Synthesis of Glycyrrhizic Acid Conjugates with Amino-Acid Methyl Esters and their Ability to Stimulate Antibody Genesis in Mice.

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.

Effects of novel hexahydropyrimidine derivatives as potential ligands of M1 muscarinic acetylcholine receptor on cognitive function, hypoxia-induced lethality, and oxidative stress in rodents.

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 1а and 1е 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.

Nootropic Activity of a Novel (-)-Cytisine Derivative (3aR,4S,8S,12R, 12aS,12bR)-10-Methyl-2-Phenyloctahydro-1H-4,12a-Etheno-8,12-Methanopyrrolo[3',4':3,4]Pyrido[1,2-a] [1,5]Diazocine-1,3,5(4H)-Trione.

We performed screening of nootropic properties of 10 new derivatives of quinolizidine alkaloid (-)-cytisine. Compounds with ß-endo stereochemistry were more active than α-endo-isomers. Under stress conditions (3aR,4S,8S,12R,12aS,12bR)-10-methyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3',4':3,4]pyrido[1,2-a] [1,5]diazocine-1,3,5(4H)-trione enhanced memory and had a positive effect on cognitive functions of rats. According to molecular docking data, the nootropic activity of the compound can be associated with its affinity for the glutamate-binding subunits GluK1 and GluR2 of the kainate and AMPA receptor, respectively.

[Abortifacient properties and effect of an misoprostol analogue 11-deoxy-misoprostol on the contractile activity of the rat uterus].

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.

Choleretic activity of 2-demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol on the model of CCl4-induced hepatitis.

Therapeutic administration of 11-deoxymisoprostol had a hepatoprotective effect, which manifested in a decrease in the content of alanine transaminase and aspartate transaminase in blood plasma, and produced a choleretic effect in rats with CCI4-induced toxic hepatitis.

[Hepatoprotective effect of 2-demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol].

2-Demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol (11-DMP) produces antioxidant effect on the models of toxic hepatitis induced by paracetamol and carbon tetrachloride. The drug normalizes the lipid peroxidation (LPO) prosess in rat liver of the rat and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the rat blood, thus demonstrating hepatoprotective action.

[Some aspects of the antiarrhythmic effect of glialin].

The antiarrhythmic activity of allapinine and glialin (a complex of allapinin and glycyrrhizic acid) was studied on models of arrhythmias induced in rats and guinea pigs by intravenous administration of calcium chloride, aconitine, barium chloride, and strophanthin. The antiarrhythmic activity of glialin is qualitatively analogous to that of allapinine. The advantage of glialin over allapinin is its low toxicity, which is due to the presence of glycyrrhizic acid.

Gastroprotective properties of 11-deoxymisoprostol (prostaglandin E1 analog) and its effect on the level of sialic acids in gastric tissue of rats with peptic ulcer.

11-Deoxymisoprostol (prostaglandin E1 analog) exhibited a pronounced gastroprotective effect on various models of experimental ulcers induced by nonsteroid antiinflammatory drugs. A relationship between high resistance of the gastroduodenal mucosa under the effect of 11-deoxymisoprostol and changes in the level of sialic acid was detected.

[Study of pharmacological properties of betulin bishemiphthalate]. / Issledovanie nekotorykh farmakologicheskikh svoistv bisgemiftalata betulina.

The results of pharmacological tests showed that betulin bishemiphthalate possesses hepatoprotector, antioxidant, and immunotropic properties. Administered in combination with hydroxymethyluracil, that betulin bishemiphthalate prevented the loss of experimental animals upon irradiation.

[Pharmacological properties of 11-deoxymisoprostol]. / Farmakologicheskie svoistva 11-dezoksimizoprostola.

11-Deoxymisoprostol showed gastroprotector activity on the acute models of ulcers induced by acetylsalicylic acid and ethanol and produced curative effect on the chronic ulceration model induced by acetic acid. The positive effect is manifested by a decrease in the number of destructions and in the total area of chronic damage in the mucous membrane of the stomach. In addition, 11-deoxymisoprostol showed antiphlogistic activity on the acute edema models induced by carrageenan and formalin, by decreasing the model foot edema growth in experimental animals. The drug also decreased the level of lipid peroxidation in the rat blood serum on the background of acute ethanol ulceration.

[Synthesis and pharmacological activity of betulin dinicotinate]. / Sintez i farmakologicheskaia aktivnost' dinikotinata betulina.

The assignment of NMR resonances of lupane triterpenoids was refined by the example of 3,28-dinicotinoylbetulin, obtained by acylation of betulin. Hepatoprotective, untiulcer, antiinflammatory, reparative, and anti-HIV activities were found for the compound. In addition, it was demonstrated to have immunomodulatory activity, for the first time detected among lupane triterpenoids. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 6; see also http://www.maik.ru.

[Pyrimidine derivatives increase antibiotic therapy efficacy after ionizing irradiation]. / Proizvodnye pirimidina povyshaiut éffektivnost' antibiotikoterapii pri ioniziruiushchem obluchenii.

Pyrimidine derivatives increased the antibiotic therapy efficacy in albino rats irradiated with RUM-7 apparatus for close-focus roentgenotherapy. 2-Methyl-4-amino-6-oxypyrimidine was twice as efficient as oxymethyluracil and 6 times as efficient as methyluracil in the stimulation of the skin reparative regeneration. When the total irradiation was performed with LUCH-1 apparatus in a dose of 6 Gy the pyrimidine derivatives also increased the antibiotic therapy efficacy. After the prophylactic use of the pyrimidine derivatives for 7 days prior to the total irradiation their therapeutic effect increased, the level of the exudative component lowered, the tissue epithelization increased, the terms of the wound healing decreased and the animal lifespan increased.