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Relapsing–remitting multiple sclerosis markers determined (a) and multivariate models for early diagnosis were evaluated (b).

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. For the compounds that showed activity on the pseudoviral system, a study using three strains of the infectious SARS-CoV-2 virus was carried out. As a result, two leader compounds were found that showed activity on the Wuhan, Delta, and Omicron strains. Based on the biological results, we searched for the potential binding site of the leader compounds using molecular dynamics and molecular docking methods. We suggested that the compounds can bind in conserved regions of the central helices and/or heptad repeats of glycoprotein S of SARS-CoV-2 viruses.

A series of secondary amines combining monoterpenoid and aminoadamantane moieties have been synthesized. Their cytotoxic activity against human cancer cells CEM-13, MT-4, and U-937 has been studied for the first time. Most of the obtained compounds exhibited a significant cytotoxic activity with the median cytotoxic dose (CTD50) ranging from 6 to 84 µM. The most promising results were obtained for compound 2b which was synthesized from 1-aminoadamantane and (-)-myrtenal and revealed a high activity against all tumor lines used (CTD50 = 12 ÷ 21 µM) along with low toxicity with respect to MDCK cells (CTD50 = 1500 µM). The synthesized amines do not exert the genotoxic effect on cells of the biosensor strain based on recombinant E. coli cells bearing the pRAC-gfp plasmid.

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This work compares the metabolic profiles of plasma and the cerebrospinal fluid (CSF) of the patients with high-grade (III and IV) gliomas and the conditionally healthy controls using the wide-range targeted screening of low molecular metabolites by HPLC-MS/MS. The obtained data were analyzed using robust linear regression with Huber’s M-estimates, and a number of metabolites with correlated content in plasma and CSF was identified. The statistical analysis shows a significant correlation of metabolite content in plasma and CSF samples for the majority of metabolites. Several metabolites were shown to have high correlation in the control samples, but not in the glioma patients. This can be due to the specific metabolic processes in the glioma patients or to the damaged integrity of blood-brain barrier. The results of our study may be useful for the understanding of molecular mechanisms underlying the development of gliomas, as well as for the search of potential biomarkers for the minimally invasive diagnostic procedures of gliomas.

The electrochemical reduction of 3,3´ bi(2 R 5,5 dimethyl 4 oxopyrrolinylidene) 1,1´ dioxides (R = CF 3 , Me, Ph, Bu t ), which are cyclic dinitrons with conjugated С=С bond, in acetonitrile is an EE process producing stable radical anions and dianions, whereas the electrochemical oxidation is an EEC (R = Me, Ph) or EE process (R = Bu t ) with formation of radical cations (except for the case of R = CF 3 ) and dications (R = Bu t ) stable under standard conditions. Radical cations of the dioxides with R = Me, Ph, and Bu t and radical anions of the whole series of the compounds studied, including R = CF 3 , were characterized by ESR spectroscopy combined with electrochemical measurements and quantum chemical calcula tions. The electrochemical behavior of the Bu t substituted dinitron is unique: the EE processes in the region of negative and positive potentials with formation of the dianion, radical anion, radical cation, and dication stable at Т = 298 K were observed for the first time within one cycle of potential sweep in the CV curve measured in MeCN.It has previously 1 been shown that 3,3´ bi(2 R 5,5 di methyl 4 oxopyrrolinylidene) 1,1´ dioxides 1-4, being cyclic dinitrons with conjugated C=C bond, have a con siderable electron withdrawing ability comparable with that of tetracyanoethylene, 2 and their electrochemical re duction (ECR) in DMF is an EE process (includes two one electron electrochemical steps) with formation of radical anions (RA) and dianions (DA) stable at Т = 298 K.The one electron reduction of dinitrons 1-4 is ac companied by the formation of the corresponding RA detected in the ESR spectra. According to these data, in the radical anion states, the substituents in positions 2 of the pyrrolinone rings disturb weakly the π system O←N=C-C=C-C=N→O, both 14 N nuclei are spec trally equivalent, the corresponding isotropic hyperfine interaction (IHFI) constants a N are close in magnitude and vary in a range of ±0.004 mT with R variation, and hyperfine coupling with the substituent nuclei appears only in the cases of R = CF 3 and Me.Dinitrons 1-4 are formed due to the mild chemical oxidation of the starting pyrrolinones 5. 3 The extension of the π system in compounds 1-4 compared to the starting pyrrolinones should decrease an energy gap between the levels of the frontier MOs (∆ε = ε LUMO -ε HOMO , LUMO and HOMO are the lowest unoc cupied and highest occupied MOs, respectively) and result in an easier one electron oxidation and, prob ably, stabilization of the positively charged molecular ions (cf. Ref. 4).To study a possibility of formation and estimate stability limits of radi cal cations (RC) and dications (DC), we studied the electro chemical oxidation (ECO) and, for comparison, ECR of compounds 1-4 in MeCN by cyclic voltammetry (CV) and ESR spectroscopy. ExperimentalCyclic voltammograms of dinitrons 1-4 were measured on an SVA 1BM electrochemical system (Bulgaria) equipped with a LAB MASTER polyfunctional interface (Institute of Nuclear Physics, Novosibirsk, Russia), which enables one complete d...