The Efficacy of an N-Acetylcysteine-Antibiotic Combination Therapy on in a Cystic Fibrosis Sputum/Lung Cell Model.

Cystic fibrosis (CF) is a disorder causing dysfunctional ion transport resulting in the accumulation of viscous mucus. This environment fosters a chronic bacterial biofilm-associated infection in the airways. , a gram-negative aerobic bacillus, has been increasingly associated with antibiotic resistance and chronic colonisation in CF.

Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Quinolone Signaling System.

Quorum-sensing (QS) systems of  are involved in the control of biofilm formation and virulence factor production. The current study evaluated the ability of halogenated and a non-halogenated version (4d) to inhibit the QS receptor proteins LasR and PqsR. The DHP molecules exhibited concentration-dependent inhibition of LasR and PqsR receptor proteins.

Effect of -Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance.

Cystic fibrosis (CF) is a genetic disorder causing dysfunctional ion transport resulting in accumulation of viscous mucus that fosters chronic bacterial biofilm-associated infection in the airways. and are increasingly prevalent CF pathogens and while is slowly decreasing; all are complicated by multidrug resistance that is enhanced by biofilm formation. This study investigates potential synergy between the antibiotics ciprofloxacin (0.

N-Acetylcysteine Protects Bladder Epithelial Cells from Bacterial Invasion and Displays Antibiofilm Activity against Urinary Tract Bacterial Pathogens.

Urinary tract infections (UTIs) affect more than 150 million individuals annually. A strong correlation exists between bladder epithelia invasion by uropathogenic bacteria and patients with recurrent UTIs. Intracellular bacteria often recolonise epithelial cells post-antibiotic treatment.

Disruption of biofilms and killing of Burkholderia cenocepacia from cystic fibrosis lung using an antioxidant-antibiotic combination therapy.

Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The resulting chloride and bicarbonate imbalance produces a thick, static lung mucus. This mucus is not easily expelled from the lung and can be colonised by bacteria, leading to biofilm formation.

Covalent Immobilization of -Acetylcysteine on a Polyvinyl Chloride Substrate Prevents Bacterial Adhesion and Biofilm Formation.

Biofilm formation and antimicrobial resistance at surgical implant sites result in high morbidity and mortality. Identifying novel molecules that inhibit biofilm formation to coat surgical biomaterials is essential. One such compound is -acetylcysteine (NAC), a potent antioxidant precursor for glutathione, necessary in mammalian cells and known to disrupt/prevent biofilms.

The effect of N-acetylcysteine in a combined antibiofilm treatment against antibiotic-resistant Staphylococcus aureus.

Background: The WHO declared Staphylococcus aureus as a 'pathogen of high importance' in 2017. One-fifth of all bloodstream-related infections in Australia and 12 000 cases of bacteraemia in the UK (2017-18) were caused by the MRSA variant. To address the need for novel therapies, we investigated several permutations of an innovative combination therapy containing N-acetylcysteine (NAC), an antibiotic and an enzyme of choice in eradicating MRSA and MSSA biofilms.

Conditions Under Which Glutathione Disrupts the Biofilms and Improves Antibiotic Efficacy of Both ESKAPE and Non-ESKAPE Species.

Bacterial antibiotic resistance has increased in recent decades, raising concerns in hospital and community settings. Novel, innovative strategies are needed to eradicate bacteria, particularly within biofilms, and diminish the likelihood of recurrence. In this study, we investigated whether glutathione (GSH) can act as a biofilm disruptor, and enhance antibiotic effectiveness against various bacterial pathogens.

Application of the Morita-Baylis-Hillman reaction in the synthesis of 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones as potential HIV-1 integrase inhibitors.

A practicable six-step synthetic pathway has been developed to access a library of novel 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones using Morita-Baylis-Hillman methodology. These compounds and their 3-[(N-cycloalkylamino)methyl]-2-quinolone precursors have been screened as potential HIV-1 integrase (IN) inhibitors. A concomitant survey of their activity against HIV-1 protease and reverse-transcriptase reveals selective inhibition of HIV-1 IN.

Directed Growth of Orthorhombic Crystals in a Micropillar Array.

We report directed growth of orthorhombic crystals of potassium permanganate in spatial confinement of a micropillar array. The solution is introduced by spontaneous wicking to give a well-defined film (thickness 10-15 μm; volume ∼600 nL) and is connected to a reservoir (several microliters) that continuously "feeds" the evaporating film. When the film is supersaturated, crystals nucleate and preferentially grow in specific directions guided by one of several possible linear paths through the pillar lattice.

Influence of Sample Volume and Solvent Evaporation on Absorbance Spectroscopy in a Microfluidic "Pillar-Cuvette".

Spectroscopic analysis of solutions containing samples at high concentrations or molar absorptivity can present practical challenges. In absorbance spectroscopy, short optical path lengths or multiple dilution is required to bring the measured absorbance into the range of the Beer's Law calibration. We have previously reported an open "pillar-cuvette" with a micropillar array that is spontaneously filled with a precise (nL or μL) volume to create the well-defined optical path of, for example, 10 to 20 μm.

Pillar cuvettes: capillary-filled, microliter quartz cuvettes with microscale path lengths for optical spectroscopy.

The goal of most analytical techniques is to reduce the lower limit of detection; however, it is sometimes necessary to do the opposite. High sample concentrations or samples with high molar absorptivity (e.g.

Heteroditopic P,N ligands in gold(I) complexes: synthesis, structure and cytotoxicity.

New heteroditopic, bi- and multidentate imino- and aminophosphine ligands were synthesised and complexed to [AuCl(THT)] (THT=tetrahydrothiophene). X-ray crystallography confirmed Schiff base formation in three products, the successful reduction of the imino-group to the sp(3)-hybridised amine in several instances, and confirmed the formation of mono-gold(I) imino- and aminophosphine complexes for four Au-complexes. Cytotoxicity studies in cancerous and non-cancerous cell lines showed a marked increase in cytotoxicity upon ligand complexation to gold(I).

4-(3-Azaniumylpropyl)morpholin-4-ium chloride hydrogen oxalate: an unusual example of a dication with different counter-anions.

The mixed organic-inorganic title salt, C7H18N2O(2+)·C2HO4(-)·Cl(-), forms an assembly of ionic components which are stabilized through a series of hydrogen bonds and charge-assisted intermolecular interactions. The title assembly crystallizes in the monoclinic C2/c space group with Z = 8. The asymmetric unit consists of a 4-(3-azaniumylpropyl)morpholin-4-ium dication, a hydrogen oxalate counter-anion and an inorganic chloride counter-anion.

The evaluation of statins as potential inhibitors of the LEDGF/p75-HIV-1 integrase interaction.

Lovastatin was identified through virtual screening as a potential inhibitor of the LEDGF/p75-HIV-1 integrase interaction. In an AlphaScreen assay, lovastatin inhibited the purified recombinant protein-protein interaction (IC50 = 1.97 ± 0.

Gold-phosphine binding to de novo designed coiled coil peptides.

The coordination of the therapeutically interesting [AuCl(PEt(3))] to the de novo designed peptide, TRIL23C, under aqueous conditions, is reported here. TRIL23C represents an ideal model to investigate the binding of [AuCl(PEt(3))] to small proteins in an effort to develop novel gold(I) phosphine peptide adducts capable of mimicking biological recognition and targeting. This is due to the small size of TRIL23C (30 amino acids), yet stable secondary and tertiary fold, symmetric nature and the availability of only one thiol binding site.

Chlorido{N-[2-(diphenyl-phosphan-yl)benz-yl]-1-(pyridin-2-yl)methanamine-κP}gold(I).

In the title compound, [AuCl(C(25)H(23)N(2)P)], the Au(I) atom is in a typical almost linear coordination environment defined by phosphane P and Cl atoms [bond angle = 175.48 (4)°]. Helical supra-molecular chains along the b axis and mediated by N-H⋯Cl hydrogen bonds feature in the crystal packing.

{μ-1,2-Bis[bis(4-meth-oxy-phen-yl)phosphan-yl]-1,2-dimethyl-hydrazine-κP:P'}bis-[chloridogold(I)] tetra-hydro-furan disolvate.

The title compound, [Au(2)Cl(2)(C(30)H(34)N(2)O(4)P(2))]·2C(4)H(8)O, is formed from a bidentate phosphine ligand complexed to two almost linearly coordinated gold(I) atoms [P-Au-Cl = 175.68 (3) Å]. The nuclei are 3.

{μ-1,2-Bis[bis-(4-meth-oxy-phen-yl)phosphan-yl]-1,2-diethyl-hydrazine-κP:P'}bis-[chloridogold(I)] tetra-hydro-furan disolvate.

The title compound, [Au(2)Cl(2)(C(32)H(38)N(2)O(4)P(2))]·2C(4)H(8)O, is formed from a bidentate phosphine ligand complexed to two linear gold(I) nuclei [P-Au-Cl = 175.98 (3)°]. The nuclei are 3.

[μ-1,2-Bis(diphenyl-phosphan-yl)-1,2-diethyl-hydrazine-κP:P']bis-[chlorido-gold(I)] tetra-hydro-furan disolvate.

The title compound, [Au(2)Cl(2)(C(28)H(30)N(2)P(2))]·2C(4)H(8)O, was synthesized from a bidentate phosphine ligand complexed to two linear gold(I) chloride moieties. The Au(I) atom is in an almost linear coordination with a P-Au-Cl angle of 179.22 (4)°.

Dictyostatin flexibility bridges conformations in solution and in the β-tubulin taxane binding site.

Dictyostatin (DCT, 1) is a complex, flexible polyketide macrolide that demonstrates potent microtubule-polymerization activity. Both a solution structure (2a) and a possible binding mode for DCT (Conf-1) have been proposed by earlier NMR experiments. In the present study, the conformational landscape of DCT in DMSO-d(6) and methanol-d(4) was explored using extensive force-field-based conformational searches combined with geometric parameters derived from solution NMR data.

1,2-Bis(diphenyl-phosphino)-1,2-diethyl-hydrazine.

The title compound, C(28)H(30)N(2)P(2), adopts a well documented and studied gauche conformation around the hydrazine bond. Bond lengths and angles are in the typical ranges expected for P-N and P-C bonds. A normal hydrazine N-N bond length of 1.

Poly[[μ(2)-1,2-bis-(diphenyl-phosphan-yl)-1,2-diethylhydrazine]-μ(4)-nitrato-μ(2)-nitrato-silver(I)].

The title compound, [Ag(2)(NO(3))(2)(C(28)H(30)N(2)P(2))](n), crystallizes in polymeric α-helices. Three O atoms from three different nitrate ions in equatorial positions and two Ag atoms at axial positions set up a trigonal bipyramid. These units are linked by the phosphine ligands into endless helical chains that run along the c axis.

μ-1,2-Bis(diphenyl-phosphan-yl)-1,2-dimethyl-hydrazine-κP:P']bis-[chlorido-gold(I).

The title compound, [Au(2)Cl(2)(C(26)H(26)N(2)P(2))], is formed from a bidentate phosphine ligand complexed to two linearly coordinated gold(I) atoms. The gold(I) atoms are 3.4873 (7) Å apart.