A 1:4 inclusion complex of 11-deoxymisoprostol (II) with glycyrrhizic acid (complex III) was synthesized and exhibited high anti-ulcer activity in experimental models of gastric mucosal ulcers (GMUs) inWistar rats induced by indomethacin and diclofenac. Complex III at a dose of 1 mg/kg (0.1 mg of II) reduced the number of indomethacin gastric ulcers by 46.4% (p < 0.012) as compared with the control group and by 39.2% as compared with II at the same dose. The anti-ulcer activity of complex III at a dose of 1 mg/kg was 5.8 times higher than that of the initial prostaglandin at an equivalent dose (0.1 mg/kg) in a model of gastric ulcers caused by diclofenac.

Conjugates of glycyrrhizic acid (GA) with methyl esters of L-amino acids (valine, methionine, and glutamic acid) containing the amino-acid residues in the carbohydrate moiety of the glycoside were synthesized using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The resulting GA conjugates at a dose of 2 mg/kg stimulated a primary immune response (production of antibody-forming cells, AFCs) in outbred mice by 1.6 - 3 times as compared with the control. The conjugate of GA with Glu(OMe)2 stimulated antibody genesis in outbred mice 1.7 times more efficiently than N-acetylmuramyl dipeptide and showed a stimulating effect on AFC production in the spleen of CBA mice.

The hypoglycemic activity of glycyrrhizic acid (GA, I), its trisodium (II) and sodium-dilithium salts (III), and a conjugate with L-methionine methyl ester (IV) was studied using an alloxan diabetes model after peroral administration to male Wistar rats. It was found that GA and its conjugate IV at a dose of 100 mg/kg exhibited hypoglycemic activity and reduced the blood glucose content of the animals by 35.5 and 42.6%, respectively, after 120 min. GA conjugate IV had low toxicity and hypoglycemic activity superior to those of GA and acarbose.

Изучена гипогликемическая активность глицирризиновой кислоты (ГК) (I) и ее производных — тринатриевой (II), натрий-дилитиевой (III) солей и конъюгата с метиловым эфиром L-метионина (IV) при пероральном введении крысам-самцам линии Вистар на модели аллоксанового диабета. Установлено, что ГК и ее конъюгат IV в дозе 100 мг/кг обладают гипогликемической активностью и снижают содержание глюкозы в крови животных на 35,5 и 42,6 %, соответственно, через 120 мин. Конъюгат ГК (IV) является малотоксичным веществом и превосходит по гипогликемической активности ГК и акарбозу.

The tetra-O-methyl ether of quercetin (QU) 3 (54%), 3,7,4′-tri-O-methyl ether 4 (30%), and a previously unreported 3,7,3-tri-O-methyl ether of QU 5 (7%) were obtained via methylation of QU by an excess of diazomethane in dioxane. Their structures were established using 2D NMR (1H–1H COSY, 1H–1H NOESY, 1H–13C HSQC, 1H–13C HMBC). Tetra-O-methyl ether of QU 3 exhibited pronounced hypoglycemic activity, reduced alloxan-induced hyperglycemia in rats by 44.5% compared to a control, and was 2.7 times more active than QU.

A conjugate of glycyrrhizic acid (GA) with L-phenylalanine methyl ester was synthesized using N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. Chemical modification of GA via addition of L-phenylalanine methyl ester moieties in the carbohydrate part of the glycoside was shown to form a marginally toxic compound with high anti-inflammatory activity in carrageenan- and formalin-induced mouse inflammation models and with pronounced antiulcer activity in rats. This was a significant advantage of this compound over known anti-inflammatory drugs.

The neurodegenerative diseases have a complex pathogenetic mechanism comprising oxidative stress and receptor system dysfunction caused by various damaging factors such as, for example, brain hypoxia. The purpose of this study was to elucidate the influence of hexahydropyrimidine derivatives on learning, memory, and orientation and locomotor activities in the passive avoidance (PA) and open field (OF) tests and to evaluate these compounds for their potential antihypoxic and antioxidant action on normobaric hypercapnic hypoxia and toxic hypoxia models. We demonstrated that compounds 1a and 1e administered as a single 100 mg/kg dose (p.o.) one hour before the tests increased the latency time to enter the dark compartment for the first time and reduced the time spent in the dark compartment on the 2nd, 7th, and 14th days of PAT and increased the number of squares crossed and hole-pokings in the OF test. It was also shown that single administration of compounds 1a and 1e (in 100 mg/kg dose, p.o.) one hour before generation of hypoxia increased the life span of mice under normobaric hypoxia by 30% (P < 0.05) and, after injection of sodium nitroprusside, they decreased the malondialdehyde (MDA) level and increased the catalase level in the brain of mice. According to molecular docking results, compounds 1a and 1e are bound in the orthosteric active site of M1 muscarinic receptor via supramolecular interactions with a number of functional amino acids. The results indicate that hexahydropyrimidine derivatives have a beneficial effect on the memory, learning processes, and orientation and locomotor activities of rats in an unfamiliar environment and exhibit antihypoxic and antioxidant activities under hypoxia in mice. The cognitive enhancement can be mediated by the effect of lead compounds on the M1 muscarinic acetylcholine receptor.

The aim - to establish the main pharmacokinetic parameters of 11-deoxyimisoprostol after intragastric administration. Materials and methods. The experiments were performed on 410 white outbred rats - females weighing 180-220 g. 11-deoxymysoprostol was administered to rats intragastrally at a dose of 2.0 mg/kg. Blood and organs were taken for examination at 6, 12, 15, 30 minutes and hourly for 12 hours after administration. After these intervals, the concentration of the drug in the blood and tissue homogenates of laboratory animals was determined, and in the urine - every hour during the day. Chromatographic separation was carried out using a liquid chromatograph (Shimadzu, Japan LC-20 PROMI- NENCE with a diode - array detector SPD-20A).Results. 11-deoxyimisoprostol is rapidly absorbed from the gastrointestinal tract. The maximum (6.625 μg/ml) of the compound in the blood plasma is reached 15 minutes after intragastric administration. When this occurs, a simultaneous in - crease in the concentration of the metabolite - 11-deoxyimisoprostolic acid. The maximum concentration (23.547 µg/ml) of the metabolite in the blood plasma is reached 30 minutes after the administration of 11-deoxyimisoprostol. 11-deoxyimisoprostol is intensively distributed throughout the organs and tissues, while the compound has the highest affinity for myometrium and liver. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. The active metabolite of 11-deoxyimisoprostol is intensively distributed in organs and tissues, while in the greatest amounts it was detected in the myometrium and the liver and kidneys. The smallest quantities of the test substance were found in the lungs, the brain, and the omentum. In the urine, 11-deoxyimisoprostolic acid is determined during the first days of the study, with a maximum clearance of 6-8 hours after administration.Conclusion. 11-deoxyimisoprostol has a short half - life after intragastric administration (T1/2=0,550 h), which indicates the absence of cumulative properties. The nature of the pharmacokinetic curve is monoexponential.

Introduction. Nootropic drugs are components of complex therapy for various neurological dysfunctions. One of the classes of ND are pyrrolidone derivatives, which, in addition to a direct effect on cognitive functions, increase the brain's resistance to hypoxia. Aim. The work was to study the effect of the 3-aminopyrrolidin-2-one derivative containing the norbornane fragment (P-11) on different memory phases in rats and to evaluate its antihypoxic properties. Materials and methods. The effect of P-11 on memory was assessed on passive avoidance test (PAT) in rats. The antihypoxic properties of P-11 were studied on a model of acute normobaric hypoxia with hypercapnia, assessing the life span of laboratory animals and the level of lipid peroxidation processes in the brain. Results and discussion. It was shown that the introduction of P-11 at different stages of the development of passive avoidance reaction improves the ability of animals to learn and extract a memorable trace of pain stimulation 24 hours after the development of a reflex. On a model of normobaric hypoxia with a single injection, P-11 showed a tendency to increase the life span of rats relative to the control, and with a 14-day treatment, pronounced antihypoxic properties were observed compared with other pyrrolidone derivatives, pyracetam and phenotropil, which manifested in an increase in life span of mice, as well as in lowering lipid peroxidation processes in brain tissue. Conclusion. Thus, it was shown that a new derivative 3-aminopyrrolidin-2-it exhibits nootropic and antihypoxic properties.

Introduction. Nootropic drugs are components of complex therapy for various neurological dysfunctions. One of the classes of ND are pyrrolidone derivatives, which, in addition to a direct effect on cognitive functions, increase the brain's resistance to hypoxia. Aim. The work was to study the effect of the 3-aminopyrrolidin-2-one derivative containing the norbornane fragment (P-11) on different memory phases in rats and to evaluate its antihypoxic properties. Materials and methods. The effect of P-11 on memory was assessed on passive avoidance test (PAT) in rats. The antihypoxic properties of P-11 were studied on a model of acute normobaric hypoxia with hypercapnia, assessing the life span of laboratory animals and the level of lipid peroxidation processes in the brain. Results and discussion. It was shown that the introduction of P-11 at different stages of the development of passive avoidance reaction improves the ability of animals to learn and extract a memorable trace of pain stimulation 24 hours after the development of a reflex. On a model of normobaric hypoxia with a single injection, P-11 showed a tendency to increase the life span of rats relative to the control, and with a 14-day treatment, pronounced antihypoxic properties were observed compared with other pyrrolidone derivatives, pyracetam and phenotropil, which manifested in an increase in life span of mice, as well as in lowering lipid peroxidation processes in brain tissue. Conclusion. Thus, it was shown that a new derivative 3-aminopyrrolidin-2-it exhibits nootropic and antihypoxic properties.

The hepatoprotective and choleretic activities of three levopimaric acid derivatives were studied experimentally using a CCl4-induced acute hepatitis model in rats. It was established that all investigated levopimaric acid derivatives tended to increase bile secretion whereas (5R,9R,13S,18S)-20-isopropyl-5,9-dimethyl-17-{[(4-methylphenyl)sulfonyl]imino}-14-oxopentacyclo[10.6.2.01, 10.04, 9.013, 18]eicosa-15,19-diene-5-carboxylic acid (I) and dimethyl (4bS,8R)-2-isopropyl-3′-4b,8-trimethyl-2′,4′-dioxo-4,4a,4b,5,6,7,8,8a,9,10-decahydro-3H-spiro[3,10a-ethanophenanthrene-11,5′-[1,3]thiazolidine]-8,12-dicarboxylate (II) reduced transaminase enzyme levels in blood serum.

Большое количество исследований, проводимых во всем мире, свидетельствует о высокой востребованности мизопростола и мифепристона в акушерстве и гинекологии, а также о продолжающемся поиске оптимальных доз мизопростола для снижения частоты побочных эффектов и выявления отдаленных последствий проведения медикаментозного аборта (МА) с использованием этих препаратов [28, 50]. В работе представлен обзор литературы по применению мизопростола и мифепристона для прерывания беременности в первом, втором и третьем триместрах по различным показаниям; сравнение эффективности данной схемы с хирургическими методами проведения аборта. Проведен анализ эффективности различных способов введения мизопростола, а также сравнение его с другими простагландинами, применяемыми для проведения МА и созревания шейки матки при подготовке к родам. Поиск литературы проведен в базах данных электронных библиотек PubMed, PMC, Elibrary.

The compositions of neutral lipids (NL) and fatty acids (FA) from subterranean parts of the introduced plants Helleborus abchasicus and H. caucasicus (Ranunculaceae) were established and compared with those of the wild species. The FA from diacyl- and triacylglycerides and free FA from these introduced species had elevated contents of unsaturated acids because of 18:2. The lipid-soluble NL constituents included 10 identified sterols, the major ones of which were cholesterol, sitosterol, and lanosterol. NL from H. abchasicus (introduced and wild) and H. caucasicus (wild) exhibited pronounced anti-inflammatory activity at the level of Voltaren and moderate wound-healing activity.

The antihypoxic activity of a series of quinopimaric acid scaffold derivatives was studied. It was shown that compounds 3 , 5 , and 8 increased the lifespan of mice in various hypoxia models.

The mnestic and antihypoxic effects of new derivatives of the quinolizidine alkaloid (−)-cytisine on acquisition of a conditioned passive avoidance reflex (CPAR) were studied in rats; effects on normobaric (jar) hypoxia were studied in mice. Screening studies showed that the benzamide and the N-(12-methylcytidin-3-yl)-N′-phenylurea not only improved learning and memory, but also increased the resistance of the brain to hypoxia.

Изучена мнестическая и противогипоксическая активность новых производных хинолизидинового алкалоида (—)-цитизина при выработке условного рефлекса пассивного избегания (УРПИ) у крыс и нормобарической (баночной) гипоксии у мышей. В результате скрининга установлено, что бензамид и N-(12-метилцитизин-3-ил)-N’-фенилмочевина не только улучшают обучение и память, но и повышают устойчивость мозга к гипоксии.

12-N-β-Hydroxyethylcytisine derivatives containing Cl, Br, and nitro groups on the 2-pyridone core were synthesized. Their antiarrhythmic activity was studied in vivo.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The neuropharmacological activity of two (–)-cytisine derivatives with adamantyl fragments was studied. It was shown that N-1-adamantylcytisine-12-thiocarbamide exhibited in tests in vivo a pronounced mnestic effect, increased the lifespan of laboratory animals under hypoxic conditions, and also enhanced in vitro binding of transcription factors NFAT and NF-κB to the DNA sequences corresponding to them.

Ethyl ether of 11-deoxy-16-hydroxy-16-metylprostaglandin E1 (11-deoxymisoprostol) increases the contractile activity of uterine horn segments isolated from nonpregnant rats and produces abortive effect when given in a period of time within 1 - 16 days of pregnancy. The drug action is related to a decrease of the progesterone level in ovarian incubates of pregnant rats.