino (4a-4f and 5a-5f)-substituted 2-benzimidazolyl and 2-benzothiazolyl benzo[b]thieno-2-carboxamides were designed and synthesized as potential antibacterial agents. The antibacterial activity of these compounds has been evaluated against Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Moraxella catarrhalis). The most promising antibacterial activity was observed for the nitro- and amino-substituted benzimidazole derivatives 3a, 4a, 5a and 5b with MICs 2-8 [Formula: see text].

Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds.

Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens In Vitro and In Vivo.

As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds.

Synthesis and evaluation of antibacterial and antioxidant activity of novel 2-phenyl-quinoline analogs derivatized at position 4 with aromatically substituted 4H-1,2,4-triazoles.

A set of novel quinolone-triazole conjugates (12-31) were synthesized in three steps in good yields starting from 2-phenylquinoline-4-carboxylic acid. All the intermediates, as well as the final 1,2,4-triazolyl quinolines were fully characterized by their detailed spectral analysis utilizing different techniques such as IR, H NMR, C NMR, and finally mass spectrometry. All the synthesized compounds were evaluated in vitro for their potential antibacterial activity and their preliminary safety profile was assessed through cytotoxicity assay.

Modulating Composition and Metabolic Activity of the Gut Microbiota in IBD Patients.

The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce.

1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity.

Versatile 1,2,3-triazole pharmacophore-based benzofused heterocycles containing halogen-substituted aromatic (9-17 and 25-28), 7-substituted coumarin (18-23 and 29-30) or penciclovir-like subunit (31a,b-38a) were designed and synthesized to evaluate their antibacterial activities against selected Gram-positive and Gram-negative bacteria. Hybridization approach using environmentally friendly Cu(I)-catalyzed click reaction under microwave irradiation was adopted in the synthesis of regioselective 1,4-disubstituted 1,2,3-triazole tethered heterocycles (9-23 and 25-30), while post-N-alkylation of NH-1,2,3-triazoles afforded both 2,4- (31a-38a) and 1,4-disubstituted (31b-33b, 35b-37b) 1,2,3-triazole regioisomers. The compounds 18-23 and 25-30 revealed fluorescence in the violet region of the visible spectrum with a strong influence of phenyl spacer in 25-30 on both wavelength and emission intensity.

Synthesis and structure-activity relationship of amidine derivatives of 3,4-ethylenedioxythiophene as novel antibacterial agents.

Current antibacterial chemotherapeutics are facing an alarming increase in bacterial resistance pressuring the search for novel agents that would expand the available therapeutic arsenal against resistant bacterial pathogens. In line with these efforts, a series of 9 amidine derivatives of 3,4-ethylenedioxythiophene were synthesized and, together with 18 previously synthesized analogs, evaluated for their relative DNA binding affinity, in vitro antibacterial activities and preliminary in vitro safety profile. Encouraging antibacterial activity of several subclasses of tested amidine derivatives against Gram-positive (including resistant MRSA, MRSE, VRE strains) and Gram-negative bacterial strains was observed.

Macrolactonolides: a novel class of anti-inflammatory compounds.

A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats.

An efficient and convenient microwave-assisted chemical synthesis of (thio)xanthones with additional in vitro and in silico characterization.

Xanthones and their thio-derivatives are a class of pleiotropic compounds with various reported pharmacological and biological activities. Although these activities are mainly determined in laboratory conditions, the class itself has a great potential to be utilized as promising chemical scaffold for the synthesis of new drug candidates. One of the main obstacles in utilization of these compounds was related to the difficulties in their chemical synthesis.