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The condensation of 3-formylchromones and 6-amino-5-((3,5-di-tert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)amino)-1,3-dimethyl-pyrimidine-2,4(1H,3H)-dione allowed us to synthesize chromone based hybrids containing additional pharmacophores - xanthine and sterically hindered phenol fragments. Novel compounds have been characterized by 1H and 13C NMR spectroscopy, mass spectrometry and elemental analysis. The molecular structure of compound 2 was determined by single crystal X-ray diffraction studies. Compounds 2-9, 11, 12 exhibit cytotoxic activity against human colon carcinoma cells HCT116 and breast carcinoma cells MCF7 at submicromolar concentrations. Compound 11 containing 6,8-dimethylchromone core has the highest cytotoxicity against tumor cells and lowest at non-tumor fibroblasts - this is leader compound of the obtained series with acceptable in vitro selectivity. Synthesized compounds exhibit antioxidant activity comparable to the reference drug Trolox. Combination of promising antioxidant activity and a selective antitumor cytotoxicity in vitro determines the prospects of these compounds as chemotherapy agents.

The aim of the study. To evaluate the effect of succinic acid derivatives on changes of mitochondrial function in rats under cerebral ischemia conditions. Materials and methods. In this work, the effect of succinic acid, ethylmethylhydroxypyridine succinate, and acetylaminosuccinic acid at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg (per os) on the change of the neuronal mitochondria function was studied. Cerebral ischemia was reproduced by the Tamura method. The following parameters were evaluated: changes in aerobic/anaerobic metabolism, mitochondrial membrane potential, the opening rate of the mitochondrial pore of transitional permeability and the activity of apoptotic systems. Results. During the study, it was found that the use of the test-compounds at doses of 100 mg/kg and 200 mg/kg contributed to an increase in ATP-generating activity, as well as the maximum respiration level and respiratory capacity, while accompanied by a decrease in the intensity of anaerobic metabolism reactions. Also, upon administration of the test succinic acid derivatives, an increase in the mitochondrial membrane potential and latent opening time of the mitochondrial pore transitional permeability were observed. Moreover, the activity of caspase-3 and apoptosis-inducing factor on groups treated by test objects at doses of 100 mg/kg and 200 mg/kg was significantly lower than that in untreated animals. Conclusion. The studied succinic acid derivatives contribute to the restoration of mitochondrial function in cerebral ischemia conditions, while the most effective dose can be considered to be 100 mg/kg.

Background: Alzheimer’s disease is the main form of dementia, which affects more than46 million people every year. In the pathogenesis of Alzheimer’s disease, a significant roleplayed mitochondrial dysfunction, which is a promising pharmacotherapeutic target ofneuroprotective therapy. In this regard, this study aimed to evaluate the effect of the 4-hydroxy-3,5-ditretbutyl cinnamic acid on changes of mitochondrial function in experimental Alzheimer’sdisease induced by Aβ injection in rats. Methods: Alzheimer’s disease was modeled on Wistar rats by injecting a fragment of β-amyloid(Aß 1-42) into the CA1 part of the hippocampus. The test-compound (4-hydroxy-3,5-ditretbutylcinnamic acid, 100 mg/kg, per os) and the reference drugs (resveratrol, 20 mg/kg, per os andEGB671, 100 mg/kg, per os) were administered for 60 days after surgery. The restoration of amemorable trace in animals was evaluated in the Morris water maze test. The concentrationof β -amyloid, Tau-protein, and changes in parameters characterizing mitochondrial function(cellular respiration, concentration of mitochondrial ROS, activity of apoptosis reactions(caspase-3 and apoptosis induced factor) were also determined. Results: This study showed that the administration of 4-hydroxy-3,5-ditretbutyl cinnamic acidat a dose of 100 mg/kg (per os) in rats with reproduced Alzheimer’s disease contributed to thenormalization of mitochondrial respiratory function. It was expressed in the normalizationof aerobic metabolism, increased activity of respiratory complexes and stabilization ofmitochondrial membrane potential. Also, when animals were treated with 4-hydroxy-3,5-ditretbutyl cinnamic acid, there was a decrease in the concentration of intracellular calcium(by 39.7% (p

The aim of the study was to assess the effect of certain derivatives of cinnamic acids on changes of the tricarboxylic acid cycle enzymes activity under experimental cerebral ischemia. Materials and methods. Brain ischemia was modeled by irreversible right-sided coagulation of the middle cerebral artery. Test compounds: 4-hydroxy-3,5-ditretbutyl cinnamic acid, coumaric, coffee, synapic, cinnamic, 4-hydroxycinnamic and ferulic acids, as well as a reference drug — succinic acid was administered at a dose of 100 mg / kg per os for 3 days after the reproduction of ischemia. Then, changes in the activity of aconitase, citrate synthase, and α-ketoglutarate dehydrogenase were evaluated in the supernatant of the brain. Results. The use of all the studied compounds and the reference drug helped to restore the activity of enzymes of the tricarboxylic acid cycle. The most pronounced results were obtained when animals were treated by 4-hydroxy-3,5-ditretbutyl cinnamic acid, against the background of which the activity of citrate synthase was higher than in animals treated by succinic, coumaric, coffee, synapic and ferulic acids by 1.53 ( p < 0.05), 1.41 ( p < 0.05), 1.4 ( p < 0.05), 1.46 ( p < 0.05) and 1.41 ( p < 0.05) times, respectively. Also, with the administration of 4-hydroxy-3,5-ditretbutyl cinnamic acid, the activity of aconitase was higher compared to rats that were administered with succinic, coumaric, coffee, synapic and ferulic acids by 2.47 ( p < 0.05), 2.49 ( p < 0.05), 3.44 ( p < 0.05), 2.59 ( p < 0.05) and 1.9 ( p < 0.05) times, respectively. Conclusion. The administration of the studied in this work cinnamic acid derivatives helps to restore the activity of citrate synthase, aconitase, and α-ketoglutarate dehydrogenase in rats under conditions of cerebral ischemia. The most pronounced changes in the activity of enzymes were obtained with the iadministration of 4-hydroxy-3,5-ditretbutyl cinnamic acid.

The aim of the study was to evaluate experimentally, the myoprotective effect of new chromone-3-aldehyde derivatives in conditions of muscular dysfunction and to establish a potential mechanism of myoprotective activity – the blockade of the function of sirutin 2. Materials and methods. The effect of new chromone-3-aldehyde derivatives on the development of muscular dysfunction under the conditions of an electromiostimulation test, was studied. The degree of muscle fatigue was evaluated in the «grip-strength» and through test biochemical assays (determination of the activity of lactate dehydrogenase, creatine kinase, concentration of lactic and pyruvic acids, creatinine, myoglobin, and total protein) to determine the possible mechanism of action of the test compounds (5 new derivatives of chromone-3-aldehyde) and their effect on the function of sirtuin 2 was evaluated. Results. The study showed that chromone-3-aldehyde derivatives have a pronounced myoprotective effect associated with low toxicity (class 5 toxicity according to the GHS classification), which was confirmed by the results of the «grip-strength» test and biochemical tests data. Test compounds under the X3AC1, X3AOAC and X3AN codes evince sirtuin 2 inhibitory activity, which was reflected in a decrease in its concentration by 63.6% (p Conclusion. The study showed that chromone-3-aldehyde derivatives are promising subjects for further study with the goal of creating a drug with a high myoprotective effect and an optimal safety profile.

The reaction of 3-formylchromones and 4-((2-aminophenyl)imino)-2,6-di‑tert-butylcyclohexa-2,5-dienone gave a series of N-substituted benzimidazole derivatives, characterized by 1H and 13C NMR spectroscopy, mass spectrometry and elemental analysis. The molecular structures of compounds 1 and 4 were determined by single crystal X-ray diffraction studies. Compounds 1–8 exhibit cytotoxic activity against human colon cancer cells HCT116 and breast cancer cells MCF7 at submicromolar concentrations. Compound 6 is more active against tumor cells than non-malignant fibroblasts. Compounds 1, 3, 5 and 7 exhibit antioxidant activity comparable to the reference drug Trolox.

Synthetic derivatives of flavonoids are a promising class of biologically active compounds. Here we report a family of (chromon-3-yl)-bis(3,5-dimethylpyrazol-1-yl)methanes bearing various substituents in chromone fragment. They have been studied for the antioxidant activity and spectra of their biological activity have been predicted. New Ni(II), Co(II) and Pd(II) complexes, supported by 3-[bis(3,5-dimethylpyrazol-1-yl)methyl]-6-fluoro-chromen-4-one, have been synthesized and characterized using 1H NMR, high-resolution MALDI-TOF spectrometry and elemental analyses. The molecular structures of 3-[bis(3,5-dimethylpyrazol-1-yl)methyl]-chromen-4-one 1, 3-[bis(3,5-dimethylpyrazol-1-yl)methyl]-6‑chloro-chromen-4-one 7 and Co dichloride complex with 3-[bis(3,5-dimethylpyrazol-1-yl)methyl]-6-fluoro-chromen-4-one 15 have been determined using single crystal X-ray diffraction studies. The cytotoxic activity of metal complexes and the ligand 1 has been studied on 4 cell lines of different histological origin. It has been observed that Ni complex exhibits higher cytotoxicity against breast cancer cells MCF7 and Co complex has almost the same effect on the growth of all studied tumor cells.

Background and objectives: To evaluate the effect of a new pyrimidine derivative on the change of mitochondrial function in experimental chronic traumatic encephalopathy. Materials and methods: The study was performed on male mice of the BALB/c line (acute toxicity was assessed) and male rats of the Wistar line, which were modeled chronic traumatic encephalopathy by the method of free fall of the load (weight 150 g from a 50 cm height). The injury to rats was reproduced once a day for 7 days. Further, cognitive functions, changes in sensorimotor deficiency, cerebral blood flow, neuron-specific enolase(NSE), S100&beta, glial fibrillary acidic protein (GFAP) (in blood serum) and &beta, amyloid, adenosine triphosphate (ATP) (in brain tissue supernatant) were evaluated. Mitochondrial respiration was also measured. Choline alfoscerate (100 mg/kg) was used as a reference drug. Results: The study found that the use of a new pyrimidine derivative contributed to the preservation of the mitochondrial respirometric function and cognitive functions in rats. In addition, against the administration of test-object marked increase in the concentration of ATP, the velocity of cerebral blood flow was 4.2 times (p &lt, 0.05) and 35.6% (p &lt, 0.05), respectively, as well as reduced concentration and GFAP, NSE, S100&beta, &beta, amyloid and sensorimotor deficit at 2.7 (p &lt, 0.05) times, 2 times (p &lt, 0.05), 2.4 times (p &lt, of 30.4% (p &lt, 0.05 and 46.5% (p &lt, 0.05), respectively. The LD50 (per os) for the test-object was 4973.56 &plusmn, 573.72 mg/kg. Conclusion: Based on the obtained data, high therapeutic efficacy and low systemic toxicity of the application are assumed 4-{2-[2-(3,4-dimethoxyphenyl)-vinyl]-6-ethyl-4-oxo-5-phenyl-4H-pyrimidine-1-Il}benzsulfamide in chronic traumatic encephalopathy.

To date, stress is a common medical and socially significant disease that requires rational pharmacotherapeutic correction. The anti-stress properties of ethnolic and aqueous extracts obtained from leaves of Ribes nigrum L., inflorescences of Gaillardia pulchella Foug., stems of Lysimachia punctata L were studied in this work. Acute stress was modeled by immobilization of rats for 2 hours. The test-extracts were administered per os prophylactically in a dose of 1/20 of LD 50 (2000 mg/kg). The following parameters were evaluated: organs mass coefficient (adrenal glands, thymus, spleen), the number of stomach erosion; the biochemical changes in the blood serum (adrenaline, cortisol, total protein and glucose concentration); the mitochondrial function parameters in brain and myocardium (evaluation of mitochondrial pore transitional permeability opening and mitochondrial membrane potential). 70% ethanol extract from Gaillardia pulchella Foug. inflorescences has the highest anti-stress activity, the course application of which contributed to the normalization of the weight index of organs, a decrease in glucose concentration by 64.5% (p

Conducted research devoted to the study of potential mechanisms of action implementation endotelioproteсtion 4-hydroxy- 3,5-di-tretbutyl cinnamic acid in experimental conditions simulated cerebral ischemia in rats. The research found that the cerebral ischemia in rats is accompanied by the development of endothelial dysfunction, expressed in increasing the concentration of asymmetric dimethylarginine, nNOS, iNOS and PKC, as well as reducing the concentration of eNOS. Introduction of sulodexide (to a greater extent compared with thioctic acid and mexidol restores endothelial function in conditions of brain ischemia in rats. The use of 4-hydroxy-3,5-di-tretbutyl cinnamic acid helped reduce the concentration of ADMA, nNOS, iNOS and PKC on 83.9% (p >0.05), 60.6% (p >0.05), 61. 9% (p >0.05), 108.6% (p >0.05), respectively, as well as improve the content of eNOS at 114.2% (p >0.05), thereby contributing to the correction that has developed in conditions cerebral ischemia, endothelium dysfunction