Acute toxicity of 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-1,2,4-triazole-3-thiol alkyl derivatives

D M Danilchenko,V V Parchenko

doi:10.14739/2310-1210.2016.5.82700

Abstract

The purpose of our work was the further exploration of the new 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-1,2,4-triazole-3-thiol alkyl derivatives’ acute toxicity, setting some patterns of alkyl substituents influence by the Sulfur atom on the acute toxicity. Research materials and methods. In this study we used first time synthesized 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-4 H -1,2,4-triazole-3-thione derivatives. Acute toxicity was conducted on white rats weighing 160–250 g, which were injected once intraperitoneally with the investigated substances. The rats were received from the nursery of the Pharmacology and Toxicology Institute of Ukraine Medical Sciences Academy. The animals were kept on a standard diet with natural light mode day-night. Results and their discussion. After the acute toxicity studies in a group of 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-4 H -1,2,4-triazole 3-alkyl derivatives it was found that among all studied structures the most toxic was 2e , LD 50 of which was 263 mg/kg, and the least toxic compound was 2a , LD 50 of which was 1570 mg/kg, that belongs to the V toxicity class. After comparing the acute toxicity of well-known antimycotic agent fluconazole with the studied compounds it can be argued that most compounds are less toxic than the comparison drug fluconazole with the index of LD 50 ˃320 mg/kg. It was found that the transition in a group from butyl to decyl, octyl, ventyl, propyl, nonyl and heptyl substituents in the molecule of 3-alkylthio 5-(furan-2-yl)-4-amino-4 H -1,2,4-triazole is accompanied by the toxicity increasing. Speaking about the 5-(2-metylfuran-3-yl)-4-amino-4 H -1,2,4-triazole 3-alkylthio derivatives we can find that this dependence is observed in a number from propyl, pentyl, nonil, butyl, heksyl, octyl and heptyl hydrocarbon chains. Conclusions. The investigated 3-alkylthio 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-4 H -1,2,4-triazole derivatives belong to the IV-V toxicity class. The toxicity of 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-4 H -1,2,4-triazole alkyl derivatives varies depending on the hydrocarbon substituents, so the presence of 3-heptylthiol substituent in the С 3 atom at 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-4 H -1,2,4-triazole leads to the toxicity increase. Introduction of 3-butylthiol to the molecule of 5-(furan-2-yl)-4-amino-4 H -1,2,4-triazole, and the 3-propylthiol substituents in the 5-(2-metylfuran-3-yl)-4-amino-4 H -1,2,4-triazole results the formation of lowest acute toxicity

Highlights

A significant contribution to the development of modern chemistry of heterocyclic compounds have scientific achievements of domestic scientists, who are engaged in the research of 1,2,4-triazole system for many years
After the acute toxicity studies in a group of 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-4H-1,2,4-triazole 3-alkyl derivatives it was found that among all studied structures the most toxic was 2e, LD50 of which was 263 mg/kg, and the least toxic compound was 2a, LD50 of which was 1570 mg/kg, that belongs to the V toxicity class
It was found that the transition in a group from butyl to decyl, octyl, ventyl, propyl, nonyl and heptyl substituents in the molecule of 3-alkylthio 5-(furan-2-yl)-4-amino-4H-1,2,4-triazole is accompanied by the toxicity increasing

Summary

Introduction

A significant contribution to the development of modern chemistry of heterocyclic compounds have scientific achievements of domestic scientists, who are engaged in the research of 1,2,4-triazole system for many years. Modeling the 1,2,4-triazole heterocycle by attaching different functional substituents results the formation of promising compounds, new “libraries” for further chemical reactions, the study of biological properties, different patterns installation. Scientific publications demonstrate the relevance and perspective of 1,2,4-triazole derivatives study which contain the remains of furan heterocyclic system and amino groups as typical substituents. The authors convincingly demonstrated that an active “symbiosis” of 1,2,4-triazole, furan and amino groups in one molecule has positive effect on the new compounds’ properties. Was noted [1] that further testing of new 5- (furan-2-yl, 2-metylfuran-3-yl)-4-amino-1,2,4-triazole3-thiol derivatives is important to have theoretical and practical significance. The purpose of our work was the further exploration of the new 5-(furan-2-yl, 2-metylfuran-3-yl)-4-amino-1,2,4-triazole3-thiol alkyl derivatives’ acute toxicity, setting some patterns of alkyl substituents influence by the Sulfur atom on acute toxicity

Objectives

Results

Conclusion