Molybdenum (Mo) is an essential element for human life, acting as a cofactor in various enzymes crucial for metabolic homeostasis. This review provides a comprehensive insight into the latest advances in research on molybdenum-containing enzymes and their clinical significance. One of these enzymes is xanthine oxidase (XO), which plays a pivotal role in purine catabolism, generating reactive oxygen species (ROS) capable of inducing oxidative stress and subsequent organ dysfunction. Elevated XO activity is associated with liver pathologies such as non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Aldehyde oxidases (AOs) are also molybdenum-containing enzymes that, similar to XO, participate in drug metabolism, with notable roles in the oxidation of various substrates. However, beneath its apparent efficacy, AOs’ inhibition may impact drug effectiveness and contribute to liver damage induced by hepatotoxins. Another notable molybdenum-enzyme is sulfite oxidase (SOX), which catalyzes the conversion of sulfite to sulfate, crucial for the degradation of sulfur-containing amino acids. Recent research highlights SOX’s potential as a diagnostic marker for HCC, offering promising sensitivity and specificity in distinguishing cancerous lesions. The newest member of molybdenum-containing enzymes is mitochondrial amidoxime-reducing component (mARC), involved in drug metabolism and detoxification reactions. Emerging evidence suggests its involvement in liver pathologies such as HCC and NAFLD, indicating its potential as a therapeutic target. Overall, understanding the roles of molybdenum-containing enzymes in human physiology and disease pathology is essential for advancing diagnostic and therapeutic strategies for various health conditions, particularly those related to liver dysfunction. Further research into the molecular mechanisms underlying these enzymes’ functions could lead to novel treatments and improved patient outcomes.
Transition metal catalysts play a prominent role in modern organic and polymer chemistry, enabling many transformations of academic and industrial significance. However, the use of organometallic catalysts often requires the removal of their residues from reaction products, which is particularly important in the pharmaceutical industry. Therefore, the development of efficient and economical methods for the removal of metal contamination is of critical importance. Herein, we demonstrate that commercially available 1,4-bis(3-isocyanopropyl)piperazine can be used as a highly efficient quenching agent (QA) and copper scavenger in Cu/TEMPO alcohol aerobic oxidation (Stahl oxidation) and atom transfer radical polymerization (ATRP). The addition of QA immediately terminates Cu-mediated reactions under various conditions, forming a copper complex that can be easily separated from both small molecules and macromolecules. The purification protocol for aldehydes is based on the addition of a small amount of silica gel followed by QA and filtration. The use of QA@SiO2 synthesized in situ results in products with Cu content usually below 5 ppm. Purification of polymers involves only the addition of QA in THF followed by filtration, leading to polymers with very low Cu content, even after ATRP with high catalyst loading. Furthermore, the addition of QA completely prevents oxidative alkyne–alkyne (Glaser) coupling. Although isocyanide QA shows moderate toxicity, it can be easily converted into a non-toxic compound by acid hydrolysis.
1 October 2016 in European Journal of Medicinal Chemistry
Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (Fe3O4) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody—trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy.
Identification and quantification of the selenium species in biological tissues is imperative, considering the need to properly understand its metabolism and its importance in various field of sciences, especially nutrition science. Although a number of studies deals with the speciation of selenium, speciation analysis is still far from being a routine task, and so far strongly depends on the type of the samples. We present a study aimed to examine speciation analysis of Se in tissues of livers, muscles, and hearts obtained from lambs, namely in liver, muscle, and heart. The studied lambs were fed with the diet enriched with an inorganic (as sodium selenate) and organic chemical form of Se (as Se-enriched yeast) compounds with simultaneous addition of fish oil (FO) and carnosic acid (CA). The first part of the work was focused on the optimization of the extraction procedure of selenium compounds from tissues. Next, hyphenated high performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC–ICP–MS) was used for the identification of five seleno-compounds—Se-methionine (SeMet), Se-cystine (SeCys2), Se-methyl-Se-cysteine (SeMetSeCys), and Se(IV) and Se(VI). Verification of the identified seleno-compounds was achieved using triple-quadrupole mass spectrometer coupled to high performance liquid chromatography (HPLC–ESI–MS/MS). The applied procedure allowed for quantitative analysis of SeMet, SeCys2, and SeMetSeCys, in biological tissues. The developed analytical protocol is feasible for speciation analysis of small molecular seleno-compounds in animals samples.