Indolyl- and Pyrrolylazine Derivatives Cause the Accumulation of Heat Shock Protein Hsp70 in Sh-Sy5Y Human Neuroblastoma Cells.

The heat shock protein Hsp70 is involved in cell defense from various types of stress, including the proteotoxic stress, which occurs during the development of many neurodegenerative diseases. This work presents data on the detection of small molecules, derivatives of indolyl- and pyrrolylazines, which can activate the synthesis of Hsp70 and cause its accumulation in the cell. The toxicity level of the new Hsp70 synthesis inducers was evaluated, and the safety of these compounds was demonstrated in experiments on SH-SY5Y neuroblastoma cell line. Derivatives of indolyl- and pyrrolylazines presented in this work can be potential therapeutic agents in models of neurodegenerative diseases that should be studied in more detail.

[Investigation of Triazavirin antiviral activity against tick-borne encephalitis pathogen in cell culture].

The efficacy of Triazavirin against the tick-borne encephalitis virus was estimated in the sensitive cell culture vs. the active drug Ribavirin. In a concentration of 128 mcg/ml Triazavirin was shown active in inhibition of the tick-borne encephalitis virus reproduction (strain Sofiin) by accumulation in the SKEV cell culture.

[The antiaggregant action of 2-morpholino-5-(thienyl-2)-6-H-1,3,4-thiadiazine in in vitro and ex vivo experiments].

The influence of 2-morpholino-5-(thienyl-2)-6-H-1,3,4-thiadiazine (H-29) on the platelet aggregation has been studied in experiments on donor plasma in vitro. It is established that H-29 causes a decrease in the platelet interaction induced by ADP and arachidonic acid. The influence of H-29 on platelet aggregation was also studied in ex vivo experiments with intravenous and oral administration, and some parameters of plasmatic hemostasis were evaluated.

1,2,4-Triazoloazine derivatives as a new type of herpes simplex virus inhibitors.

A new class of inhibitors of herpes simplex virus replication was found. The compounds under study are derived from condensed 1,2,4-triazolo[5,1-c][1,2,4]triazines and 1,2,4-triazolo[1,5-a]pyrimidines, structural analogues of natural nucleic bases. Antiherpetic activity and cytotoxicity of the compounds were studied. The corresponding triphosphates of several active compounds were prepared and tested as inhibitors of DNA synthesis catalyzed by herpes simplex virus polymerase. The potential mechanism of their action is blocking of DNA dependent DNA polymerase, a key enzyme of viral replication.

[Influence of new 1,3,4-thiadiazines on platelet aggregation in vitro and ex vivo].

The influence of new original 1,3,4-thiadiazines on the human platelet aggregation in vitro was studied. All substances inhibited the platelet aggregation induced by both ADP and arachidonic acid. 1,3,4-Thiadiazines L-19, H-30 and L-37 were the most effective inhibitors. Effect of the intravenous injection of L-19 in various doses on platelet aggregation and some parameters of plasmatic hemostasis were studied ex vivo.

[Antiaggregant properties of new 1,3,4-thiadiazine derivatives].

A series of new 1,3,4-thiadiazine derivatives have been synthesized and their effect on the human platelet aggregation in vitro has been studied. All the tested substances inhibit the human platelet aggregation induced by ADP and arachidonic acid in a broad concentration range. The most active 1,3,4-thiadiazines (L-19, L-28 and L-31) effectively inhibit platelet aggregation at concentrations within 0.01-1 mM.

[The estimation of the perspectives of the 1,3,4-thiadiazine derivatives as the protectors means for the health tissues under radiation therapy of malignant tumour patients].

We generalized the results of our own researches of the mechanisms, determined the high (90% BALB-line mice were survived) radioprotection activity by 1,3,4-thiadiazine derivatives. It was determined that this preparat achieves the highest concentrations in the critical for the acute radiation influence tissues. The preparate bind with the cell's membranes, nucleus and mitochondries, blockade the development of the radial reactions on the tissues level. Small quantity passes to the brain marrow, takes part in the regulative processes, which central nervous system is produced, reduces the metabolitical processes in the organism. It doesn't possess the election accumulation in the tumour and it is perspective for the prevention of damage health tissues under irradiation cancroid's therapy.

[Radiation protective agents effective in a wide range of radiation dosages]. / Protivoluchevye preparaty, éffektivnye v bol'shom diapazone doz oblucheniia.

Perspective chemical classes of prophylactic radioprotecting compounds were found from analysis of proper experimental data. Preparations effective in a wide range of radiation doses of various intensity were synthesized. Their activity are due to combination of antiradiation and many other pharmacological properties. During acute radiation these preparations protect stem cells pul of critical tissues but under prolonged radiation they normalize the hematological, immune and lipid peroxide oxidation systems. There is no strong correlation between radioprotection and increasing of functional reserve of organism.

[The mechanisms of the action of radioprotectors of different chemical classes in the intestinal syndrome]. / O nekotorykh mekhanizmakh deistviia radioprotektorov raznykh khimicheskikh klassov pri kishechnom sindrome.

Some thiazole, triazole, thiadiazine, and heterylalkane derivatives increased the lifespan of gamma-irradiated (9-14 Gy) mice up to 6-22 days (as opposed to 4.1 days in the irradiated control). The efficacy of chemical agents within the dose range mentioned above was mainly associated with protecting intestinal epithelium stem cells the number of which was 4-9 times as large as that of nontreated animals. There was a moderate (40-50%) decrease in oxygen consumption under the effect of the most active radioprotectors.

[Radioprotective activity of aminoarylthiazoles and various mechanisms of action]. / Radiozashchitnaia aktivnost' aminoariltiazolov i nekotorye mekhanizmy ikh deistviia.

The amino group is shown to be the reaction center that is primarily responsible for the radioprotective effect of the thiazoles under study. A phenyl residue also contributes to the radioprotective effect. The influence of thiazoles on DNA biosynthesis on radiosensitive tissues plays an important role in the biochemical mechanism of their radioprotective action.

[Antisilicotic action and side effects of polypyridylethyl-methacrylate iodomethylate]. / O protivosilikoticheskom i pobochnom deistvii iodmetilata polipiridilétilmetakrilata.

Antisilicotic and side effects of a new polymer synthetized on the basis of polymethacrylic acid were studied. The polymer not only inhibited the development of silicotic sclerosis but also induced its partial reverse development. As regards the effect intensity it appeared to be equal to highly effective polyvinylpyridine-N-oxide. The data obtained indicate the necessity of a further study of the new antisilicotic polymer with a purpose of recommending it for clinical trials.