Acute toxicity and "structure-action" dependence of 4-(R-benzylidenamino)-5-methyl-4H-1,2,4-triazoles 3-tion

Abstract

The achievements of modern pharmaceutical chemistry allow to develop a wide range of potential new drugs. However, their success in clinical practice depends on their safety. Therefore, the presence of evidence of their safety and efficacy is an integral part of any research. The aim of our study was to investigate acute toxicity of synthesized 1,2,4-triazoles derivatives, studying behavioral reactions to toxic doses and dependence "structure – action". Methods. To install middle lethal dose (LD50) the substance was administered intraperitoneally as an aqueous suspension stabilized by Tween-80. The substance was administrated once to four groups of laboratory animals (white nonlinear rats), 2 animals in each group. Multiple doses were administered, including the dose which does not cause the death of any animal and the dose which causes the death of all animals in the group. After administration of the compounds we conducted surveillance for two weeks to all animals who stayed alive. Results. The least toxic compound among the studied 4-(R-benzylidenamino)-5-methyl-4H-1,2,4-triazoles-3-thiones was compound 1 with an index of 840 mg/kg, which contains 4-methoxybenzilidene substituent on N4-nitrogen atom and the most toxic was compound 5, which has 4-brombenzilidene substituent at the same prosition (LD50 – 284 mg/kg). So we see that replacing bromine atom leads to the reduction of toxic properties. So we can assume that the introduction of a halogen atom to benzilidene phenolic core substituent increases the toxic properties of the synthesized compounds. An interesting pattern is observed for compounds 2–4, which contain two methoxy substituents, and their LD50 almost did not changed and range from 764 to 790 mg/kg. Conclusions. The study has found that 4-(R-benzylidenamino)-5-methyl-4H-1,2,4-triazol-3-tiones belonging to IV Class of toxicity. In addition, these compounds can be subjected to further biological study.

Keywords

• toxicity tests
• preclinical drug evaluation
• 4-triazole
• biological activity