Treatment-resistant schizophrenia (TRS) is an important and unresolved problem in biological and clinical psychiatry. Approximately 30% of cases of schizophrenia (Sch) are TRS, which may be due to ...the fact that some patients with TRS may suffer from pathogenetically “non-dopamine” Sch, in the development of which neuroinflammation is supposed to play an important role. The purpose of this narrative review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines during the development of therapeutic resistance to APs and their pathogenetic and prognostic significance of cytokine imbalance as TRS biomarkers. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to maintaining or changing the cytokine balance can become a new key in unlocking the mystery of “non-dopamine” Sch and developing new therapeutic strategies for the treatment of TRS and psychosis in the setting of acute and chronic neuroinflammation. In addition, the inconsistency of the results of previous studies on the role of pro-inflammatory and anti-inflammatory cytokines indicates that the TRS biomarker, most likely, is not the serum level of one or more cytokines, but the cytokine balance. We have confirmed the hypothesis that cytokine imbalance is one of the most important TRS biomarkers. This hypothesis is partially supported by the variable response to immunomodulators in patients with TRS, which were prescribed without taking into account the cytokine balance of the relation between serum levels of the most important pro-inflammatory and anti-inflammatory cytokines for TRS.
Tertiary diethylpyridylphosphine was synthesized by the reaction of pyridylphosphine with bromoethane in a suberbasic medium. The reaction of phosphine with the copper(I) iodide led to the formation ...of a copper(I) coordination polymer, which, according to the X-ray diffraction data, has an intermediate structure with a copper-halide core between the octahedral and stairstep geometries of the Cu
I
clusters. The obtained coordination polymer exhibits a green emission in the solid state, which is caused by the
(M+X)LCT transitions. The heating up of the copper(I) coordination polymer to 138.5 °C results in its monomerization and the formation of a new solid-state phase. The new phase exhibits a red emission, with the emission band maximum at 725 nm. According to the experimental data and quantum chemical computations, it was concluded that depolymerization probably leads to a complex that is formed with the octahedral structure of the copper-halide core. The resulting solid-state phase can be backward-converted to the polymer phase via recrystallization from the acetone or DMF. Therefore, the obtained coordination polymer can be considered a sensor or detector for the overheating of processes that should be maintained at temperatures below 138 °C (e.g., engines, boiling liquids, solar heat systems, etc.).
In this article, we report a highly regioselective method for the synthesis of new fused pyridine derivatives2,3-disubstituted quinolines and 1,2-dihydro-3H-pyrazolo3,4-bpyridin-3-one derivatives. ...The method is based on the reaction of 1,1-diethoxybutane derivatives with aromatic and heterocyclic nucleophiles. The isolated compounds are similar to the products formed as a result of the Debner–Miller reaction. However, we have shown that the interaction of 1,1-diethoxybutane derivatives with (hetero)aromatic amines proceeds according to a mechanism different from that of the Doebner–Miller reaction. The proposed method is distinguished by the possibility of obtaining a wide range of substituted quinolines and 1,2-dihydro-3H-pyrazolo3,4-bpyridin-3-one derivatives in one step, the absence of the need to use expensive metal-containing catalysts, and a high product yield.
A family of helical dinuclear copper(
i
) pyridylphospholane complexes Cu
2
L
3
XX (X = BF
4
−
, Cl
−
and Br
−
) was prepared. The family includes the first examples of this type of complex based on ...copper(
i
) chloride and copper(
i
) bromide. The two isomers typical of this class of compounds, namely head-to-head and head-to-tail complexes, were studied in solution by spectroscopic and optical methods, and in the solid state by X-ray diffraction. Furthermore, the solid-state luminescence of the complexes at different temperatures was studied, and the results were interpreted using quantum-chemical calculations. It was shown that the luminescence of the complexes is attributed to the
3
(M + X)LCT transitions.
The current work presents novel dinuclear Cu(
i
) complexes bearing P,N-ligands. Their structures, isomerization, and photophysical properties are discussed in detail.
Among neurological adverse reactions in patients with schizophrenia treated with antipsychotics (APs), drug-induced parkinsonism (DIP) is the most common motility disorder caused by drugs affecting ...dopamine receptors. One of the causes of DIP is the disruption of neurotransmitter interactions that regulate the signaling pathways of the dopaminergic, cholinergic, GABAergic, adenosinergic, endocannabinoid, and other neurotransmitter systems. Presently, the development mechanisms remain poorly understood despite the presence of the considered theories of DIP pathogenesis.
The utility of sterically hindered phenols (SHPs) in drug design is based on their chameleonic ability to switch from an antioxidant that can protect healthy tissues to highly cytotoxic species that ...can target tumor cells. This work explores the biological activity of a family of 45 new hybrid molecules that combine SHPs equipped with an activating phosphonate moiety at the benzylic position with additional urea/thiourea fragments. The target compounds were synthesized by reaction of iso(thio)cyanates with C-arylphosphorylated phenols containing pendant 2,6-diaminopyridine and 1,3-diaminobenzene moieties. The SHP/urea hybrids display cytotoxic activity against a number of tumor lines. Mechanistic studies confirm the paradoxical nature of these substances which combine pronounced antioxidant properties in radical trapping assays with increased reactive oxygen species generation in tumor cells. Moreover, the most cytotoxic compounds inhibited the process of glycolysis in SH-SY5Y cells and caused pronounced dissipation of the mitochondrial membrane of isolated rat liver mitochondria. Molecular docking of the most active compounds identified the activator allosteric center of pyruvate kinase M2 as one of the possible targets. For the most promising compounds, 11b and 17b, this combination of properties results in the ability to induce apoptosis in HuTu 80 cells along the intrinsic mitochondrial pathway. Cyclic voltammetry studies reveal complex redox behavior which can be simplified by addition of a large excess of acid that can protect some of the oxidizable groups by protonations. Interestingly, the re-reduction behavior of the oxidized species shows considerable variations, indicating different degrees of reversibility. Such reversibility (or quasi-reversibility) suggests that the shift of the phenol-quinone equilibrium toward the original phenol at the lower pH may be associated with lower cytotoxicity.
A first successful synthesis of 2‐(pyrazolyl)pyrrolidines is reported starting from readily available reagents. A wide variety of N‐substituted 2‐(pyrazolyl)pyrrolidines are obtained with up to 96 % ...yield. The influence of the obtained compounds on biofilm formation by V. aquamarinus DSM 26054 and A. calcoaceticus VKPM B–10353 have been studied. Some of the tested compounds were found to suppress the growth of bacterial biofilms at nanomolar concentrations and thus are promising candidates for further studies.
A first successful synthesis of 2‐(pyrazolyl)pyrrolidines via a metal‐free approach is reported. The proposed approach relies on intramolecular imination / nucleophilic trapping of 4‐aminobutanal acetals with pyrazolones and provides easy entry to the previously unknown class of 2‐(hetaryl) substituted pyrrolidines.
Valproic acid (VPA) and its salts (sodium calcium magnesium and orotic) are psychotropic drugs that are widely used in neurology and psychiatry. The long-term use of VPA increases the risk of ...developing adverse drug reactions (ADRs), among which metabolic syndrome (MetS) plays a special role. MetS belongs to a cluster of metabolic conditions such as abdominal obesity, high blood pressure, high blood glucose, high serum triglycerides, and low serum high-density lipoprotein. Valproate-induced MetS (VPA-MetS) is a common ADR that needs an updated multidisciplinary approach to its prevention and diagnosis. In this review, we consider the results of studies of blood (serum and plasma) and the urinary biomarkers of VPA-MetS. These metabolic biomarkers may provide the key to the development of a new multidisciplinary personalized strategy for the prevention and diagnosis of VPA-MetS in patients with neurological diseases, psychiatric disorders, and addiction diseases.
Reactions of pyridoxal with aromatic diamines Bagautdinova, Roza Kh; Kibardina, Lyudmila K.; Burilov, Alexander R. ...
Chemistry of heterocyclic compounds (New York, N.Y. 1965),
03/2020, Volume:
56, Issue:
3
Journal Article
Peer reviewed
Pyridoxal monoimines were obtained by the reaction of pyridoxal with aromatic diamines. A change in the ratio of the reagents or introduction of another aromatic aldehyde into the reaction leads to ...the formation of symmetric and asymmetric diimines. In some cases, the initially formed diimines are transformed into the corresponding benzimidazoles. The products of the reaction of pyridoxal with 1,3-diaminobenzene have a furopyridine structure.
To obtain new polyfunctional inhibitors of radical-chain oxidative processes, C- and N-benzylation of a number of phosphorylacetic acid hydrazide derivatives is realized in their reactions with ...3,5-di-tert-butyl-4-hydroxybenzyl acetate. N-benzylation of mixtures of Z and E isomers of hydrazones of phosphorylacetic acid derivatives proceeds stereoselectively with the formation of only E
C=N
isomers.
