The results of assessing the possibility of using the PASS computer system to predict biological activity by structural formula for chemical compounds as a stage in pre-experimental screening of new substances are presented below. Table 1 shows the results of predicting 14 types of biological activity in the form of values of the probability of presence (Pa) and the probability of absence of this activity (Pi).

With the studied virtual compounds in N-(β-D-galactopyranosyl)-thiosemicarbazide, antibacterial (antimycobacterial), anti-tuberculosic (antituberculosic), antiviral (antiviral (Influenza)), antitumor (antineoplastic >) activity of the compounds are predicted with a high probability (0.9 > 0.5) and with a low probability of cytotoxic/cytostatic (Cytostatic/Cytotoxic) activity. Next, we analyzed possible toxic effects with a probability Pa > 0.5 for compounds 1, 2 based on their structural formulas (Table 2).

The results of computer predictions, we found that compounds 1.2 are predicted to have increased side effects, the ability to cause hyperuricemia an increased level of uric acid in the blood. Among the studied compounds, promising substances for experimental research identified with a high probability of antibacterial activity in N-(β-D-galactopyranosyl)-thiosemicarbazide compounds (Pa/Pi 0.799/0.004 antimycobacterial).

The acute toxicity of N-(β-D-galactopyranosyl)-thiosemicarbazide was tested in the Biotechnology and Chemistry, Bacteriology Departments of Kyrgyz Republican Center for Diagnostics and Expertise. Study aim of acute toxicity was to determine tolerable, toxic and lethal doses of a pharmacological substance and cause of animals’ death [6].

When studying the toxicology of newly synthesized compounds, the first prerequisite is to determine the parameters of acute toxicity. These indicators are necessary to establish the degree of hazard of a chemical, as well as, for further research, where knowledge of the degree of acute toxicity is required.

Acute toxicity of pharmacological substances [7] [8] is determined by the following parameters: LD₀ is the maximum tolerated dose, LD₅₀ is an average lethal dose, LD₁₀₀ is minimum lethal dose [9]. LD₁₆ and LD₈₄ are also determined to establish the confidence limits of LD₅₀ the average lethal dose.

There are a number of classifications of chemical substances for the assessment of acute toxicity [10] [11] [12]. To assess the toxicity of antiparasitic drugs, the classification according to [12] [13] is more suitable. Based on the foregoing,

we studied the acute toxicity parameters of a new carbohydrate derivative of thiosemicarbazides N-(β-D-galactopyranosyl)-thiosemicarbazide.

The experiments were carried out on 36 clinically healthy white mice of both sexes with a live weight 18 to 22 grams. The substance was administered to animals orally in the form of a 10% solution using a syringe equipped with a special metal probe, in various doses. Control animals received an appropriate volume of sodium chloride saline solution.

During the experiment, the animals were not limited to feeding and watering. The experiments lasted 12 days, during which the general condition, the nature and degree of chemical toxicity, the time of death of the experimental and control mice were observed. The corpses of the dead experimental animals were subjected to a visual pathoanatomical autopsy to establish the degree and nature of organ damage and the causes of death.

Statistical processing of digital materials was carried out by the method [14], modified [15], using ordinary graph paper [16].

The results of the experiments showed that the nature and degree of chemical toxicity in white mice were in direct proportion to the doses of the studied compound. Signs of poisoning when giving large doses appeared for the first time within minutes and were often fatal within 1 to 2 hours after giving. They were mainly expressed in the manifestation of an excited state (anxiety, increased reaction to external stimuli, tachycardia, rapid breathing), from feed tons of water.

Then this condition passed on to progressive oppression, leading to complete prostration. Breathing is shallow, frequent, and intermittent. Rapid palpitations, sometimes turning into arrhythmias. The death of animals that received large toxic doses of the compound occurred mainly on the first day of administration of the substance. The surviving animals showed mild diarrhea and poor appetite, which soon subsided.

The postmortem autopsy of dead white mice revealed: the back of corpses is soiled with liquid feces; the brain is swollen, hyperemic; the mucous membrane of the stomach and intestines is strongly hyperemic, in some places there are areas of extensive hemorrhage and necrosis; the liver is enlarged, dark red in color, its parenchyma is softened; kidneys of normal size, multiple punctate hemorrhages under the membrane; the heart is flabby, the myocardium is soft, the ventricles contain dark red blood clots, there are punctate hemorrhages on the epicardium and endocardium; the lungs are swollen of a dark red color, the blood vessels are dilated.

The results of statistical processing of digital experimental data showed that (Table 3) the maximum tolerated dose (LD₅₀) of N-(β-D-galactopyranosil)-thiosemicarbazide for white mice was 400 mg/kg, LD₁₆ was 754 mg/kg, the average lethal dose LD₅₀ was 1134 (957 ± 1311) mg/kg, LD₈₄ was 1534 mg/kg and absolutely lethal dose (LD₁₀₀) was 2000 mg/kg.

The results obtained indicate that, according to the current classification of the hazard of chemotherapeutic drugs according to the degree of impact on the body (GOST 12.1.007-76), N-(β-D-galactopyranosyl)-thiosemicarbazide belongs to substances of III class of moderate hazard [17] confirms the prospects for further study of this compound in this direction.

The experiments were carried out at the Department of Biotechnology and Chemistry and at the Department of Bacteriology of the Kyrgyz Republican Center for Diagnostics and Expertise by the in vitro method using generally accepted bacteriology techniques [18] [19] [20] [21] [22].

For this, by means of serial dilutions with distilled water (1:10; 1:20; 1:40 … 1:2650), various concentrations of the substance were prepared, the bactericidal effect of which was studied by plating Salmonella infection of lambs on agar-agar in Petri dishes (Salmonellatyphimurium, 04), salmonellosis of calves (Salmonella Dublin, 09) and colipathogenic serotypes of Escherichia coli (Escherichiacoli 055, 026) and the addition of 0.1 ml of each dilution of the substance.

The results were taken into account after daily cultivation in a thermostat at t = 37˚C, by measuring the diameters of the zones (in mm), and by the absence of microorganism growth at the place where the compound was applied. Distilled water (i.e., solvent) served as a control.

The results of experiments carried out on a solid nutrient medium show (Table 4) that the test compound showed bactericidal activity against the selected microbial cultures, although no pronounced species specificity was observed in its action.

*numbers show diameter of microorganisms’ growth zones (in mm).

− lack of growth, + presence of growth.

The bacteriostatic activity of the substance was studied by diluting it in mesopatamia broth at the same concentrations as in the previous experiment, followed by sowing pure cultures in it. The results of this series of experiments showed (Table 5) that the bacteriostatic substance acts on Esch. coli 055 from a dilution of 1:380, for other cultures from a dilution of 1:640.