Search Results (8)

Acidic amino acid peptides have a high affinity for bone. Previously, we demonstrated that radiogallium complex-conjugated oligo-acidic amino acids possess promising properties as bone-seeking radiopharmaceuticals. Here, to elucidate the effect of stereoisomers of Glu in Glu-containing peptides [(Glu)₁₄] on their accumulation in the kidney, the biodistributions of [⁶⁷Ga]Ga-N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid-conjugated (l-Glu)₁₄ ([⁶⁷Ga]Ga-HBED-CC-(l-Glu)₁₄), [⁶⁷Ga]Ga-HBED-CC-(d-Glu)₁₄, [⁶⁷Ga]Ga-HBED-CC-(dl-Glu)₁₄, and [⁶⁷Ga]Ga-HBED-CC-(d-Glu-l-Glu)₇ were compared. Although the accumulation of these compounds in the bone was comparable, their kidney accumulation and retention were strikingly different, with [⁶⁷Ga]Ga-HBED-CC-(d-Glu-l-Glu)₇ exhibiting the lowest level of kidney accumulation among these compounds. Repeated d- and l-peptides may be a useful method for reducing renal accumulation in some cases. Full article

Cellular iron supply is required for various biochemical processes. Measuring bioavailable iron in cells aids in obtaining a better understanding of its biochemical activities but is technically challenging. Existing techniques have several constraints that make precise localization difficult, and the lack of a functional readout makes it unclear whether the tested labile iron is available for metalloproteins. Here, we use geNOps; a ferrous iron-dependent genetically encoded fluorescent nitric oxide (NO) biosensor, to measure available iron in cellular locales. We exploited the nitrosylation-dependent fluorescence quenching of geNOps as a direct readout for cellular iron absorption, distribution, and availability. Our findings show that, in addition to ferrous iron salts, the complex of iron (III) with N,N’-bis (2-hydroxybenzyl)ethylenediamine-N,N’-diacetic acid (HBED) can activate the iron (II)-dependent NO probe within intact cells. Cell treatment for only 20 min with iron sucrose was also sufficient to activate the biosensor in the cytosol and mitochondria significantly; however, ferric carboxymaltose failed to functionalize the probe, even after 2 h of cell treatment. Our findings show that the geNOps approach detects available iron (II) in cultured cells and can be applied to assay functional iron (II) at the (sub)cellular level. Full article

The Knoevenagel reaction is an essential synthetic tool in the organic and medicinal chemistry of thiazolidin-4-one derivatives. In the present work, the application of ethylenediamine diacetate (EDDA) as an effective catalyst for the interaction of 2-thioxothiazolidin-4-one with 4-(tert-butyl)cyclohexanone is proposed. The structure of novel synthesized 5-[4-(tert-butyl)cyclohexylidene]-2-thioxothiazolidin-4-one (yield 61%) was confirmed by ¹H-, ¹³C-NMR, LC-MS, IR, and UV spectra. Drug-like properties of the synthesized compound were evaluated in silico using the SwissAdme, and their potential antimicrobial activity against 15 strains of Gram-positive and Gram-negative bacteria as well as yeasts was evaluated in vitro. The synthesized compound possesses satisfactory drug-like parameters and promising antimicrobial properties and presents interest as a prospective intermediate for the forthcoming design of biologically active small molecules. Full article

Two new aminodiphosphonic acids derived from salicylic acid and its phosphonic analogue were prepared through a simple and efficient synthesis. 2-[(2-Amino-2,2-diphosphono)ethyloxy]-benzoic acid 8 and 2-[(2-amino-2,2-diphosphono)ethyloxy]-5-ethyl-phenylphosphonic acid 9 were evaluated for their applicability as ⁶⁸Ga binding bone-seeking agents. Protonation constants of 8 and 9 and stability constants of the Ga³⁺ complexes with 8 and 9 in water were determined. The stability constant of Ga³⁺ complex with fully phosphorylated acid 9 (logK_GaL = 31.92 ± 0.32) significantly exceeds stability constant of Ga³⁺ complex with 8 (logK_GaL = 26.63 ± 0.24). Ligands 8 and 9 are as effective for Ga³⁺ cation binding as ethylenediamine-N,N’-diacetic-N,N’-bis(methy1enephosphonic) acid and ethylenediamine-N,N,N’,N’-tetrakis(methylenephosphonic) acid, respectively. The labelling process and stability of [⁶⁸Ga]Ga-8 and [⁶⁸Ga]Ga-9 were studied. Both 8 and 9 readily form ⁶⁸Ga-complexes stable to ten-fold dilution with saline. However, in fetal bovine serum, only [⁶⁸Ga]Ga-9 was stable enough to be subject to biological evaluation. It was injected into rats with bone pathology and aseptic inflammation of soft tissues. For [⁶⁸Ga]Ga-9 in animals with a bone pathology model in 60 and 120 min after injection, a slight accumulation in the pathology site, stable blood percentage level, and moderate accumulation in the liver were observed. For animals with an aseptic inflammation, the accumulation of [⁶⁸Ga]Ga-9 in the pathology site was higher than that in animals with bone pathology. Moreover, the accumulation of [⁶⁸Ga]Ga-9 in inflammation sites was more stable than that for [⁶⁸Ga]Ga-citrate. The percentage of [⁶⁸Ga]Ga-9 in the blood decreased from 3.1% ID/g (60 min) to 1.5% ID/g (120 min). Accumulation in the liver was comparable to that obtained for [⁶⁸Ga]Ga-citrate. Full article

Targeting the iron requirement of Pseudomonas aeruginosa may be an effective adjunctive for conventional antibiotic treatment against biofilm-dwelling P. aeruginosa. We, therefore, assessed the anti-biofilm activity of N,N’-bis (2-hydroxybenzyl) ethylenediamine-N,N’-diacetic acid (HBED), which is a synthetic hexadentate iron chelator. The effect of HBED was studied using short-term (microtitre plate) and longer-term (flow-cell) biofilm models, under aerobic, anaerobic, and microaerobic (flow-cell) conditions and in combination with the polymyxin antibiotic colistimethate sodium (colistin). HBED was assessed against strains of P. aeruginosa from patients with cystic fibrosis and the reference strain PAO1. HBED inhibited growth and biofilm formation of all clinical strains under aerobic and anaerobic conditions, but inhibitory effects against PAO1 were predominantly exerted under anaerobic conditions. PA605, which is a clinical strain with a robust biofilm-forming phenotype, was selected for flow-cell studies. HBED significantly reduced biomass and surface coverage of PA605, and, combined with colistin, HBED significantly enhanced the microcolony killing effects of colistin to result in almost complete removal of the biofilm. HBED combined with colistin is highly effective in vitro against biofilms formed by clinical strains of P. aeruginosa. Full article

This work deals with the degradation of phenol based on the classical Fenton process, which is enhanced by the presence of chelating agents. Several iron-chelating agents such as ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), diethylenetriamine pentaacetic acid (DTPA), and ethylenediamine-N,N’-diacetic acid (EDDA) were explored, although particular attention was given to EDTA. The effect of the molar ligand to iron ratio, EDTA:Fe, initial pH, and temperature on the oxidation process was studied. The results demonstrate that the proposed alternative approach allows the capacity for degrading phenol to be extended from the usual acidic pH (around 3.0) to circumneutral pH range (6.5–7.5). The overall feasibility of the process depends on the concentration of the chelating agent and the initial pH of the solution. The maximum phenol conversion, over 95%, is achieved using a 0.3 to 1 molar ratio of EDTA:Fe, stoichiometric ratio of H₂O₂ at an initial pH of 7.0, and a temperature of 30 °C after 2 hours of reaction, whereas only 10% of phenol conversion is obtained without EDTA. However, in excess of ligand (EDTA:Fe > 1), the generation of radicals seems to be strongly suppressed. Improvement of the phenol removal efficiency at neutral pH also occurs for the other chelating agents tested. Full article

The novel Gallium-68 prostate-specific membrane antigen (PSMA)-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-diacetic acid positron emission tomography (PET) tracer is increasingly used in the evaluation of prostate cancer, particularly in the detection of recurrent disease. However, PSMA is expressed in nonprostatic tissues, as well as in other pathologic conditions. Here we illustrate such interpretive pitfalls with relevant images that one may encounter while reporting PSMA PET/CT. This study aims to show variation in physiological distribution of PSMA activity and uptake in various benign and neoplastic disorders that may be misinterpreted as prostatic metastatic disease. These pitfalls are illustrated to enhance awareness, aiding a more accurate interpretation of the study. Retrospective database of all (68)Ga PSMA PET/CT was created and reviewed. In total, 1115 PSMA PET/CT studies performed between February 27, 2015, and May 31, 2017, were reviewed. Any unusual uptake of PSMA was documented, described, and followed up. All cases were then subdivided into the following 4 categories: physiological uptake, benign pathological uptake, nonprostatic neoplastic uptake, and miscellaneous uptake. A variety of nonprostatic tissues and lesions, including accessory salivary gland, celiac ganglion, gall bladder, Paget's bone disease, reactive lymph nodes, non–small cell lung cancer, renal cell cancer, and neuroendocrine tumor, were found to show PSMA uptake. PSMA uptake is not prostate-specific and can be taken up physiologically and pathologically in nonprostatic tissue. It is important for reporting physicians to recognize these findings and instigate appropriate investigations when required while avoiding unnecessary procedures in physiological variation. Full article