HDAC3_VS_assistant: cheminformatics-driven discovery of histone deacetylase 3 inhibitors.

Histone deacetylase 3 (HDAC3) inhibitors keep significant therapeutic promise for treating oncological, neurodegenerative, and inflammatory diseases. In this work, we developed robust QSAR regression models for HDAC3 inhibitory activity and acute toxicity (LD, intravenous administration in mice). A total of 1751 compounds were curated for HDAC3 activity, and 15,068 for toxicity.

Bilirubin: Photophysical and photochemical properties, phototherapy, analytical methods of measurement. A short review.

Bilirubin, a yellow bile pigment, plays an important role in the body, being a potent antioxidant and having anti-inflammatory, immunomodulatory, cytoprotective, and neuroprotective functions. This makes bilirubin promising as a therapeutic and diagnostic agent in biomedicine. However, excess bilirubin is toxic and should be removed from the body.

Conjugates of amiridine and salicylic derivatives as promising multifunctional CNS agents for potential treatment of Alzheimer's disease.

New conjugates of amiridine and salicylic derivatives (salicylamide, salicylimine, and salicylamine) with different lengths of alkylene spacers were designed, synthesized, and evaluated as potential multifunctional central nervous system therapeutic agents for Alzheimer's disease (AD). Conjugates demonstrated high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition (IC: AChE, 0.265-4.

N-Aryl Benzimidazole and Benzotriazole Derivatives and Their Hybrids as Cytotoxic Agents: Design, Synthesis and Structure-Activity Relationship Studies.

The era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is currently the creation of hybrid molecules containing several pharmacophore fragments of different structures. This strategy is successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce side effects.

Proposed Mechanisms of Cell Therapy for Alzheimer's Disease.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches.

2-Arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropanoic acids as selective and effective carboxylesterase inhibitors with powerful antioxidant potential.

A series of 2-arylhydrazinylidene-3-oxo acids (AHOAs) was prepared by dealkylation of alkyl-2-arylhydrazinylidene-3-oxo-3-alkanoates with AlBr. Using X-Ray, NMR spectroscopy, and quantum mechanical calculations (QM), the existence of AHOAs in a thermodynamically favorable Z-form stabilized by two intramolecular H-bonds was established. All AHOAs had acceptable ADME parameters.

Clamshell-type bis-phthalocyanines as colour-changing optical limiters: TDDFT modelling of electrically induced absorption for real-time colour indication of optical limiter efficiency in nonlinear laser protection.

This paper presents an innovative method for assessing the performance of optical limiters, which are devices that protect humans against laser radiation. The essence of the process is that with increasing laser radiation intensity, the colour of nonlinear absorbers, the working components of these devices, can change in contrast to the original one, which was demonstrated by quantum-chemical linear response time-dependent density functional theory (LR-TDDFT) for molecules excited by static electric finite fields (FF) within the general DFT (density functional theory) approach. Modelling was carried out on clamshell-type bis-phthalocyanines, in which the macrocycles are strapped by a cyclotriphosphazene spacer, suitable candidates for creating nonlinear optical (NLO) dyes for laser technology.

Effect of the stability of 1,3-bis(diphenylphosphoryl)-2-oxapropane complexes on the separation of lanthanide ions and their detection.

Phosphoryl podands of neutral type with a flexible ethylene glycol chain and diphenylphosphorylmethyl end groups are known for their complexation properties towards various cations. In this work, the complexation process between 1,3-bis(diphenylphosphoryl)-2-oxapropane (L) and lanthanide ions was studied. Namely, the stability constants of lanthanide complexes with L in acetonitrile were estimated by the method of spectrophotometric titration.

Analysis of the brain transcriptome, microbiome and metabolome in ketogenic diet and experimental stroke.

The ketogenic diet (KD) has been shown to be effective in treating various brain pathologies. In this study, we conducted detailed transcriptomic and metabolomic profiling of rat brains after KD and ischemic stroke in order to investigate the effects of KD and its underlying mechanisms. We evaluated the effect of a two-month KD on gene expression in intact brain tissue and after middle cerebral artery occlusion (MCAO).

Thermosensitive injectable fibrillar gels based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) as biocompatible brain implants.

Drug treatment of glioblastoma, the most aggressive and widespread form of brain cancer, is complicated due to the difficulty of penetration of chemotherapeutic drugs through the blood-brain barrier (BBB). Moreover, with surgical removal of tumors, in 90 % of cases they reappear near the original focus. To solve this problem, we propose to use hydrogel based on cellulose nanocrystals grafted with poly(N-isopropylacrylamide) (CNC-g-PNIPAM) as a promising material for filling postoperative cavities in the brain with the release of antitumor drugs.

Neuroprotective thiourea derivative uncouples mitochondria and exerts weak protonophoric action on lipid membranes.

The isothiourea derivative NT-1505 is known as a neuroprotector and cognition enhancer in animal models of neurodegenerative diseases. Bearing in mind possible relation of the NT-1505-mediated neuroprotection to mitochondrial uncoupling activity, here, we examine NT-1505 effects on mitochondria functioning. At concentrations starting from 10 μM, NT-1505 prevented Ca-induced mitochondrial swelling, similar to common uncouplers.

Efficient synthesis and evaluation of therapeutic potential of fluorine containing 2-arylchromen-4-ones.

A large series of 2-arylchromen-4-ones containing from 1 to 3 fluorine atoms or a trifluoromethyl group in the structure was synthesized by condensation of fluorinated 2-hydroxyacetophenones with benzaldehydes in an alkaline medium and subsequent oxidative cyclization of the resulting 2'-hydroxychalcones by action of I in DMSO. The cytotoxicity of the obtained compounds was studied in glioblastoma cell line, SNB19, and in a monkey-derived normal kidney epithelium cell line, Vero. In addition, antiglycation activity of the obtained compounds was evaluated.

HT_PREDICT: a machine learning-based computational open-source tool for screening HDAC6 inhibitors.

Histone deacetylase 6 (HDAC6) is a promising drug target for the treatment of human diseases such as cancer, neurodegenerative diseases (in particular, Alzheimer's disease), and multiple sclerosis. Considerable attention is paid to the development of selective non-toxic HDAC6 inhibitors. To this end, we successfully form a set of 3854 compounds and proposed adequate regression QSAR models for HDAC6 inhibitors.

Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells.

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones.

Combined Ionizing Radiation Exposure by Gamma Rays and Carbon-12 Nuclei Increases Neurotrophic Factor Content and Prevents Age-Associated Decreases in the Volume of the Sensorimotor Cortex in Rats.

In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.

Discovery of Di(het)arylmethane and Dibenzoxanthene Derivatives as Potential Anticancer Agents.

A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related oxygen-containing heterocycles. These compounds demonstrated selective antitumor activity associated with the induction of cell apoptosis and inhibition of the process of glycolysis. In particular, bis(heteroaryl)methane containing two 4-hydroxy-6-methyl-2-pyran-2-one moieties combine excellent in vitro antitumor efficacy with an IC of 1.

Target-Oriented Synthesis of Triphenylphosphine Functionalized Carbon Dots with Negative Charge for ROS Scavenging and Mitochondrial Targeting.

Triphenylphosphine functionalized carbon dots (TPP-CDs) showcase robust mitochondria targeting capacity owing to their positive electrical properties. However, TPP-CDs typically involve complicated synthesis steps and time-consuming postmodification procedures. Especially, the one-step target-oriented synthesis of TPP-CDs and the regulation of TPP linkage modes remain challenges.

Analysis of Natural Antibodies during the Development of Phantom Pain Syndrome.

We determined natural antibodies (n-Abs) to the regulators of the main systems of biochemical homeostasis: β-endorphin, serotonin, dopamine, histamine, orphanin, angiotensin, GABA, glutamate, bradykinin, vasopressin, thrombin, and α-2-macroglobulin in individuals with phantom pain syndrome (PPS), resulting from amputation after injury. It was established that each patient has an individual immunoprofile, but for all of them there was a significant increase in the level of antibodies to serotonin, histamine, and angiotensin, which reflect the chronicity of the pain syndrome and do not depend on the self-assessment of the severity of PPS. Determination of the role of regulators of biochemical homeostasis in the development of phantom pain showed that, at high, moderate, and weak severity of PPS, the biogenic amine and angiotensinergic systems are activated.

Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.

Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α.

Catalytically Active SiO Aerogels Comprising Chelate Complexes of Palladium.

A series of silica-based aerogels comprising novel bifunctional chelating ligands was prepared. To produce target aerogels, two aminosilanes, namely (3-aminopropyl)trimethoxysilane (APTMS) and -(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAPTMS), were acylated by natural amino acids (()-(+)-2-phenylglycine or -phenylalanine), followed by gelation and supercritical drying (SCD). Lithium tetrachloropalladate was used as the metal ion source to prepare strong complexes of Pd with amino acids covalently bonded to a silica matrix.

Nature-Inspired 1-Phenylpyrrolo[2,1-]isoquinoline Scaffold for Novel Antiproliferative Agents Circumventing P-Glycoprotein-Dependent Multidrug Resistance.

Previous studies have shown that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in some tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, several novel substituted 1-Ph-DHPIQ derivatives were synthesized which carry carboxylate groups (COOH, COOEt), nitrile (CN) and Mannich bases (namely, morpholinomethyl derivatives) in the C2 position, as replacements of the already reported aldehyde group. They were evaluated for antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and for the ability of selectively inhibiting P-gp-mediated MDR.

Disruption of Electroencephalogram Coherence between Cortex/Striatum and Midbrain Dopaminergic Regions in the Knock-Out Mice with Combined Loss of Alpha, Beta, and Gamma Synucleins.

Unlabelled: The malfunctioning of the brain synucleins is associated with pathogenesis of Parkinson's disease. Synucleins' ability to modulate various pre-synaptic processes suggests their modifying effects on the electroencephalogram (EEG) recorded from different brain structures. Disturbances in interrelations between them are critical for the onset and evolution of neurodegenerative diseases.

Animal Models of FUS-Proteinopathy: A Systematic Review.

Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment.