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Mesoporous silica nanoparticles, with and without the inclusion of a magnetic core, were hydrothermally synthesized and employed as carrier of the antibiotic norfloxacin (NFX). The antibiotic-loaded materials were prepared by wet impregnation. Differences in drug content (and in further release profile) were directly related to changes in surface area, particle aggregation and hydrophobicity of the solids. The kinetics of NFX release has been studied in batch experiments. In all cases, more than 55% of the antibiotic was quickly desorbed during the first 5 min due to the localization of NFX on the external surface of the nanoparticles. The rest of the drug (situated inside the mesopores) was released through a diffusion-controlled transport and the rate was strongly dependent of the pH, reaching its minimum value at neutral pH. The calculated activation energy confirmed that the release was controlled by a diffusion process. Breaking of H-bonds and electrostatic and hydrophobic interactions appear to be responsible for NFX desorption from the solid surface. Such interactions increase, however, the thermal stability of the drug when the NFX and the carriers are combined. The antimicrobial activities of the drug loaded nanoparticles and the free antibiotic were compared and discussed. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (PLGA micro-particles), containing a model antibacterial drug (vancomycin hydrochloride). In order to understand the key parameters ruling the performance of this delivery system, we developed a mathematical model able to discriminate the drug diffusion inside micro-particles and within the gel phase, eventually providing to predict the drug release kinetics. The model reliability was confirmed by fitting to experimental data, proposing as a powerful theoretical approach to design and optimize such in situ delivery systems. [ABSTRACT FROM AUTHOR]

Microbial infections still remain one of the main issues for human health. The rapid development of resistance towards the most common antimicrobial drugs in bacteria represents today a challenge in the infections management. In the present work we have investigated the antibacterial activity of a group of compounds, namely silver N -heterocyclic carbene complexes, against a broad spectrum of bacteria. For the most promising compound, a biopolymeric nanocarrier has been developed, in order to potentiate the metal complex activity against both Gram +ve and Gram −ve. The polymeric nanovehicle is based on dextran, modified with oleic acid residues, that confer amphiphilic properties to the polysaccharide. We have characterized the obtained biomaterial and studied its ability to self-assemble into nanoparticles in aqueous environment. Next, the transdermal diffusion analyses have been carried out to evaluate the ability of the polymeric particles to penetrate tissues. Thanks to the strategy adopted, we have fabricated an antibacterial system to which K. pneumoniae and E. coli are the most sensitive. [ABSTRACT FROM AUTHOR]

Preparation, characterization, and application of alkali starch (AS) given by dry co-grinding of starch and alkali is described in this work. Grinding using a mortar (agate) and pestle or, more conveniently, a ball mill has been found to be satisfactory for the preparation of the AS. The AS products were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) and x-ray fluorescence (XRF) analyses. The base capacities of ASs were 4.25–4.45 mmol/g, respectively. AS is a low cost and easy to handle base catalyst that showed promising catalytic performance in the synthesis of a dihydroquinazoline-based antibacterial drug that involves tandem hydration or decarboxylative amidation, imination, and Aza-Michael reactions. [ABSTRACT FROM AUTHOR]

Legionella pneumophila is an aerobic, Gram-negative bacterium of the genus Legionella , which constitutes the major causative agent of Legionnaires’ disease. Recently a nucleoside triphosphate diphosphohydrolase (NTPDase) from L. pneumophila was identified and termed Lp1NTPDase; it was found to be a structural and functional homolog of mammalian NTPDases catalyzing the hydrolysis of ATP to ADP and ADP to AMP. Its activity is believed to contribute to the virulence of Legionella pneumophila . Therefore Lp1NTPDase inhibitors are considered as novel antibacterial drugs. However, only weakly potent compounds are available so far. In the present study, a capillary electrophoresis (CE)-based enzyme assay for monitoring the Lp1NTPDase activity was established. The enzymatic reaction was performed in a test tube followed by separation of substrate and products by CE and subsequent quantification by UV analysis. After kinetic characterization of the enzyme, a series of 1-amino-4-ar(alk)ylamino-2-sulfoanthraquinone derivatives structurally related to the anthraquinone dye Reactive Blue 2, a non-selective ecto-NTPDase inhibitor, was investigated for inhibitory activity on Lp1NTPDase using the CE-based enzyme assay. Derivatives bearing a large lipophilic substituent (e.g., fused aromatic rings) in the 4-position of the 1-amino-2-sulfoanthraquinone showed the highest inhibitory activity. Compounds with IC 50 values in the low micromolar range were identified. The most potent inhibitor was 1-amino-4-[phenanthrene-9-yl-amino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate ( 28 , PSB-16131), with an IC 50 -value of 4.24 μM. It represents the most potent Lp1NTPDase inhibitor described to date. These findings may serve as a starting point for further optimization. Lp1NTPDase inhibition provides a novel approach for the (immuno)therapy of Legionella infections. [ABSTRACT FROM AUTHOR]

The docking approach for the screening of designed small molecule ligands, led to the identification of a critical arginine residue in peptide deformylase for spiro cyclopropyl PDF inhibitor’s extra hydrophobic binding, providing us a useful tool for searching more efficient PDF inhibitors to fight for horrifying antibiotics resistance. Further synthetic modification was undertaken to optimize the potency of amide compounds. To lower metabolic susceptibility and in turn reduce unwanted metabolic toxicity that was observed clinically, while retaining desired antibacterial activity, the use of azoles as amide bioisosteres had also been investigated. After the completion of chemical synthesis, all the compounds were evaluated through in vitro antibacterial activity assay, some of which were further subject to in vivo rat pharmacokinetic assessment. Those findings in this letter showed that spiro cyclopropyl proline N -formyl hydroxylamines, and especially the bioisosteric azoles, can represent a promising class of PDF inhibitors. [ABSTRACT FROM AUTHOR]

The occurrence of 41 pharmaceuticals and phytochemicals (PPs) including their metabolites was surveyed in hospital effluent in an urban area of Japan. A detailed survey of sewage treatment plant (STP) influent and effluent, and river water was also conducted. Finally, mass balances with mass fluxes of the target PPs through the water flow were evaluated and the degree of contribution of hospital effluent to the environmental discharge was estimated. The results indicate that 38 compounds were detectable in hospital effluent over a wide concentration range from ng/L to μg/L, with a maximum of 92 μg/L. The contributions of PPs in the hospital effluent to STP influent varied widely from < 0.1% to 14.8%. Although almost all of the remaining components could be removed below 1.0 ng/L at STPs by the addition of ozone treatment, a number of PPs still remained above 10 ng/L in STP effluent. These findings suggest the importance of applying highly developed treatments to hospital effluents and at STPs in the future to reduce the environmental risks posed by PPs. To our knowledge, this is the first demonstration of the presence of two conjugated metabolites of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate, as well as of loxoprofen and loxoprofen alcohol, in hospital effluent, STP, and river waters. [ABSTRACT FROM AUTHOR]

Abstract: We hypothesized that low-intensity focused ultrasound (LIFU) increases vessel permeability and antibacterial drug activity in the mouse middle ear. We determined appropriate settings by applying LIFU to mouse ears with the external auditory canal filled with normal saline and performed histologic and immunohistologic examination. Acute otitis media was induced in mice with nontypable Haemophilus influenzae, and they were given ampicillin (50, 10, or 2 mg/kg) intraperitoneally once daily for 3 days with or without LIFU (1.0 W/cm2, 20% duty cycle, 30 s). In the LIFU(+) groups receiving the 2- and 10-mg/kg doses, viable bacteria counts, number of inflammatory cells and IL-1β and TNF-α levels in middle ear effusion were significantly lower than in the LIFU(−) groups on the same doses. Severity of AOM also tended to be reduced more in the LIFU(+) groups than in the LIFU(−) groups. LIFU application with antibiotics may be effective for middle ear infection. [Copyright &y& Elsevier]

As a representative species of Lepidoptera, Bombyx mori has been widely studied and applied. However, bacterial infection has always been an important pathogen threatening the growth of silkworms. Bombyx mori can resist various pathogenic bacteria through their own physical barrier and innate immune system. However, compared with other insects, such as Drosophila melanogaster , research on the antibacterial mechanism of silkworms is still in its infancy. This review systematically summarized the routes of bacterial infection in silkworms, the antibacterial mechanism of silkworms after ingestion or wounding infection, and the intestinal bacteria and infection of silkworms. Finally, we will discuss silkworms as a model animal for studying bacterial infectious diseases and screening antibacterial drugs. • Route of bacterial infection in silkworms. • Molecular mechanism of bacterial infection in silkworms. • Silkworms as an animal model for studying bacterial infectious. • Silkworms as an animal model for screening for antibacterial drugs. [ABSTRACT FROM AUTHOR]

Abstract: From the reaction of 6-(p-methoxyphenyl) fulvene (1a), 6-(p-N,N-dimethylaminophenyl) fulvene (1b) and 6-(3,4-dimethoxyphenyl) fulvene (1c) with LiBEt3H, lithiated cyclopentadienide intermediates (2a–c) were synthesised. These intermediates were then transmetallated to tin with SnCl4 to yield tetra-substituted bis(cyclopentadienyl)tin dichloride complexes (3a–c). Further reaction with tin tetrachloride yielded the benzyl-substituted derivatives bis-[(p-methoxybenzyl)cyclopentadienyl] tin(IV) dichloride (4a), bis-[(p-N,N-dimethylaminobenzyl)cyclopentadienyl] tin(IV) dichloride (4b), and bis-[(3,4-dimethoxyphenyl)cyclopentadienyl] tin(IV) dichloride (4c). Preliminary antibacterial tests were carried out using the Kirby–Bauer disk-diffusion method, in which 4a–c showed little to no activity against the Gram-negative bacterium Escherichia coli, but medium activity against Gram-positive bacteria (MRSA, MSSA). In addition, the organotin complexes had their cytotoxicity investigated through preliminary in vitro testing on the LLC-PK (pig kidney epithelial) cell line in order to determine their IC50 values. Compound 4c showed no cytotoxic activity, while 4a and 4b were found to have IC50 values of 15 and 205μM, respectively. [Copyright &y& Elsevier]

Abstract: The suitability of micellar electrokinetic chromatography for the simultaneous trace determination of several compounds (sulfamethoxazole, trimethoprim, sulfanilic acid, sulfanilamide, 3,4,5-trimethoxybenzoic acid and nonoxynol-9) was assessed. The mixture was separated within 14min at an applied voltage of 22kV by using 30mM phosphate electrolyte, containing 10mM SDS, adjusted to pH 7.8. Under optimized separation conditions acceptable levels of linearity, precision and accuracy were obtained for all compounds. The method could be used as part of a cleaning validation study when assaying trace levels of co-trimoxazole drug, some of its decomposition products and detergent in the swab samples collected from pharmaceutical manufacturing equipment, after cleaning. [Copyright &y& Elsevier]

The enzyme 3-deoxy-d-manno-2-octulosonate-8-phosphate (KDO8P) synthase catalyzes the condensation reaction between phosphoenolpyruvate (PEP) and d-arabinose 5-phosphate (A5P) to produce KDO8P and inorganic phosphate. In attempts to investigate the lack of antibacterial activity of the most potent inhibitor of KDO8P synthase, the amino phosphonophosphate 3, we have synthesized its hydrolytically stable isosteric phosphonate analogue 4 and tested it as an inhibitor of the enzyme. The synthesis of 4 was accomplished in a one step procedure by employing the direct reductive amination in aqueous media between unprotected sugar phosphonate and glyphosate. The analogue 4 proved to be a competitive inhibitor of KDO8P synthase with respect to both substrates A5P and PEP binding. In vitro antibacterial tests against a series of different Gram-negative organisms establish that both inhibitors (3 and 4) lack antibacterial activity probably due to their reduced ability to penetrate the bacterial cell membrane. [Copyright &y& Elsevier]

The interaction of lumazine, an antibacterial drug, with α-, β-cyclodextrins and DNA in aqueous solution was studied by differential pulse stripping voltammetry and cyclic voltammetry as well as UV–vis spectroscopy. The electrochemical and absorption spectral data indicated a 1:1 complex formation of lumazine with α-, β-cyclodextrins and DNA. The nature of the process, taking place at the hanging mercury drop electrode, was clarified. It was found that the complexation of lumazine molecules enhances the stacking interactions which might facilitate the formation of a perpendicularly stacked layer of lumazine-α-cyclodextrin complex on the electrode surface. Based on the variations in the current or absorbance, the formation constants and consequently, the Gibbs energy of these complexes were determined. The small size cavity of α-cyclodextrin was found to have a greater affinity for lumazine than the β-cyclodextrin. Moreover, the interactions of lumazine-α-cyclodextrin or lumazine-β-cyclodextrin inclusion complex with DNA have been investigated by means of voltammetry. The results suggest that lumazine displayed high affinity for DNA and the inclusion complex decomposed when it binds to DNA. [Copyright &y& Elsevier]

The bacterial thiopeptide thiostrepton (TS) is used as a veterinary medicine to treat bacterial infections. TS is a protein translation inhibitor, essentially active against Gram-positive bacteria and some Gram-negative bacteria. In procaryotes, TS abrogates binding of GTPase elongation factors to the 70S ribosome, by altering the structure of rRNA-L11 protein complexes. TS exerts also antimalarial effects by disrupting protein synthesis in the apicoplast genome of Plasmodium falciparum. Interestingly, the drug targets both the infectious pathogen (bacteria or parasite) and host cell, by inducing endoplasmic reticulum stress-mediated autophagy which contributes to enhance the host cell defense. In addition, TS has been characterized as a potent chemical inhibitor of the oncogenic transcription factor FoxM1, frequently overexpressed in cancers or other diseases. The capacity of TS to crosslink FoxM1, and a few other proteins such as peroxiredoxin 3 (PRX3) and the 19S proteasome, contributes to the anticancer effects of the thiopeptide. The anticancer activities of TS evidenced using diverse tumor cell lines, in vivo models and drug combinations are reviewed here, together with the implicated targets and mechanisms. The difficulty to formulate TS is a drag on the pharmaceutical development of the natural product. However, the design of hemisynthetic analogues and the use of micellar drug delivery systems should facilitate a broader utilization of the compound in human and veterinary medicines. This review shed light on the many pharmacological properties of TS, with the objective to promote its use as a pharmacological tool and medicinal product. [Display omitted] • Thiostrepton (TS) is an antibacterial drug used in veterinary medicine. • TS primarily targets ribosomal RNA in bacteria, and in malaria parasites. • The 19S proteasome and peroxiredoxin 3 are additional targets of TS. • Inhibition of the transcription factor FoxM1 mainly drives the anticancer effects of TS. • TS is not water-soluble but micellar formulations and synthetic analogues have been developed. [ABSTRACT FROM AUTHOR]

The derivative of nitro groups containing antibacterial drug is very essential in present days for the urinary infections of human beings and animals, therefore, monitoring or controlling the usage of these drugs are more important one. In this work, amperometric detection of nitrofurantoin (NFT) antibacterial drug was demonstrated using a simple fabrication of functionalized carbon nanofibers and carbon black hybrid composite (f-CNF/CB). The f-CNF/CB composite was prepared by one-pot simple ultrasonication process. The f-CNF/CB composite was characterized by various microscopic and spectroscopic methods. The f-CNF/CB composite was fabricated on glassy carbon electrode (GCE) to step up rapid electron transfer process via electrode-electrolyte interface. Thus, the f-CNF/CB/GCE showed superior electrochemical performance towards NFT in physiological pH condition. Amperometric detection of NFT using f-CNF/CB/GCE exhibited a wide response range from 0.05 to 104.66 µM with a limit of detection and sensitivity of 16 nM and 15.25 μA µM−1 cm−2, respectively. Besides, the superior electrochemical performance of the f-CNF/CB hybrid composite could be further utilized for the fabrication of new-generation sensing devices and energy storage devices like batteries/capacitors. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Dequalinium (DQ) is used to treat local bacterial infections. • DQ primarily targets mitochondria, protein kinase C and certain potassium channels. • A dozen of DQ target proteins have been identified, linked to the diverse pharmacological applications. • DQ is a useful agent to facilitate liposome-based drug delivery. • The multitargeted action of the drug is underlined in this review. For more than 60 years dequalinium chloride (DQ) has been used as anti-infective drug, mainly to treat local infections. It is a standard drug to treat bacterial vaginosis and an active ingredient of sore-throat lozenges. As a lipophilic bis-quaternary ammonium molecule, the drug displays membrane effects and selectively targets mitochondria to deplete DNA and to block energy production in cells. But beyond its mitochondriotropic property, DQ can interfere with the correct functioning of diverse proteins. A dozen of DQ protein targets have been identified and their implication in the antibacterial, antiviral, antifungal, antiparasitic and anticancer properties of the drug is discussed here. The anticancer effects of DQ combine a mitochondrial action, a selective inhibition of kinases (PKC-α/β, Cdc7/Dbf4), and a modulation of Ca2+-activated K+ channels. At the bacterial level, DQ interacts with different multidrug transporters (QacR, AcrB, EmrE) and with the transcriptional regulator RamR. Other proteins implicated in the antiviral (MPER domain of gp41 HIV-1) and antiparasitic (chitinase A from Vibrio harveyi) activities have been identified. DQ also targets α -synuclein oligomers to restrict protofibrils formation implicated in some neurodegenerative disorders. In addition, DQ is a typical bolaamphiphile molecule, well suited to form liposomes and nanoparticules useful for drug entrapment and delivery (DQAsomes and others). Altogether, the review highlights the many pharmacological properties and therapeutic benefits of this old 'multi-talented' drug, which may be exploited further. Its multiple sites of actions in cells should be kept in mind when using DQ in experimental research. [ABSTRACT FROM AUTHOR]

Abstract: Simocyclinone D8 (SD8) is known to affect Gram-positive bacteria only. By testing SD8 against several clinical isolates, we showed that SD8 resulted very active against Gram-negative bacteria from clinical specimens, while it was shown inactive against laboratory strains. The activity against the former was in part due to enhanced drug entry. In addition, SD8 appears to share chromosome- and plasmid-mediated resistance mechanisms with fluoroquinolones. [Copyright &y& Elsevier]