Actoprotective activity of 2-(4-r-3-(thiophen-2-yl)-4h-1,2,4-triazol-3-ylthio) acetic acid

Abstract

INTRODUCTION. The high temp of life, characteristic to a modern human, firmly leads to depletion of physical and mental strength. To improve the physical and mental activity of humans to normal and extreme conditions, a drugs of different origin are being used (synthetic, vitamins, herbal and animal origin, and also their tablet forms, infusion). But they have a number of side effects and also most of them are not registered in Ukraine. To solve this problem, a new class of low toxicity stimulants – actoprotectors can be used. In these group, a great interest is given to low-toxic derivatives of 1,2,4-triazoles, which have diuretic, antiviral, hypolipidemic, antipsychotic and other activities. THE AIM OF THE WORK was to study actoprotective activity of 2-(4-R-3-(thiophen-2-yl)-4H-1 ,2,4-triazol-3-iltio) acetic acid derivatives and to establish the structure-action dependence. MATERIALS AND METHODS OF THE EXPERIMENT. Experiments were conducted on a group of white, non-linear rats, weighing 200-260 g. At studying the actoprotective activity, a metod of compulsory immersion into water with the load of 10% of the weight of rat was used. The load was fixed to the rat’s tail. Swimming was performed till exhaustion, which was noted 10-seconds after immersion of laboratory animals in water. Rats were immersed in a container individually. Which contained a layer of 60 cm of water, at a temperature of 24-270С. The compounds which are under the study along with etalon of comparison - riboxin were administered in to the peritoneum of animal, 20 minutes before the immersion, at a dose of 100 mg / kg. The compounds were administered in a dose of 1/10 LD50. The swimming time was recorded in seconds. For comparison, a control group of animals, which have been given physiologic solution into the peritoneum, 20 minutes before the immersion, were used. RESULTS AND DISCUSSION. At the study of actoprotective activity of compounds, the compounds 2-(4-R-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-iltio) acetic acid shows an actoprotective activity in the range of 10,99% - 169,04%, when compared to control group. The most pronounced actoprotective activity was shown by sodium 2-(4-methyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-iltio) acetate, which contains a sodium cation and N4 nitrogen atom of 1,2,4-triazole cycle methyl substituent. At screening of the actoprotective activity of sodium 2-(4-phenyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-iltio)acetate , introduction potassium cations or a morpholyne did not show any significant results, but replacement of morpholyne cation by piperidine cation, made the activity to be increased almost in four times, when compared with the control group. CONCLUSIONS 1. All the studied compounds - derivatives of 2-(4-R-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-iltio)acetic acid, have show an actoprotective activity, except the piperidine 2-(5-(thiophene-2-yl)-4H-1,2,4-triazoles-3-iltio) acetate. 2. The most pronounced actoprotective activity was shown by sodium 2-(4-methyl-5-(thiophen-2-yl)-4H-1,2,4-triazoles-3-iltio)acetate and piperydyne 2-(4-phenyl-5-(thiophene-2-yl)-4H-1,2,4-triazoles-3-iltio)acetate. 3. The compound sodium 2-(4-methyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-iltio)acetate can be used for further deep studies.

Keywords

• actoprotective activity
• triazol
• cation