Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs-Individually and in Combination.

Background/objectives: The importance of fixed-dose combinations (FDCs) for the treatment of hypertension is well established. However, from a stability perspective, FDCs present a challenge since the degradation of one active pharmaceutical ingredient (API) can be affected by the presence of another API. The aim of this study was to compare the degradation behaviors and evaluate the degradation kinetics of three antihypertensive drugs, perindopril tert-butylamine (PER), amlodipine besylate (AML), and indapamide (IND).

Electrochemical Performance of Niobium MXenes with Lanthanum.

MXenes are the newest class of two-dimensional nanomaterials characterized by large surface area, high conductivity, and hydrophilicity. To further improve their performance for use in energy storage devices, heteroatoms or functional groups can be inserted into the Mxenes' structure increasing their stability. This work proposes insertion of lanthanum atoms into niobium-MXene (Nb-MX/La) that was characterized in terms of morphogy, structure, and electrochemical behavior.

The Role of Ovalbumin in Manganese Homeostasis during Chick Embryogenesis: An EPR Spectroscopic Study.

Ovalbumin (OVA), a protein vital for chick embryo nutrition, hydration, and antimicrobial protection, together with other egg-white proteins, migrates to the amniotic fluid and is orally absorbed by the embryo during embryogenesis. Recently, it has been shown that for optimal eggshell quality, the hen diet can be supplemented with manganese. Although essential for embryonic development, manganese in excess causes neurotoxicity.

Spectroscopic Characterization of the Binding and Release of Hydrophilic, Hydrophobic and Amphiphilic Molecules from Ovalbumin Supramolecular Hydrogels.

Protein-based hydrogels have attracted growing attention for pharmaceutical and biomedical applications. Ovalbumin (OVA), the hen egg white albumin, possessing good foaming and gelling properties and being widely used in the food industry, has recently been indicated as a potential pharmaceutical vehicle. In this study, the binding and release properties of pure OVA hydrogels were investigated by electron paramagnetic resonance (EPR) spin labeling.

The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization.

This study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical (). The binding of to HSA was studied by electron paramagnetic resonance (EPR) spectroscopy and imaging. The EPR protocol was also implemented for the study of matrix degradation, and ligand diffusion rate, in two additional spin-labeled hydrogels, containing 5-doxylstearate and 3-carbamoyl-proxyl.

Analysis of Fixed-Dose Combination of Three Antihypertensive Drugs by a Green and Quality by Design Approach.

This paper presents the result of a combined employment of Analytical Quality-by-Design and Green Analytical Chemistry principles for the development of a robust high-performance liquid chromatography method for simultaneous determination of fixed-dose combination of three drugs, perindopril tert-butylamine, amlodipine besylate and indapamide. Optimum conditions were achieved on ZORBAX Eclipse XDB-C18 column (150 mm × 4.6 mm, 5 μm particle size), the mobile phase comprising acetonitrile and phosphate buffer (30 mM, pH 2.

Complexes of copper(II) with tetradentate S,O-ligands: Synthesis, characterization, DNA/albumin interactions, molecular docking simulations and antitumor activity.

Four new complexes of copper(II) with S,O-tetradentate ligands, derivatives of thiosalicylic acid, encompassing an ethylene-, propylene-, butylene- and pentylene- bridge, were synthesized and characterized by microanalysis, molecular conductance and infrared (IR) spectra. The structures were assumed based on the previously mentioned analyses and confirmed with the results of electron paramagnetic resonance (EPR) spectra. The reactivity of complexes towards L-methionine (L-Met), L-cysteine (L-Cys) and guanosine-5'-monophosphate (5'-GMP) was also examined.

Facile Synthesis of L-Cysteine Functionalized Graphene Quantum Dots as a Bioimaging and Photosensitive Agent.

Nowadays, a larger number of aggressive and corrosive chemical reagents as well as toxic solvents are used to achieve structural modification and cleaning of the final products. These lead to the production of residual, waste chemicals, which are often reactive, cancerogenic, and toxic to the environment. This study shows a new approach to the modification of graphene quantum dots (GQDs) using gamma irradiation where the usage of reagents was avoided.

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition.

Three new thiosemicarbazones (TSCs) - as triapine analogues bearing a redox-active phenolic moiety at the terminal nitrogen atom were prepared. Reactions of - with CuCl·2HO in anoxic methanol afforded three copper(II) complexes, namely, (), [ (), and (), in good yields. Solution speciation studies revealed that the metal-free ligands are stable as - at pH 7.

Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes: Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity.

A series of thiosemicarbazone-coumarin hybrids ( and ) has been synthesised in 12 steps and used for the preparation of mono- and dinuclear copper(II) complexes, namely (), (), () and (), isolated in hydrated or solvated forms. Both the organic hybrids and their copper(II) and dicopper(II) complexes were comprehensively characterised by analytical and spectroscopic techniques, i.e.

EPR Investigation of the Brain Redox Status and Blood-Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD.

Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells.

Thiosemicarbazones continue to attract the interest of researchers as potential anticancer drugs. For example, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, or triapine, is the most well-known representative of this class of compounds that has entered multiple phase I and II clinical trials. Two new triapine derivatives and were prepared by condensation reactions of 2-pyridinamidrazone and S-methylisothiosemicarbazidium chloride with 3--(-butyloxycarbonyl) amino-pyridine-2-carboxaldehyde, followed by a Boc-deprotection procedure.

New Water-Soluble Copper(II) Complexes with Morpholine-Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action.

Six morpholine-(iso)thiosemicarbazone hybrids HL-HL and their Cu(II) complexes with good-to-moderate solubility and stability in water were synthesized and characterized. Cu(II) complexes [Cu(L)Cl] (1-6) formed weak dimeric associates in the solid state, which did not remain intact in solution as evidenced by ESI-MS. The lead proligands and Cu(II) complexes displayed higher antiproliferative activity in cancer cells than triapine.

Coordination and redox interactions of β-lactam antibiotics with Cu in physiological settings and the impact on antibacterial activity.

An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu with eight β-lactam antibiotics using UV-Vis spectrophotometry, EPR spectroscopy, and electrochemical methods.

Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization.

Wedelactone (WL), a plant polyphenolic derivative of coumestan, represents a promising anti-cancer agent. The underlying mechanisms of its action are not fully understood and appear to involve interplay with copper ions. Herein, we examined coordination and redox interactions of WL with Cu in phosphate buffer (pH 7), and in two breast cancer cell lines.

Coordinate and redox interactions of epinephrine with ferric and ferrous iron at physiological pH.

Coordinate and redox interactions of epinephrine (Epi) with iron at physiological pH are essential for understanding two very different phenomena - the detrimental effects of chronic stress on the cardiovascular system and the cross-linking of catecholamine-rich biopolymers and frameworks. Here we show that Epi and Fe form stable high-spin complexes in the 1:1 or 3:1 stoichiometry, depending on the Epi/Fe concentration ratio (low or high). Oxygen atoms on the catechol ring represent the sites of coordinate bond formation within physiologically relevant bidentate 1:1 complex.

Changes of the peripheral blood mononuclear cells membrane fluidity from type 1 Gaucher disease patients: an electron paramagnetic resonance study.

Gaucher disease (GD) is a lysosomal storage disorder, caused by an impaired function of β-glucocerebrosidase, which results in accumulation of glucocerebroside in cells, and altered membrane ordering. Using electron paramagnetic resonance spin labeling, a statistically significant difference in the order parameter between the peripheral blood mononuclear cell membranes of GD patients and healthy controls was observed. Moreover, the results show that the introduction of the enzyme replacement therapy leads to the restoration of the physiological membrane fluidity.

Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine.

Toxic effects of unconjugated bilirubin (BR) in neonatal hyperbilirubinemia have been related to redox and/or coordinate interactions with Cu. However, the development and mechanisms of such interactions at physiological pH have not been resolved. This study shows that BR reduces Cu to Cu in 1:1 stoichiometry.

Maleimido-proxyl as an EPR spin label for the evaluation of conformational changes of albumin.

Albumin is the most abundant plasma protein and as such has been the subject of many studies using a variety of techniques. One of them, capable of monitoring the conformational changes and the binding capacity of proteins, is electron paramagnetic resonance spectroscopy (EPR) spin labeling. To date, albumin has been investigated using a number of different spin labels, mostly spin-labeled fatty acids (SLFAs).

Investigation of the Halogenate-Hydrogen Peroxide Reactions Using the Electron Paramagnetic Resonance Spin Trapping Technique.

The differences in the mechanism of the halogenate reactions with the same oxidizing/reducing agent, such as HO contribute to the better understanding of versatile halogen chemistry. The reaction between iodate, bromate, and chlorate with hydrogen peroxide in acidic medium at 60 °C is investigated by using the electron paramagnetic resonance (EPR) spin trapping technique. Essential differences in the chemistry of iodate, bromate, and chlorate in their reactions with hydrogen peroxide have been evidenced by finding different radicals as governing intermediates.

In vivo EPR pharmacokinetic evaluation of the redox status and the blood brain barrier permeability in the SOD1 ALS rat model.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1 ALS rat model in the presymptomatic (preALS) and symptomatic (ALS) stages of the disease were investigated by in vivo EPR spectroscopy using three aminoxyl radicals with different cell membrane and BBB permeabilities, Tempol, 3-carbamoyl proxyl (3CP), and 3-carboxy proxyl (3CxP).

Iron-sulfur cluster damage by the superoxide radical in neural tissues of the SOD1(G93A) ALS rat model.

Extensive clinical investigations, in hand with biochemical and biophysical research, have associated brain iron accumulation with the pathogenesis of the amyotrophic lateral sclerosis (ALS) disease. The origin of iron is still not identified, but it is proposed that it forms redox active complexes that can participate in the Fenton reaction generating the toxic hydroxyl radical. In this paper, the state of iron in the neural tissues isolated from SOD1(G93A) transgenic rats was investigated using low temperature EPR spectroscopy and is compared with that of nontransgenic (NTg) littermates.

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)](-) (M = Ru, Os) complexes to human serum albumin.

Overall binding affinity of sodium or indazolium cis/trans-[MCl4(1H-indazole)(NO)] (M = Ru, Os) complexes towards human serum albumin (HSA) and high molecular mass components of the blood serum was monitored by ultrafiltration. HSA was found to be mainly responsible for the binding of the studied ruthenium and osmium complexes. In other words, this protein can provide a depot for the compounds and can affect their biodistribution and transport processes.

Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity.

The protective constituents of silymarin, an extract from Silybum marianum fruits, have been extensively studied in terms of their antioxidant and hepatoprotective activities. Here, we explore the electron-donor properties of the major silymarin flavonolignans. Silybin (SB), silychristin (SCH), silydianin (SD) and their respective 2,3-dehydroderivatives (DHSB, DHSCH and DHSD) were oxidized electrochemically and their antiradical/antioxidant properties were investigated.