scholarly journals КОМП’ЮТЕРНЕ ПРОГНОЗУВАННЯ ГОСТРОЇ ТОКСИЧНОСТІ ПОХІДНИХ 5-ФЕНЕТИЛ-4-R-3-ТІО(АМІНО)-1,2,4-ТРІАЗОЛУ ЗАВДЯКИ GUSAR-ONLINE ПРОГНОЗА

2020 ◽  
Author(s):  
Frolova Yu. S. ◽  
Ignatova T. V. ◽  
Kaplaushenko A. H.
Keyword(s):  
Acute Toxicity ◽  
Lethal Dose ◽  
Online Version ◽  
Toxic Substances ◽  
Computer Prediction ◽  
Triazole Derivatives ◽  
Structural Formulas ◽  
Online Prediction ◽  
Low Toxic ◽  
Derivatives Of

An important step in the development of a new drug is the prediction of its toxicity by computer screening using the program GUSAR-online. The purpose of this work is an online prediction of acute toxicity among new derivatives of 5-phenethyl-4-R-3-thio(amino) 1,2,4-triazoles. Computer prediction of acute toxicity of 5-phenethyl-4-R-3-thio(amino)- 1,2,4-triazole derivatives was performed according to the structural formulas of the compounds in the online version of the GUSAR-online program.GUSAR-online prediction for 5-phenethyl-4-R-3-thio(amino)-1,2,4- triazole derivatives was performed during the research. It was found that the average lethal dose of LD50 is from 56.1 to 2396.0 mg / kg. Based on this, all compounds are low-toxic and virtually non-toxic substances.

scholarly journals Synthesis, physico-chemical properties of 3-thio and 3-thio -4-amino derivatives of 1,2,4-triazole

2019 ◽  
pp. 28-44
Author(s):  
V. V. Parchenko
Keyword(s):  
Chemical Properties ◽  
Biological Properties ◽  
Modern Medicine ◽  
Toxic Substances ◽  
Triazole Derivatives ◽  
Synthetic Drugs ◽  
Physico Chemical ◽  
Methods Of Synthesis ◽  
Amino Derivatives ◽  
Derivatives Of

Modern medicine and pharmacy has at its disposal highly efficient synthetic drugs. Large extent of these drugs accounted for derivatives of 1,2,4-triazole. The purpose of the work was an attempt to summarize the literature in recent years related to the methods of synthesis and study of physico-chemical properties 3-thio- and 3-thio-4-amino derivatives of 1,2,4-triazole. Studies national scientists in recent years indicates prospects of the search in this direction, since this class of organic compounds is interest not only to scientists pharmaceutical, medical and veterinary field, but also among researchers of engineering, metallurgical and agricultural areas. 1,2,4-triazole derivatives are also widely used in practice for optical materials, photosensitizers are used as coloring agents, antioxidants, additives for fuels and oils, some of which are widely used as corrosion inhibitors for controlling various pests in agriculture. In addition, 1,2,4-triazole derivatives belong to the class low toxic or essentially non-toxic substances. The presence of a growing number of publications about methods of synthesis, reactions, physico-chemical and biological properties of 1,2,4-triazole, inspires scientists around the world search for perspective molecules of substituted 1,2,4-triazole. It should be noted that in spite of a sufficient amount of information about the derivatives of 1,2,4-triazole, some issues related to the generalization of data in the literature synthesis presented insufficient.

scholarly journals GRAMIN AND ITS TOXICOLOGICAL ASSESSMENT

2021 ◽  
Vol 245 (1) ◽  
pp. 50-55
Author(s):  
A.A. Ivanovskiy ◽  
◽  
E.Yu. Timkina ◽  
◽  
Keyword(s):  
Acute Toxicity ◽  
Toxicity Test ◽  
Lethal Dose ◽  
Toxic Substance ◽  
Behavioral Responses ◽  
Laboratory Mice ◽  
Subchronic Toxicity ◽  
Toxicological Assessment ◽  
Low Toxic ◽  
Student’S T

The aim of the research was to study the acute and subchronic toxicity of the drug gramine in white mice. The micromycete Drechslera graminea served as the basis for the creation of the gra-mine preparation. Experiments to determine the acute toxicity of the preparation gramine were car-ried out on outbred white mice (males) weighing 18-20 grams. The drug was administered to ani-mals intraperitoneally, once in doses from 400 to 2400 mg/kg. 6 mice were used for each dose. The condition of the animals was monitored for 14 days. The dose causing the death of 50 % of the an-imals (LD50) and the absolutely lethal dose (LD100) were determined. LD50 was calculated by the Kerber method. The study of subchronic toxicity of gramine was carried out for 30 days. The drug was administered to 10 mice intramuscularly daily, in the first 4 days, gramine was injected at a dose of 0.1 LD50, and then every 4 days the dose was increased 1.5 times and finally it was 1520 mg/kg. To determine the cumulative properties of the drug in white mice, a "subchronic toxicity" test was used. The reliability of the results obtained was taken into account in accordance with the Student's t-criterion at P <0.05. As a result, it was found that the average lethal dose (LD 50) of gramine for white mice is 1334 mg/kg, LD 100 - 2400 mg/kg. Studies of the subchronic toxicity of gramine showed that doses of the drug from 133 to 450 mg/kg did not cause significant changes in the behavioral responses of laboratory mice, and a pronounced toxigenic effect began to appear at a dose of 675 mg/kg and continued to increase after a further increase in doses of gramine (1013-1520 mg/kg), while causing mortality reaching the level of 50 %. It was found that gramine with intraperi-toneal administration of the LD50 of gramine for white mice corresponds to 1334 mg/kg, which al-lows the drug to be classified as a low-toxic substance. The cumulation coefficient of gramine is 1.14, which corresponds to the group of drugs with pronounced cumulation.

scholarly journals Determination of the parameters of acute toxicity of «Brovermectin-granulate» on earlings carp

2017 ◽  
Vol 19 (74) ◽  
pp. 20-23
Author(s):  
Yu. V. Loboiko ◽  
M. M. Danko ◽  
O. V. Krushelnytska ◽  
S. I. Kravets
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Oral Administration ◽  
General Condition ◽  
Lethal Dose ◽  
Toxic Substances ◽  
Starch Solution ◽  
Method Of Calculation ◽  
Anterior Intestine

The paper presents the results of research to determine the parameters of acute toxicity of «Brovermectin-granulate». The material for the study of acute toxicity were of carp earlings. In experiment used drug «Brovermectin-granulate» (1 g of the drug contains: active actiion substance ivermectin – 3.5 mg, tocopherol acetate – 20 mg). The introduction of the drug  was carried out orally using a probe in anterior intestine of fish. The drug was administered to fish in the form of a homogeneous suspension produced 1 % starch solution individually, in doses of 1000, 4000, 8000, 12000, 16000 and 20000 mg/kg of body weight. For settings acute toxicity determined the general condition and death of fish; for a dose of the drug (DL50) calculated by methods G. Kerber, H. Pershyn, least squares analysis of probit mortality curves for V.B. Prozorovskyj, means three points for B.M. Shtabskyj. At this stage of research it was found lethal (DL100) and maximum tolerated (DL0) dose of «Brovermectin-granulate» for earlings carp. As a result of studies found that 100% death of fish following the dose of 20000 mg/kg (DL100), and for the drug at a dose of 4000 mg/kg (DL0) set to survival of 100% fish. Established that the value of average lethal dose of «Brovermectin-granulate» for fish regardless of the method of calculation mainly coincided and were 10932,8–11200 mg/kg for earlings carp. Thus, the drug «Brovermectin-granulate» for oral administration to fish belongs to grade 4 toxicity – low toxic substances.

ACUTE TOXICITY OF OCTENIDINE HEXAFLUOROSILICATE

2021 ◽  
Author(s):  
I. O. Shyshkin ◽  
V. Yu. Anisimov ◽  
A. V. Nikitin ◽  
V. O. Gelmboldt
Keyword(s):  
Acute Toxicity ◽  
Oral Administration ◽  
Least Squares Method ◽  
Lethal Dose ◽  
Statistical Processing ◽  
Toxic Substances ◽  
White Rats ◽  
Relative Safety ◽  
Lethal Doses

The aim of the work. Determination of toxicometric characteristics of octenidine hexafluorosilicate (OHFS), characterized by significant pharmaceutical potential, in an acute experiment on rats by oral administration. Materials and Methods. A study of the acute toxicity of octenidine hexafluorosilicate was carry out on 42 male Wistar rats weighing 180–200 grams. The main criterion for quantifying the toxicity of octenidine hexafluorosilicate was LD50, which was determined using the least squares method. In addition, the following hazard indicators were calculated: 1/LD50 – median lethal dose (absolute toxicity), LD84/LD16 – the range of lethal doses (zone of acute toxic effect), 1/(LD50-S) – the total toxicity index and the S-function angle of inclination (variability of lethal doses). Statistical processing of the results was carry out using the «StatPlus 2009» software (AnalystSoft, USA, 2009). Results and Discussion. The results of the acute toxicity determination of octenidine hexafluorosilicate show that this compound, in the oral route of administration, belongs to the III class of toxicity for the human (slightly hazardous) and to the IV class of toxicity for the animals (white rats). Based on the variability of lethal doses, the studied hexafluorosilicate can be attribute to compounds that do not pose a high potential risk of the onset and development of poisoning. The calculated toxicity and hazard values of octenidine hexafluorosilicate show that it does not pose a particular danger to humans. Extrapolation to humans of acute toxicity parameters obtained in animals was determined using the coefficient of resistance to the species and is 132.15 mg/kg body weight. Conclusions. The results of determining the toxicometric characteristics of octenidine hexafluorosilicate in rats by oral administration allow to classify this compound as moderately toxic substances (LD50 = 555.05 mg / kg, toxicity class IV). The determined parameter of acute toxicity of OHFS is close to the LD50 values of other hexafluorosilicates known from the literature; relative safety and high caries-prophylactic and periodontal-protective efficacies of OHFS indicate the prospects for further studies of this compound.

scholarly journals Identifying possible target of action of 4,4a-dihydroxanthones in bacterial cells

2021 ◽  
Vol 98 (5) ◽  
pp. 558-566
Author(s):  
V. V. Frolova ◽  
N. M. Chernov ◽  
D. Yu. Ivkin ◽  
A. M. Rumyantsev ◽  
S. V. Gurina
Keyword(s):  
Antimicrobial Activity ◽  
Protein Synthesis ◽  
Acute Toxicity ◽  
Mechanism Of Action ◽  
Plasmid Dna ◽  
Cytoplasmic Membrane ◽  
Lethal Dose ◽  
Bacterial Cells ◽  
Bacterial Dna ◽  
Derivatives Of

Introduction. Partially hydrogenated derivatives of xanthone, dihydroxanthones, are being intensively studied. They are of interest due to their antimicrobial, antitumor, and antioxidant effects. Many researches are focused on the study of the cytotoxicity of dihydroxanthones and very little information is available on their antimicrobial activity. Therefore, the study of the antimicrobial activity and mechanism of action of new synthetic derivatives of 4,4a-dihydroxanthone is relevant. Preliminary studies have demonstrated that 4,4a-dihydroxanthones are active against gram-positive bacteria and have a pronounced anti-staphylococcal effect. Namely, 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone (BDC-DX) was shown to be the most active derivative.Aim of the study was to determine the possible target of action of the active derivative of BDC-DX in bacterial cells and its acute toxicity.Materials and methods. The method of measuring the intensity of absorption of the crystal violet dye by bacteria cells was used to prove the effect of BDC-DX on the permeability of the cytoplasmic membrane in bacterial cells. The plasma coagulase activity of Staphylococcus aureus was tested under the action of dihydroxanthone to determine the effect of dihydroxanthone on the process of protein synthesis. Plasmid DNA digestion method was used to study the effect of the compound on bacterial DNA. The acute toxicity of BDC-DX was determined by the express method of V.B. Prozorovsky.Results and discussion. BDC-DX increased the permeability of the cytoplasmic membrane of S. aureus. Dihydroxanthone did not directly affect the plasma coagulase activity of Staphylococcus and showed a weak damaging effect on bacterial DNA. The compound induced breaks in plasmid DNA at a very high concentration — 1 mM or 384 pg/ml and higher. BDC-DX is a low-toxic compound (the average lethal dose for oral administration of the compound is 1710 ± 170 mg/kg, the average lethal dose for intraperitoneal administration of the compound is 116.9 ± 13.3 mg/kg).Conclusion. For the first time, in-depth study of the possible mechanism of action of a new synthetic biologically active compound from the group of 4,4a- dihydroxanthones, BDC-DX, was conducted. A likely target of 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone in S. aureus cells is the cytoplasmic membrane. BDC-DX did not affect the process of protein synthesis, namely the activity of the plasma coagulase enzyme. The compound had no pronounced damaging effect on bacterial DNA. It was found that 4,4a-dihydroxanthone refers to low-toxic compounds.

scholarly journals Research of acute toxicity and the effect of detergent-disinfectant “Argomol” on the culture of ciliates Tetrahymena pyriformis

2020 ◽  
Vol 22 (4) ◽  
pp. 22-26
Author(s):  
D. A. Zasiekin ◽  
◽  
A. G. Pushkova ◽  
R. O. Dymko ◽  
◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Guanidine Hydrochloride ◽  
Lethal Dose ◽  
Tetrahymena Pyriformis ◽  
Intragastric Administration ◽  
Toxicological Studies ◽  
Wide Range ◽  
Low Toxic ◽  
Dairy Equipment

Detergents and disinfectants for sanitation of milking equipment and dairy equipment must have a wide range of antimicrobial activity and provide a proper cleaning effect. At the same time, they must meet high standards of environmental safety and non-toxicity. The article presents data on the parameters of acute toxicity of the new detergent-disinfectant “Argomol”, based on lactic acid, “Katamine AB”, polyhexamethylene guanidine hydrochloride and colloidal silver solution, as well as the toxicity of the tool, which was determined using the express method of Tetrachymena pyriformis. The acute toxicity of the means and its working 0.5% solution in tentative and detailed experiments on white mice was determined and the median lethal dose (DL50) was determined by the method of G. Kerber. It was found that the DL50 of the means in white mice for intragastric administration when calculated by the method of G. Kerber is 4250 mg/kg body weight, and 0.5% of its solution — more than 11000 mg/kg body weight, i. e. according to SOU 85.2-37-736:2011 “Veterinary drugs. Determination of acute toxicity”, this indicates that the means belongs to the IV class of toxicity, which combines low-toxic substances. The results of research on the effect of the new detergent-disinfectant “Argomol” on the culture of ciliates Tetrahymena pyriformis are presented. It was found that the detergent-disinfectant “Argomol” in concentrations of 0.02–0.5% at exposures of 1–10 min did not show toxic effects on the ciliate Tetrahymena pyriformis. Toxicological studies on ciliates suggest that the detergent-disinfectant “Argomol”, when used in the recommended doses and exposures, can be used for sanitation of milking equipment and dairy equipment, as it is environmentally friendly and low-toxic.

scholarly journals Acute Toxicity of Organotin on Fresh Water Shrimps and its Resistance by Marine Bacteria

2021 ◽  
Vol 1 (2) ◽  
pp. 6-13
Keyword(s):  
Acute Toxicity ◽  
Fresh Water ◽  
Marine Bacteria ◽  
Marine Ecosystem ◽  
Lethal Dose ◽  
Viable Count ◽  
Resistant Bacteria ◽  
Toxic Substances ◽  
Tributyltin Chloride ◽  
Significant Difference

Abstract: This present study was aimed at investigating the acute toxicity of organotin on fresh water shrimps and its resistance to marine bacteria. 200 water shrimps were exposed to varying concentrations of Tributyltin Chloride (TBTCL) and Diphenyltin Chloride (DPTCL) for 96 hours and a probit was used to determine the lethal dose (LD50). 200g of sediment from Onne sea port Rivers State was manually polluted by TBTCL and DPTCL for 56 days. Organotin resistant bacteria were screened on mineral salt medium at different concentration of the organotin using the spread plate technique. Results from this study showed a lethal doze (LD50) of 4.24mg/l after 24 hours and 1.97mg/l after 48 hours for TBTCl on fresh water shrimps and a lethal doze of 21.05mg/l after 24 hours, 0.83mg/l after 48 hours and 0.006mg/l after 72 hours for DPTCl. The total viable count of bacteria obtained from varying concentrations of TBTCl indicates that approximately 65% of bacterial populations were resistant to 3.0mM of TBTCl and DPTCI since these isolates could grow on MSA supplemented with TBTCI and DPTCI. Statistically, there was no significant difference between the bacterial loads between the different concentrations of TBTCL. Acute toxicity effect of TBTCl and DPTCl on fresh water shrimps reveals TBTCl and DPTCl as one of the toxic substances in the marine ecosystem however; marine bacteria can be harnessed for their resistant abilities.

Acute toxicity of an insecticidal little containing ivermectin and fipronil for white mice

2020 ◽  
pp. 31-32
Author(s):  
Mikhail A. Levchenko ◽  
◽  
Natalia A. Sennikova ◽  
Keyword(s):  
Acute Toxicity ◽  
Lethal Dose ◽  
Live Weight ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Toxicological Assessment ◽  
Russian Research Institute ◽  
Veterinary Entomology ◽  
Russian Research

Toxicological assessment is a mandatory research step in the development of new insecticidal drugs. At the All-Russian Research Institute of Veterinary Entomology and Arachnology, a prototype of the insecticidal bait Mukhnet IF was obtained with an active ingredient content of 0.06% ivermectin and 0.015% fipronil, which showed a highly effective effect against houseflies. This work presents the results of the study of acute oral toxicity of the above agent. For this, male white mice with a live weight of 16-26 g were selected. They were kept on a starvation diet for one day in individual houses with water. The drug was given in mg/kg body weight the next day. A total of 33 doses have been tested, ranging from 100 mg/kg to 40,000 mg/kg. The animals were observed for 14 days. According to the research results, it was revealed that at doses up to 20,000 mg/kg there were no signs of intoxication, but when tested at 25,000 mg/kg in some mice, these signs were noted, and at 30,000, 35,000 and 40,000 mg/kg deaths were recorded 20±10, 45±30 and 60±20%, respectively. It was not possible to test the drug over the last above dose due to incomplete eaten by mice. According to the degree of danger for warm-blooded animals, the drug belongs to the 4th class of low-hazard drugs (average lethal dose of 5000 mg/kg or more) in accordance with the classification of GOST 12.1.007-76. When analyzing the literature data on the toxicological characteristics of preparations containing ivermectin and chlorfenapyr, it was revealed that the insecticidal agent in its acute toxicity for warm-blooded animals is comparable to known analogues.

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

2020 ◽  
Vol 20 (10) ◽  
pp. 1241-1249
Author(s):  
Hong-Chuan Liu ◽  
Li-Ming Qiao ◽  
Wei Zheng ◽  
Zhao-Bao Xiang ◽  
Hai-Sheng Chen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Folk Medicine ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

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