Preparation of Diosgenin-Functionalized Gold Nanoparticles: From Synthesis to Antitumor Activities.

Cancer ranks among the top causes of illness and death globally. Nanotechnology holds considerable promise for enhancing the effectiveness of therapeutic and diagnostic approaches in cancer treatment. Our study presents a promising strategy for applying thiocompound nanomedicine in cancer therapy.

Salidroside: A Promising Agent in Bone Metabolism Modulation.

, a long-lived herbaceous plant from the Crassulaceae group, contains the active compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key regulatory proteins including runt-related transcription factor 2 and osterix.

Pyrrolizidine Alkaloids as Hazardous Toxins in Natural Products: Current Analytical Methods and Latest Legal Regulations.

Pyrrolizidine alkaloids (PAs) are toxic compounds that occur naturally in certain plants, however, there are many secondary pathways causing PA contamination of other plants, including medicinal herbs and plant-based food products, which pose a risk of human intoxication. It is proven that chronic exposure to PAs causes serious adverse health consequences resulting from their cytotoxicity and genotoxicity. This review briefly presents PA occurrence, structures, chemistry, and toxicity, as well as a set of analytical methods.

Development and Validation of LC-MS/MS Method for the Determination of 1-Methyl-4-Nitrosopiperazine (MNP) in Multicomponent Products with Rifampicin-Analytical Challenges and Degradation Studies.

Rifampicin is an essential medicine for treating and preventing tuberculosis (TB). TB is a life-threatening infectious disease and its prevention and treatment are public health imperatives. In the time of a global crisis of nitrosamine contamination of medicinal products, patient safety and a reduction in the number of drug recalls at the same time are crucial.

Computational Modeling of Gold Nanoparticle Interacting with Molecules of Pharmaceutical Interest in Water.

We derived a theory of biomolecule binding to the surface of Au clusters and of the Au plane based on the hard soft acid base (HSAB) principle and the free electron metallic surface model. With the use of quantum mechanical calculations, the chemical potential () and the chemical hardness () of the biomolecules are estimated. The effect of the gold is introduced via the empirical value of the gold chemical potential (-5.

Development of a Sensitive Screening Method for Simultaneous Determination of Nine Genotoxic Nitrosamines in Active Pharmaceutical Ingredients by GC-MS.

A worldwide crisis with nitrosamine contamination in medical products began in 2018. Therefore, trace-level analysis of nitrosamines is becoming an emerging topic of interest in the field of quality control. A novel GC-MS method with electron ionization and microextraction was developed and validated for simultaneous determination of nine carcinogenic nitrosamines (NDMA, NMEA, NDEA, NDBA, NMOR, NPYR, NPIP, NDPA, and -methyl-npz) in active pharmaceutical ingredients (APIs): cilostazol, sunitinib malate, and olmesartan medoxomil.

Thiogenistein-Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products.

Isoflavonoids such as genistein (GE) are well known antioxidants. The predictive biological activity of structurally new compounds such as thiogenistein (TGE)-a new analogue of GE-becomes an interesting way to design new drug candidates with promising properties. Two oxidation strategies were used to characterize TGE oxidation products: the first in solution and the second on the 2D surface of the Au electrode as a self-assembling TGE monolayer.

Cationic Emulsion Polymerization of Octamethylcyclotetrasiloxane (D4) in Mixtures with Alkoxysilanes.

The cationic emulsion polymerization of octamethylcyclotetrasiloxane (D4) in mixtures with methyltriethoxysilane (MTES) and vinyltriethoxysilane (VTES) was studied by FTIR ATR, GC, the development of a toluene insoluble fraction of the polymer and a gravimetric analysis. The polymerization of D4 alone was also conducted for comparison and, additionally, the development of molecular weight of polydimethylsiloxane (PDMS) obtained in that process was studied by GPC. Dodecylbenzenesulphonic acid (DBSA) was used as a surfactant and catalyst.

New Supramolecular Drug Carriers: The Study of Organogel Conjugated Gold Nanoparticles.

An aqueous solution of sodium citrate stabilized gold nanoparticles (AuNP) in the presence of lauroyl-L-alanine (CALA) forms a stable gel. The structure of the gel and the distribution profile of AuNP in it were analyzed. Will nanoparticles separated from each other with sodium citrate behave in the same way in solution and trapped in the gel matrix? Will the spatial limitation of solvent molecules aggregate nanoparticles and destroy their homogeneity? These questions are very important from the point of view of the use of gold nanoparticles, trapped in the gel structure as carriers of drugs in the slow-release process.

Combined Protein and Alkaloid Research of Latex Reveals CmMLP1 Accompanied by Alkaloids with Cytotoxic Potential to Human Cervical Carcinoma Cells.

L. is a latex-bearing plant used in traditional folk medicine to treat human papillomavirus (HPV)-caused warts, papillae, and condylomas. Its latex and extracts are rich in many low-molecular compounds and proteins, but there is little or no information on their potential interaction.

Anti-Cancer and Electrochemical Properties of Thiogenistein-New Biologically Active Compound.

Pharmacological and nutraceutical effects of isoflavones, which include genistein (GE), are attributed to their antioxidant activity protecting cells against carcinogenesis. The knowledge of the oxidation mechanisms of an active substance is crucial to determine its pharmacological properties. The aim of the present work was to explain complex oxidation processes that have been simulated during voltammetric experiments for our new thiolated genistein analog (TGE) that formed the self-assembled monolayer (SAM) on the gold electrode.

Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application.

An efficient method of thiol group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such genistein (), 5,11-dimethyl-5-indolo[2,3-b]quinolin (), capecitabine (), diosgenin (), tigogenin (), flumethasone (), fluticasone propionate (), ursolic acid methyl ester (), and β-sitosterol () was developed. In most cases, the desired compounds were obtained easily via two-step processes involving esterification reaction employing S-trityl protected thioacetic acid and the corresponding hydoxy-derivative, followed by removal of the trityl-protecting group to obtain the final compounds. The results of our preliminary experiments forced us to change the strategy in the case of genistein (), and the derivatization of diosgenin (), tigogenin (), and capecitabine () resulted in obtaining different compounds from those designed.

The ligand exchange of citrates to thioabiraterone on gold nanoparticles for prostate cancer therapy.

Cancer is one of the leading causes of morbidity and mortality worldwide and nanotechnology has a significant potential to enhance the therapeutic and diagnostic performance of anti-cancer agents. Our work offers a simple and feasible strategy for thiocompound nanomedicines to be used in cancer therapy. Novel gold nanoparticles conjugated with thioabiraterone (AuNP-S-AB) were synthesized and significant new analytical methodologies were developed for their characterization by UV-Vis, TEM, IR, NMR and TGA.

Design of Therapeutic Self-Assembled Monolayers of Thiolated Abiraterone.

The aim of our work was to synthetize of a new analogue of abiraterone-thiolated abiraterone (HS-AB) and design a gold surface monolayer, bearing in mind recent advances in tuning monolayer structures and using them as efficient drug delivery systems. Therapeutic self-assembled monolayers (TSAMs) were prepared by chemically attaching HS-AB to gold surfaces. Their properties were studied by voltammetry and atomic force microscopy (AFM).

Design and Molecular Modeling of Abiraterone-Functionalized Gold Nanoparticles.

The aim of our work was the synthesis and physicochemical characterization of a unique conjugate consisting of gold nanoparticles (AuNPs) and a pharmacologically active anticancer substance abiraterone (AB). The direct coupling of AB with gold constitutes an essential feature of the unique AuNPs⁻AB conjugate that creates a promising platform for applications in nanomedicine. In this work, we present a multidisciplinary, basic study of the obtained AuNPs⁻AB conjugate.

Use of the hyphenated LC-MS/MS technique and NMR/IR spectroscopy for the identification of exemestane stress degradation products during the drug development.

Exemestane (6-Methyleneandrosta-1,4-diene-3,17-dione) active pharmaceutical ingredient (EE-3) was subjected to thermal, photolytic, oxidative, acidic and base stress conditions prescribed by the ICH (International Conference on Harmonization) guideline Q1A(R2). EE-3 was found to degrade in base, acidic and oxidative conditions. Eleven new degradation products of EE-3 were characterized by the LC-MS/MS technique.

Pemetrexed conjugated with gold nanoparticles - Synthesis, characterization and a study of noncovalent interactions.

Gold nanoparticles (AuNPs) have been widely used as nanocarriers in drug delivery application. However, the binding mechanism between AuNPs and drug bases still remains a puzzle. Our study included: (i) optimization of three synthesis of the AuNPs-pemetrexed (PE) nanocomposites formation which was monitored by UV-Vis spectroscopy, (ii) identification of PE in gold nanocomposites and mechanism of PE interaction with gold nanoparticles by electrochemistry, NMR and Raman measurements, (iii) characterization of the three nanocomposites by TEM, DSL, ESL, zeta potential, XRPD and TGA analysis.

CE method for the in-process control of the synthesis of active substances conjugated with gold nanoparticles.

A fast capillary electrophoresis method was developed and validated for the in-process control (IPC) of the synthesis of active substances (APIs) with gold nanoparticles (AuNPs). The capillary electrophoresis method was key to ensure that the reaction step conducted in order to obtain AuNP and API conjugates will produce the expected product without the presence of free APIs, which is a critical parameter determining the quality of the synthetic material. Capillary electrophoresis was performed using uncoated fused-silica capillaries with the effective length of 40cm, 50μm i.

Synthesis and characterization of genistein conjugated with gold nanoparticles and the study of their cytotoxic properties.

Gold nanoparticles conjugated with drug substances are used in diagnostics and therapies. Apart from the combinations involving gold nanoparticles conjugated with drug substances through linkers, a direct bonding is also known. In our paper the example of such a direct bonding between gold nanoparticles and genistein (AuNPs-GE) is presented.

Casein kinase 2α regulates multidrug resistance-associated protein 1 function via phosphorylation of Thr249.

We have shown previously that the function of Ycf1p, yeast ortholog of multidrug resistance-associated protein 1 (MRP1), is regulated by yeast casein kinase 2α (Cka1p) via phosphorylation at Ser251. In this study, we explored whether casein kinase 2α (CK2α), the human homolog of Cka1p, regulates MRP1 by phosphorylation at the semiconserved site Thr249. Knockdown of CK2α in MCF7-derived cells expressing MRP1 [MRP1 CK2α(-)] resulted in increased doxorubicin sensitivity.

The G671V variant of MRP1/ABCC1 links doxorubicin-induced acute cardiac toxicity to disposition of the glutathione conjugate of 4-hydroxy-2-trans-nonenal.

Objective: Doxorubicin-induced acute cardiotoxicity is associated with the Gly671Val (G671V; rs45511401) variant of multidrug resistance-associated protein 1 (MRP1). Doxorubicin redox cycling causes lipid peroxidation and generation of the reactive electrophile, 4-hydroxy-2-trans-nonenal (HNE). Glutathione forms conjugates with HNE, yielding an MRP1 substrate, GS-HNE, whose intracellular accumulation can cause toxicity.

Validation of GC method for quantitative determination of residual 2-(2-chloroethoxy)ethanol (CEE) and N-methyl-2-pyrrolidinone (NMP) in pharmaceutical active substance.

The gas chromatography method with direct injection for quantitative determination of residual nonvolatile solvents such as 2-(2-chloroethoxy)ethanol (CEE) and N-methyl-2-pyrrolidinone (NMP) in quetiapine--the pharmaceutical active substance has been validated. Validation was performed according to the requirement of ICH validation guidelines Q2A and Q2B. Specificity, precision, accuracy, linearity, limits of detection and quantitation and robustness were determined and excellent results were obtained.

Suppression of cytochrome P450 reductase (POR) expression in hepatoma cells replicates the hepatic lipidosis observed in hepatic POR-null mice.

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR.