Antipyretic action of the new hydrazides 2 - (5 - (adamantane-1-yl)-4-r-1 ,2,4-triazol-3-ylthio)acetate

Abstract

INTRODUCTION. It is known that fever is a necessary defense response that activates the immune system, enhances phagocytosis, stimulates the formation of Interferon, antibody production, which leads to inhibition of reproduction of many viruses and bacteria. However, the raising of the temperature above 39 ° C is dangerous for adults and children of all ages.

Despite the high efficacy of analgesics, antipyretics, their use is not always safe. Therefore, the search for new highly efficient drug with antipyretic action is an urgent problem nowadays.

RESEARCH GOAL - was pharmacological antipyretics screening among first synthesized derivatives of 1,2,4-triazoles.

MATERIALS AND METHODS of research. The experimental fever reproduced on white nonlinear rats by administering 2,4-dinitrophenol (2,4-DNP) (disconnector of the oxidative phosphorylation) at a dose of 20 mg / kg.

Investigated substances were injected through 0.5 hours (T _0,5) after administration of 2,4-DNP, rectal body temperature for 1 hour (T₁) was fixed. Initial rectal temperature (T₀) recorded to intra-abdominal injection 2.4-DNF.

Acetylsalicylic acid was used as a comparison reference drug at a dose of 100 mg / kg.

The results were processed with modern statistical methods of analysis on a personal computer using standard software package Microsoft Office 2010 (Microsoft Excel) and «STATISTICA ® for Windows 6.0». We used 3 levels of statistical significance of differences in outcomes research - p <0.05, p <0.01, and P <0.001.

RESULTS AND DISCUSSION. A new antipyretics were identified with activity not less than in the standard for comparison - acetylsalicylic acid.

Intraabdominal injection of 2,4-DNF in 0.5 hour caused a fever in rat in average from 37.480 to 38.580 C^o (Δ 1,10 C). Most significantly retarded the body temperature in animals compound number 76 (ΔT 1,230 C, p <0.01), 86 (ΔT 1,140 C, p <0.001), 85 (ΔT 1,330 C, p <0.01), 87 (ΔT 1,010 S , p <0.01), it’s action were somewhat higher than antipyretic action of acetylsalicylic acid (ΔT 0,980 C, p <0.05).

CONCLUSIONS. The most active among the studied compounds was 5 - (adamantane-1-yl)-4-phenyl-4H-1,2,4-triazoles-3-yl-2-((5-nitrofurans-2-yl)aliliden)hydrazinekarbotiate . Its ability to inhibit the activity of hyperthermia was more than of acetylsalicylic acid in 35,7% (ΔT 1,330 C, p <0.01). Compounds 76, 86 and 87 exceed the activity of acetylsalicylic acid in 25,5% (ΔT 1,230 C, p <0,01), 16,32% (ΔT 1,140 C, p <0.001) and 3,06% (ΔT 1,010 C p <0.01), respectively. Introduction of phenyl methyl radical instead of N4 nitrogen atom in the molecule 5 - (adamantane-1-yl)-4-R-4H-1 ,2,4-triazoles-3-yl 2 - (3-nitrobenzyliden)-hidrazinekarbotiate associated with antipyretic effect.

Key words: 1,2,4-triazole derivatives, antihypoxic activity, hypoxia, antihypoxants.