UV-Cured Antibacterial Hydrogels Based on PEG and Monodisperse Heterofunctional Bis-MPA Dendrimers

Bacterial infections are one of the major threats to human health due to the raising crisis of antibiotic resistance. Herein, second generation antibacterial heterofunctional dendrimers based on 2,2-bis(methylol)propionic acid were synthesized. The dendrimers possessed six alkenes and 12 ammonium end-groups per molecule and were used to fabricate antibacterial hydrogels together with dithiol-functional polyethylene glycol (mol wt of 2, 6 and 10 kDa) as crosslinkers via thiol-ene chemistry. The network formation can be completed within 10 s upon UV-irradiation as determined by the stabilization of the storage modulus in a rheometer. The hydrogels swelled in aqueous media and could be functionalized with the N-hydroxysuccinimide ester of the dye disperse red 13, which allowed for visually studying the degradation of the hydrogels through the hydrolysis of the ester bonds of the dendritic component. The maximum swelling ratio of the gels was recorded within 4–8 h and the swelling ratios increased with higher molecular weight of the polyethylene glycol crosslinker. The gel formed with 10 kDa polyethylene glycol crosslinker showed the highest swelling ratio of 40 and good mechanical properties, with a storage modulus of 8 kPa. In addition, the hydrogels exhibited good biocompatibility towards both human fibroblasts and mouse monocytes, while showing strong antibacterial activity against both gram-positive and gram-negative bacteria.

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Polyethylene Glycol Pulsed Electrodeposition for the Development of Antifouling Coatings on Titanium

Coatings ◽

10.3390/coatings10050456 ◽

2020 ◽

Vol 10 (5) ◽

pp. 456 ◽

Cited By ~ 2

Author(s):

Judit Buxadera-Palomero ◽

Kim Albó ◽

Francisco Javier Gil ◽

Carlos Mas-Moruno ◽

Daniel Rodríguez

Keyword(s):

Polyethylene Glycol ◽

Human Fibroblast ◽

Bacterial Infections ◽

Soft Tissues ◽

Ion Beam ◽

Human Fibroblasts ◽

Physicochemical Characterization ◽

E Coli ◽

Fibroblast Adhesion ◽

Pulsed Electrodeposition

Titanium dental implants are widely used for the replacement of damaged teeth. However, bacterial infections at the interface between soft tissues and the implant can impair the functionality of the device and lead to failure. In this work, the preparation of an antifouling coating of polyethylene glycol (PEG) on titanium by pulsed electrodeposition was investigated in order to reduce Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) adhesion while maintaining human fibroblast adhesion. Different pulsed conditions were prepared and characterized by contact angle, Focused Ion Beam (FIB), Fourier Transformed Infrared Spectroscopy in the Attenuated Total Reflectance mode (ATR-FTIR), and X-ray photoelectron spectroscopy (XPS). XPS tested fibronectin adsorption. S. aureus, E. coli and human fibroblast adhesion was tested in vitro in both mono and co-culture settings. Physicochemical characterization proved useful for confirming the presence of PEG and evaluating the efficiency of the coating methods. Fibronectin adsorption decreased for all of the conditions, but an adsorption of 20% when compared to titanium was maintained, which supported fibroblast adhesion on the surfaces. In contrast, S. aureus and E. coli attachment on coated surfaces decreased up to 90% vs. control titanium. Co-culture studies with the two bacterial strains and human fibroblasts showed the efficacy of the coatings to allow for eukaryotic cell adhesion, even in the presence of pre-adhered bacteria.

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Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666191223110518 ◽

2020 ◽

Vol 20 (3) ◽

pp. 192-208 ◽

Cited By ~ 1

Author(s):

Talita Odriane Custodio Leite ◽

Juliana Silva Novais ◽

Beatriz Lima Cosenza de Carvalho ◽

Vitor Francisco Ferreira ◽

Leonardo Alves Miceli ◽

...

Keyword(s):

In Silico ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Mass Spectrometry Analysis ◽

World Health ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Dione Derivative ◽

In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

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Elucidating the Molecular Mechanisms for the Interaction of Water with Polyethylene Glycol-Based Hydrogels: Influence of Ionic Strength and Gel Network Structure

Polymers ◽

10.3390/polym13060845 ◽

2021 ◽

Vol 13 (6) ◽

pp. 845

Author(s):

Xin Yang ◽

Bronwin Dargaville ◽

Dietmar Hutmacher

Keyword(s):

Polyethylene Glycol ◽

Ionic Strength ◽

Molecular Mechanisms ◽

Repeat Unit ◽

Bound Water ◽

Weight Fraction ◽

Swelling Ratio ◽

Polyethylene Glycol Diacrylate ◽

Glycol Diacrylate ◽

Hydrogel System

The interaction of water within synthetic and natural hydrogel systems is of fundamental importance in biomaterial science. A systematic study is presented on the swelling behavior and states of water for a polyethylene glycol-diacrylate (PEGDA)-based model neutral hydrogel system that goes beyond previous studies reported in the literature. Hydrogels with different network structures are crosslinked and swollen in different combinations of water and phosphate-buffered saline (PBS). Network variables, polyethylene glycol (PEG) molecular weight (MW), and weight fraction are positively correlated with swelling ratio, while “non-freezable bound water” content decreases with PEG MW. The presence of ions has the greatest influence on equilibrium water and “freezable” and “non-freezable” water, with all hydrogel formulations showing a decreased swelling ratio and increased bound water as ionic strength increases. Similarly, the number of “non-freezable bound water” molecules, calculated from DSC data, is greatest—up to six molecules per PEG repeat unit—for gels swollen in PBS. Fundamentally, the balance of osmotic pressure and non-covalent bonding is a major factor within the molecular structure of the hydrogel system. The proposed model explains the dynamic interaction of water within hydrogels in an osmotic environment. This study will point toward a better understanding of the molecular nature of the water interface in hydrogels.

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The antimicrobial potential of cannabidiol

Communications Biology ◽

10.1038/s42003-020-01530-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Mark A. T. Blaskovich ◽

Angela M. Kavanagh ◽

Alysha G. Elliott ◽

Bing Zhang ◽

Soumya Ramu ◽

...

Keyword(s):

Bacterial Infections ◽

Modern Medicine ◽

Gram Negative Bacteria ◽

Gram Negative ◽

New Class ◽

Clostridioides Difficile ◽

Excellent Activity ◽

Induce Resistance ◽

First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

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Ceric ammonium nitrate (CAN) catalysed expeditious one-pot synthesis of 1,3-thiazine as IspE kinase inhibitor of Gram-negative bacteria using polyethylene glycol (PEG-400) as an efficient recyclable reaction medium

Comptes Rendus Chimie ◽

10.1016/j.crci.2012.11.019 ◽

2013 ◽

Vol 16 (5) ◽

pp. 462-468 ◽

Cited By ~ 4

Author(s):

Udaya Pratap Singh ◽

Hans Raj Bhat ◽

Ramendra Kumar Singh

Keyword(s):

Polyethylene Glycol ◽

Ammonium Nitrate ◽

Kinase Inhibitor ◽

Reaction Medium ◽

Ceric Ammonium Nitrate ◽

Gram Negative Bacteria ◽

One Pot ◽

Gram Negative ◽

Peg 400 ◽

One Pot Synthesis

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EFFECT OF THE HEXANIC EXTRACT OF TAGETES LUCIDA ON THE INHIBITION OF THE GROWTH OF ENTEROBACTERIA SHIGELLA FLEXNERI AND SALMONELLA TYPHI

Anales de la Real Academia Nacional de Farmacia ◽

10.53519/analesranf.2020.86.02.02 ◽

2020 ◽

pp. 113-116

Author(s):

Jorge Ángel Almeida-Villegas ◽

Rodolfo García-Contreras ◽

Miriam Deyanira Rodríguez ◽

Yahira Katherine Porras-Hernández ◽

Meliksetyan Lilit Surenovna ◽

...

Keyword(s):

Bacterial Infections ◽

Shigella Flexneri ◽

Salmonella Typhi ◽

Hexane Extract ◽

Gram Negative Bacteria ◽

Active Metabolites ◽

Inhibition Of Growth ◽

Total Inhibition ◽

Medicinal Plant Extracts ◽

New Strategies

Antibiotic resistance increases the search for new strategies to combat the diseases they cause, and the use of medicinal plants represents a highly effective and valuable strategy, such as the use of Tagetes lucida with different gram positive and gram negative bacteria. Objective: To evaluate the biological activity of the hexane extract of the Tagetes lucida plant at different concentrations on the inhibition of growth in plaque and tube of two enterobacteriaceae, Shigella flexneri and Salmonella typhi Methods: In the following work, a hexane extract from Tagetes lucida was evaluated on the growth inhibition of two enterobacteriaceae, Shigella flexneri and Salmonella typhi using different concentrations of vehicle to evaluate if it affected bacterial growth and also different concentrations of extract to evaluate activity. Results: Once the studies were carried out in triplicate, it was possible to specify that from 75µl/µg of extract, almost total inhibition of the growth of both bacteria was achieved, both in the plate method and in the tube method. And from 100 µl/µg total inhibition is achieved. Conclusions: The favorable results obtained with 75 µl/ µg, confirm that medicinal plant extracts are an important strategy to combat multi-drug resistant bacterial infections. On the other hand, it allows a study to be carried out to evaluate the most active metabolites of the extract, as well as the mechanism of action on the inhibition of the growth of the bacteria under study.

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An overview of carbapenem, its resistance and therapeutic options for infections caused by carbapenem resistant bacteria

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20203635 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1454

Author(s):

Hari P. Nepal ◽

Rama Paudel

Keyword(s):

Bacterial Infections ◽

Carbapenem Resistance ◽

Therapeutic Options ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Beta Lactam ◽

Gram Negative ◽

Penicillin Binding Proteins ◽

Carbapenem Resistant ◽

The World

Carbapenems are beta-lactam drugs that have broadest spectrum of activity. They are commonly used as the drugs of last resort to treat complicated bacterial infections. They bind to penicillin binding proteins (PBPs) and inhibit cell wall synthesis in bacteria. Important members that are in clinical use include doripenem, ertapenem, imipenem, and meropenem. Unlike other members, imipenem is hydrolyzed significantly by renal dehydropeptidase; therefore, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin. Carbapenems are usually administered intravenously due to their low oral bioavailability. Most common side effects of these drugs include nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Increasing resistance to these antibiotics is being reported throughout the world and is posing a threat to public health. Primary mechanisms of carbapenem resistance include expulsion of drug and inactivation of the drug by production of carbapenemases which may not only hydrolyze carbapenem, but also cephalosporin, penicillin, and aztreonam. Resistance especially among Gram negative bacteria is of much concern since there are only limited therapeutic options available for infections caused by carbapenem resistant Gram-negative bacterial pathogens. Commonly used drugs to treat such infections include polymyxins, fosfomycin and tigecycline.

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Anionic amino acids support hydrolysis of poly-β-(1,6)-N-acetylglucosamine exopolysaccharides by the biofilm dispersing glycosidase Dispersin B

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.015524 ◽

2020 ◽

pp. jbc.RA120.015524

Author(s):

Alexandra P Breslawec ◽

Shaochi Wang ◽

Crystal Li ◽

Myles B Poulin

Keyword(s):

Amino Acids ◽

Bacterial Infections ◽

Substrate Recognition ◽

Site Directed Mutagenesis ◽

Binding Surface ◽

Activity Measurements ◽

Rate Of Hydrolysis ◽

Biofilm Dispersal ◽

Hydrolysis Of

The exopolysaccharide poly-β-(1→6)-N-acetylglucosamine (PNAG) is a major structural determinant of bacterial biofilms responsible for persistent and nosocomial infections. The enzymatic dispersal of biofilms by PNAG-hydrolyzing glycosidase enzymes, such as Dispersin B (DspB), is a possible approach to treat biofilm dependent bacterial infections. The cationic charge resulting from partial de-N-acetylation of native PNAG is critical for PNAG-dependent biofilm formation. We recently demonstrated that DspB has increased catalytic activity on de-N-acetylated PNAG oligosaccharides, but the molecular basis for this increased activity is not known. Here, we analyze the role of anionic amino acids surrounding the catalytic pocket of DspB in PNAG substrate recognition and hydrolysis using a combination of site directed mutagenesis, activity measurements using synthetic PNAG oligosaccharide analogs, and in vitro biofilm dispersal assays. The results of these studies support a model in which bound PNAG is weakly associated with a shallow anionic groove on the DspB protein surface with recognition driven by interactions with the –1 GlcNAc residue in the catalytic pocket. An increased rate of hydrolysis for cationic PNAG was driven, in part, by interaction with D147 on the anionic surface. Moreover, we identified that a DspB mutant with improved hydrolysis of fully acetylated PNAG oligosaccharides correlates with improved in vitro dispersal of PNAG dependent Staphylococcus epidermidis biofilms. These results provide insight into the mechanism of substrate recognition by DspB and suggest a method to improve DspB biofilm dispersal activity by mutation of the amino acids within the anionic binding surface.

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Morpholine- and Thiomorpholine-Based Amidodithiophosphonato Nickel Complexes: Synthesis, Characterization, P–N Cleavage, Antibacterial Activity and Silica Nano-Dispersion

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.19058 ◽

2021 ◽

Vol 21 (5) ◽

pp. 2879-2891

Author(s):

Enrico Podda ◽

M. Carla Aragoni ◽

Massimiliano Arca ◽

Giulia Atzeni ◽

Simon J. Coles ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Activity ◽

Antibacterial Activity ◽

Nickel Complex ◽

Nickel Complexes ◽

Silica Matrix ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Ft Ir ◽

Hydrolysis Of

The reactivity of thiomorpholinium P-(4-methoxyphenyl)-N-thiomorpholin-amidodithiophosphonate (S-MorH+2)(S-Mor-adtp−) and morpholinium P-(4-methoxyphenyl)-N-morpholin-amidodithiophosphonate (O-MorH+2)(O-Mor-adtp−) towards nickel (II) dichloride hexahydrated is presented and the hydrolysis of the relevant metal complexes investigated. The hydrolytic products (S-MorH+2)2 [Ni(dtp)2]2− and (O-MorH+2)2[Ni(dtp)2]2− were characterized by means of FT-IR, 1H, and 31P NMR and XRD and the experimented P–N cleavage investigated and elucidated by means of DFT calculations. The antimicrobial activity of the neutral nickel complex [Ni(S-Mor-adtp)2] was tested against a set of Gram-positive and Gram-negative bacteria alongside with its nanodispersion in a silica matrix. The complex [Ni(S-Mor-adtp)2] did not show antibacterial activity, whilst the nano-dispersed sample [Ni(S-Mor-adtp)2]_SiO2 demonstrated inhibition to growth of Staphylococcus aureus. The nanocomposites were fully characterized by means of XRPD, TGA, SEM and dinitrogen sorption techniques.

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