Antihypoxic activity of benzylidenhydrazides of 4-R-5- (thiophene-2-ylmethyl)-1,2,4-triazol-3-il)thioacetic acid

Abstract

In recent years we see significant increase of natural and technogenic situations that lead to disorders of functional and metabolic processes of central nervous system and cardiovascular diseases, including acute cerebrovascular accident. The leading factor in vascular brain pathology is hypoxia. Currently all body states, in which we see any reason decrease of oxygen delivery to tissues is considered as hypoxia. Paying into account the fact that available pharmacotherapeutic agents for the oxygen deficiency treatment tend to have limited efficacy, narrow range of active doses and often cause undesirable side effects, the special attention is paid to drugs that have an antihypoxic action and exclude the above mentioned effects.Aim. To study antihypoxic actions for the first time synthesized derivatives of 1,2,4-triazoles and to find the "structure - action" dependence.Materials and methods. Antihypoxic activity of 1,2,4-triazoles derivatives was studied at modeling hypoxia with hypercapnia. Rats were placed in same volume (1330 ml) sealed up jars, then overturned them down and put in a cell with water to prevent the flow of air. As a comparison drug in the study we used mexidol 100 mg / kg.Results. The study has identified three compounds that extend the comparison drug mexidol and prolong the life expectancy of 59.94 %, 47.79% and 53.31% (compounds 1, 2, 5, respectively). While mexidol was 42.54%. After analyzing the data and chemical structure of the synthesized compounds we have established some relative patterns between chemical structure and antihypoxic actions of 1,2,4-triazoles derivatives.Conclusions. As the result of the study, we have discovered the compound that exceeds the referent drug mexidol on 17.4%. In the study of the acute toxicity of 1,2,4-triazoles derivatives it was found that all compounds belong to IV Class of toxicity (LD50 = 331-770 mg / kg). The presence of two halogen atoms in the molecules of benzylidenhydrazides of 4-R-5-(thiophene-2-ylmethyl)-1,2,4-triazol-3-il) thioacetic acid shows expressive antihypoxic action.