Acute toxicity and hypoglycemic activity of 7-chloro-4-thiosubstituted quinoline

Abstract

The search for effective and safe pharmacological drugs for the treatment of diabetes is remaining highly valuable issue due to the chronic course of the disease and the need to use antipyretic drugs during the rest of life. Currently, various hypoglycemic agents are presented in the pharmaceutical market and the safety of their application is in priority. The activity of 4-thio-7-chloroquinoline derivatives as potential hypoglycemic drugs was studied here. The hypoglycemic activity was determined using a One Touch Ultra Plus Flex meter. The approach to glucose determination by this method is based on the reaction of glucose contained in the blood sample with flavin adenine dinucleotide dependent glucose dehydrogenase in the test strip, with the formation of a small electric current. The strength of this current calculates the level of glucose in the blood serum. Sodium 3-(7-chloroquinolin-4-ylthio)propionate demonstrates a high hypoglycemic activity after its intragastric administration. This compound significantly reduces glucose levels in rats up to 18.1% when compared with baseline and other compounds. 2-(7-Chloroquinoline-4-ylthio)propane and 2-acetamido-3-(7-chloroquinolin-4-ylthio)propanoic acid had little or no effect on serum glucose. The administration of compound 3 3-(7-chloroquinolin-4-ylthio)propionic acid in experimental animals increases the serum glucose on 19,6% comparing to the basic level. Acute toxicity of 4-thio7-chloro-substituted quinoline was determined with the Prozorovsky express method. The substances were administered once intraperitoneally as a thin aqueous suspension in saline solution (stabilizer - Twin 80) or as a solution of not more than 1 ml. The relationship between the structure of the test compounds and their toxicity is analyzed. It has been established that the mean lethal dose (LD50) of these compounds ranges from 200-800 mg/kg and is classified as low toxic that corresponds to the fourth class of toxicity.