Tissue distribution of OL9-116, a Tdp1 inhibitor based on usnic acid, is significantly altered in Lewis lung carcinoma-bearing mice compared to healthy animals.

In the present study, we developed and validated three liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for quantification of the agent OL9-116, a Tdp1 inhibitor based on usnic acid, in murine lungs, liver and kidney, respectively. Additionally, a semi-quantitative method was developed for quantification of the agent in the primary tumor node of Lewis lung carcinoma. Tissue samples were prepared using ultrasonic homogenization and QuEChERS methodology.

Biostability, in vivo antiviral activity against respiratory syncytial virus, and pharmacokinetic profiles of (-)-borneol esters.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections, particularly in vulnerable populations such as infants and the elderly. In this study, we evaluated the metabolic stability, in vivo antiviral activity, and pharmacokinetic profiles of (-)-borneol esters, which were identified as potent RSV inhibitors through screening of a compound library. Two hit compounds, ST-2 and AS-645, caused a reduction in viral titers in RSV-infected mice.

Metabolomic and gene networks approaches reveal the role of mitochondrial membrane proteins in response of human melanoma cells to THz radiation.

Terahertz (THz) radiation has gained attention due to technological advancements, but its biological effects remain unclear. We investigated the impact of 2.3 THz radiation on SK-MEL-28 cells using metabolomic and gene network analysis.

Accumulation of Anthocyanin in the Aleurone of Barley Grains by Targeted Restoration of the Gene.

Blue barley grain pigmentation results from anthocyanin accumulation in the aleurone layer. Anthocyanins are known for their beneficial effects on human health. The gene encoding the MYELOCYTOMATOSIS 2 (MYC2) transcription factor is potentially responsible for the blue coloration of the aleurone.

AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Postoperative Delirium.

Despite considerable investigative efforts, the molecular mechanisms of postoperative delirium (POD) remain unresolved. The present investigation employs innovative methodologies for identifying potential primary and secondary metabolic markers of POD by analyzing serum metabolomic profiles utilizing the genetic algorithm and artificial neural networks. The primary metabolomic markers constitute a combination of metabolites that optimally distinguish between POD and non-POD groups of patients.

Constitutive Androstane Receptor Agonist Initiates Metabolic Activity Required for Hepatocyte Proliferation.

Activation of the constitutive androstane receptor (CAR, NR1I3) by chemical compounds induces liver hyperplasia in rodents. 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a mouse CAR agonist, is most often used to study chemically induced liver hyperplasia and hepatocyte proliferation in vivo. TCPOBOP is a potent murine liver chemical mitogen, which induces rapid liver hyperplasia in mice independently of liver injury.

Pharmacokinetic study of Tdp1 inhibitor resulted in a significant increase in antitumor effect in the treatment of Lewis lung carcinoma in mice by its combination with topotecan.

We have previously shown that the Tdp1 inhibitor, enamine derivative of usnic acid, the agent OL9-116, enhances the antitumor activity of topotecan. In the present study, we developed and validated LC-MS/MS method for the quantification of OL9-116 in mouse whole blood and studied pharmacokinetics of the agent. The substance OL9-116 was shown to be stable in the whole blood in vitro.

Global LC-MS/MS targeted metabolomics using a combination of HILIC and RP LC separation modes on an organic monolithic column based on 1-vinyl-1,2,4-triazole.

The paper presents an LC-MS/MS-based approach to targeted screening of both polar and non-polar metabolites using a synthesized monolithic column which is a copolymer of styrene, divinylbenzene, and 1-vinyl-1,2,4-triazole. It was shown that this column in combination with eluents 20 mM (NH)CO + NH (pH = 9.8, eluent A) and ACN (eluent B) allows for separation of metabolites of different nature in two modes, HILIC and RP LC, and these methods are mutually complementary.

Development of an LC-MS/MS-based method for quantification and pharmacokinetics study on SCID mice of a dehydroabietylamine-adamantylamine conjugate, a promising inhibitor of the DNA repair enzyme.

Earlier, it was found that the agent KS-389, a conjugate of dehydroabietylamine and 1-aminoadamantane, possess inhibiting activity with regard to Tdp1. It this study, LC-MS/MS-based methods of quantification of KS-389 in mice blood and several organs (brain, liver and kidney) were developed and validated. Validation of the methods was performed according to the guidelines of U.

Ligand-free Ullmann-type arylation of oxazolidinones by diaryliodonium salts.

The arylation of azaheterocycles can be considered as one of the most important processes for the preparation of various biologically active compounds. In the present work, we describe a method for the copper-catalyzed -arylation of hindered oxazolidinones using diaryliodonium salts. The method succeeds in good to excellent yields for the arylation of 4-alkyloxazolidinones, including sterically hindered isopropyl- and -butyl-substituted.

A Newly Identified Monoterpenoid-Based Small Molecule Able to Support the Survival of Primary Cultured Dopamine Neurons and Alleviate MPTP-Induced Toxicity .

Parkinson's disease (PD) is the most common age-related movement disorder characterized by the progressive loss of nigrostriatal dopaminergic neurons. To date, PD treatment strategies are mostly based on dopamine replacement medicines, which can alleviate motor symptoms but do not slow down the progression of neurodegeneration. Thus, there is a need for disease-modifying PD therapies.

Stability Study, Quantification Method and Pharmacokinetics Investigation of a Coumarin-Monoterpene Conjugate Possessing Antiviral Properties against Respiratory Syncytial Virus.

The stability of a new coumarin derivative, agent K-142, bearing α-pinene residue and possessing antiviral activity against respiratory syncytial virus (RSV) was studied in whole mice blood in vitro, and a method for its quantification in this matrix was developed and validated. The sample preparation method was precipitation of whole blood with a mixture of 0.2 M ZnSO with MeOH (2:8 /) containing 2-adamantylamine hydrochloride as an internal standard (IS).

Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses.

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S.

Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses.

When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance.

Novel Bispidine-Monoterpene Conjugates-Synthesis and Application as Ligands for the Catalytic Ethylation of Chalcones.

A number of new chiral bispidines containing monoterpenoid fragments have been obtained. The bispidines were studied as ligands for Ni-catalyzed addition of diethylzinc to chalcones. The conditions for chromatographic analysis by HPLC-UV were developed, in which the peaks of the enantiomers of all synthesized chiral products were separated, which made it possible to determine the enantiomeric excess of the resulting mixture.

Stability study of the antiviral agent camphecene in dried blood spots at different temperatures.

In this study, an optimized procedure of sample preparation for quantitative determination of the antiviral agent camphecene in dried rat blood spots was developed. It has been shown that when using methanol containing 0.1% HCOOH as an extractant, the recovery of the substance increases in comparison with the previously developed method.

Biostability study, quantitation method and preliminary pharmacokinetics of a new antifilovirus agent based on borneol and 3-(piperidin-1-yl)propanoic acid.

The stability of the new antifiloviral agent AS-358, which is a derivative of borneol and 3-(piperidin-1-yl)propanoic acid, was studied in the blood and blood plasma of rats in vitro. It was found that both in the blood and in the plasma stabilized by EDTA or heparin, the compound is rapidly hydrolyzed at the ester bond. When sodium fluoride was added to the whole blood, the decomposition of the compound was significantly slowed down, which made it possible to develop and validate a method for the quantitative determination of the agent in this matrix.

Changes in Amino Acid and Acylcarnitine Plasma Profiles for Distinguishing Patients with Multiple Sclerosis from Healthy Controls.

McDonald criteria and magnetic resonance imaging (MRI) are used for the diagnosis of multiple sclerosis (MS); nevertheless, it takes a considerable amount of time to make a clinical decision. Amino acid and fatty acid metabolic pathways are disturbed in MS, and this information could be useful for diagnosis. The aim of our study was to find changes in amino acid and acylcarnitine plasma profiles for distinguishing patients with multiple sclerosis from healthy controls.

Development and validation of an LC-MS/MS method for the quantitative analysis of the anti-influenza agent camphecene in rat plasma and its application to study the blood-to-plasma distribution of the agent.

A method of quantitative determination of camphecene, a new anti-influenza agent, in rat blood plasma based on LC-MS/MS was developed, validated and used to study the distribution of the agent between blood cells and blood plasma. The method was validated according to FDA and EMA recommendations in terms of selectivity, linearity, accuracy, precision, recovery, stability and carry-over. Plasma samples were precipitated with methanol followed by the addition of a methanolic solution of 2-adamantylamine hydrochloride (internal standard).

Targeted metabolomics approach for identification of relapsing-remitting multiple sclerosis markers and evaluation of diagnostic models.

Multiple sclerosis (MS) is an inflammatory autoimmune disease that causes demyelination of nerve cell axons. This paper is devoted to the study of relapsing-remitting multiple sclerosis (RRMS) biomarkers using an LC-MS/MS-based targeted metabolomics approach and the assessment of changes in the profile of 13 amino acids and 29 acylcarnitines in plasma during the relapse of the disease. A significant increase ( < 0.

Comparison of dried matrix spots and fabric phase sorptive extraction methods for quantification of highly potent analgesic activity agent (2R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol in rat whole blood and plasma using LC-MS/MS.

The methods for quantification of highly potent analgesic agent (2R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol in rat whole blood and plasma were developed and validated using dried matrix spots (DMS) or fabric phase sorptive extraction (FPSE) techniques in combination with LC-MS/MS. 2-Adamantylamine hydrochloride was used as an internal standard (IS). Chromatographic separation was carried out on a reversed-phase column (2.

Untargeted search and identification of metabolites of antiviral agent camphecene in rat urine by liquid chromatography and mass spectrometry and studying their distribution in organs following peroral administration of the compound.

Major metabolites of camphecene, a new effective antiviral agent, formed after its oral administration to rats and excreted in the urine, were found and identified using liquid chromatography coupled to mass spectrometry as well as multivariate analysis of HPLC-MS data. The metabolites were found to be camphecene glucuronide, camphecene sulfate and the corresponding iminoacid. A study of the dynamics of accumulation of camphecene and its metabolites in the liver, kidneys, lungs and brain of animals was performed.