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PREDICTION OF BIOLOGICAL ACTIVITY AND TOXICITY OF 5-DIETHOXYPHOSPHORYL4-ETHOXY-5-ETHOXYCARBONYL-2 – (1-IMINO)ETHYLTHIO-4,5-DIHYDROTHIAZOLE AND ITS DERIVATIVES

Diyarova N.R. 1 Tovkaleva E.V. 1 Ermolaeva A.A. 1 Lavrova O.M. 1
1 Kazan National Research Technological University
1. Poroikov V.V. Computer prediction of biological activity of substances: limits of the possible. Chemistry in Russia, 1999. No. 2. P. 8-12.
2. Asadov H.A., Huseynov F.I., Mikhailov G.G., Valiullina R.J. Moscow, 2009, Chemistry of heterocyclic compounds. 2001. vol. 45. number 7. P. 878.

The biological activity of 5-Diethoxyphosphoryl-4-ethoxy-5-ethoxycarbonyl-2-(1-imino)ethylthio-4,5-dihydrothiazole was analyzed by PASS (Prediction of Activity Spectra for Substances) and toxicity by GUSAR (General Unrestricted Structure-Activity Relationships).

Methods of obtaining these substances:

1. 5-Diethoxyphosphoryl-4-ethoxy-5-ethoxycarbonyl-2 – (1-imino)ethylthio-4,5-dihydrothiazole. One solution of thiocyanate acetal (3.83 g, 0.0 l mol) and thioacetamide (0.75 g, 0.01 mol) in absolute acetonitrile or ethanol (30 ml) was heated with a reverse refrigerator for 16 hours. the solvent was removed in vacuum and 10 ml of 3:1 ether-acetone was added to the resulting oil. The yellow crystalline precipitate was filtered and dried to yield 2.31 g (56 %) of the compound.

To determine the potential biological activity chose the program PASS, which is based on the analysis of dependencies structure-activity. Pa and Pi are presented as estimates of the measure of the substance belonging to the classes of active and inactive compounds, respectively. The larger the value ofPa for a particular activity and the smaller the value ofPi, the greater the chance to detect this activity in the experiment. Forecasts of biological activity of compounds are given in table 1.

As can be seen from table 1, it can be said that both compounds exhibit different inhibitory properties.

Further, the forecast of acute toxicity of the studied compound was carried out using the software product GUSAR (General Unrestricted Structure-Activity Relationships) presented in tables 2 and 3.

1. 2.

dijr1a.wmf dijr1b.wmf

Table 1

Prediction of biological activity based on the results of the PASS program 1

1.

Pa

Pi

Activity

0,795

0,015

Mannotetraose inhibitor of 2-alpha-N-acetylglucosaminyltransferase

0,666

0,024

Supplementfactor d inhibitor

0,607

0,009

Inhibitorkokolina

0,648

0,068

Inhibitor of CDP-glycerol-glycerol phosphotransferase

0,613

0,039

An inhibitor of glutamate-5-polulegendarnaya

0,567

0,024

Inhibitor of N-acetylneuraminate 7-O (or 9-O) – acetyltransferase

0,579

0,054

Inhibitor of 5-O – (4-coumaroyl) – D-hinata 3' – monooxygenase

0,584

0,059

Sugarphosphataseinhibitor

0,503

0,004

Stimulatorofboneformation

0,507

0,020

Generalanesthesia

0,541

0,060

Treatment of acute neurological disorders

2.

Pa

Pi

Activity

0,747

0,021

Mannotetraose inhibitor of 2-alpha-N-acetylglucosaminyltransferase

0,645

0,028

Supplementfactor d inhibitor

0,598

0,032

Arginine-2-monooxygenase inhibitor

0,587

0,043

An inhibitor of glutamate-5-polulegendarnaya

0,543

0,014

Inhibitorkokolina

0,606

0,081

Inhibitor of CDP-glycerol-glycerol phosphotransferase

0,515

0,019

Generalanesthesia

0,556

0,061

Inhibitor of 5-O – (4-coumaroyl) – D-hinata 3' – monooxygenase

0,495

0,005

Paraoxonasesubstrate

0,546

0,058

Treatment of acute neurological disorders

0,525

0,048

Venomininhibitor AB

0,545

0,069

Sugarphosphataseinhibitor

0,494

0,033

Inhibitor of N-acetylneuraminate 7-O (or 9-O) – acetyltransferase

0,456

0,005

Stimulatorofboneformation

 

Table 2

Prediction of acute toxicity in rats using the GUSAR software product 1

1.

Rat IP LD50 Log10(mmol/kg)

Rat IV LD50 log10(mmol/kg)

Rat Oral LD50 log10(mmol/kg)

Rat SC LD50 log10(mmol/kg)

-0,539 in AD

-0,873 in AD

-0,024 in AD

-0,329 in AD

Rat IP LD50 (mg/kg)

Rat IV LD50 (mg/kg)

Rat Oral LD50 (mg/kg)

Rat SC LD50 (mg/kg)

119,400 in AD

55,230 in AD

390,300 in AD

193,400 in AD

2.

Rat IP LD50 Log10(mmol/kg)

Rat IV LD50 log10(mmol/kg)

Rat Oral LD50 log10(mmol/kg)

Rat SC LD50 log10(mmol/kg)

-0,311 in AD

-0,927 in AD

0,487 in AD

-0,047 in AD

Rat IP LD50 (mg/kg)

Rat IV LD50 (mg/kg)

Rat Oral LD50 (mg/kg)

Rat SC LD50 (mg/kg)

231,900 in AD

56,080 in AD

1457,000 in AD

425,500 in AD

 

Table 3

Acute classification of rodent toxicity by chemicals by OECD project using GUSAR software product 1

1.

Rat IP LD50 Classification

Rat IV LD50 Classification

RatOral LD50 Classification

Rat SC LD50 Classification

Class 4 in AD

Class 4 in AD

Class 4 in AD

Class 4 in AD

2.

Rat IP LD50 Classification

Rat IV LD50 Classification

RatOral LD50 Classification

Rat SC LD50 Classification

Class 4 in AD

Class 4 in AD

Class 4 in AD

Class 4 in AD

 

From table 3 it can be concluded that the toxicity of both compounds is low, 4 hazard classes.

Thus, the results obtained by predicting the biological activity using the PASS program, and the toxicity of the studied compounds using the GUSAR software product allow us to conclude that compound 1 is more active than 2, and the toxicity of both compounds is equal. Therefore, compound 1 has a higher potential activity, and this compound can be used prospectively for further laboratory studies.


Библиографическая ссылка

Diyarova N.R., Tovkaleva E.V., Ermolaeva A.A., Lavrova O.M. PREDICTION OF BIOLOGICAL ACTIVITY AND TOXICITY OF 5-DIETHOXYPHOSPHORYL4-ETHOXY-5-ETHOXYCARBONYL-2 – (1-IMINO)ETHYLTHIO-4,5-DIHYDROTHIAZOLE AND ITS DERIVATIVES // Материалы МСНК "Студенческий научный форум 2024". – 2020. – № 3. – С. 59-60;
URL: https://publish2020.scienceforum.ru/ru/article/view?id=152 (дата обращения: 29.03.2024).

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