Toxicity and antioxidant activity of 4-hydrazinoquinoline derivatives

Abstract

Annotation. 4-hydrazinoquinoline derivatives have a wide pharmacological potential. The study of their biological properties showed that they have not only antimalarial, antituberculosis, antiviral activity, but also are good antioxidants. First of all, the toxicity of investigated compounds has been evaluated in silico and in vivo. Software solutions were used for building “structure-toxicity” models and predicting LD50 with the help of GUSAR (Germany), TEST (USA) models. Experimental studies were carried out on 64 white mice without a breed of both sexes weighing 16-24 g. Derivatives of 4-hydrazinoquinoline are classified as low and moderately toxic compounds. Antioxidant activity was investigated on 10 4-substituted quinoline compounds and compared with reference drugs. For the research we used the native material – ejaculates of fertile men (normozoospermia). For this purpose, the indicators of the standard spermogram were previously evaluated according to generally accepted methods in accordance with WHO criteria. Oxidative stress (OS) was created in cells with the help of 3% hydrogen peroxide. To protect against OS caused by hydrogen peroxide, the studied compounds and comparative drugs with AO properties (AK and ACC) were used. The obtained results were processed using the program “STATISTICA® for Windows 6.0” (StatSoft Inc, No. АХХР712D833214FAN5) by methods of variational statistics using the Student’s t-test. Investigating the average speed of motile spermatozoa, it was found that compounds with residues of acetic and pentanedioic acids exceeded the comparison drugs. (Е)-2-(2-(7-chloroquinolin-4-yl)hydrazono)acetic acid demonstrated a stronger effect on 8-10 % than the comparative drug ACC. Disodium (Е)-2-(2-(2-methylquinolin-4-yl)hydrazono)pentanedioate has an advantage over the level of action of AA by 15%. Derivatives of (2-(quinolin-4-yl))hydrazono)carboxylic acids in the conditions of H2O2-induced OS were generally inferior to comparison drugs AA and ACC. These results demonstrate that derivatives of (2-(quinolin-4-yl))hydrazono)carboxylic acids exhibit favorable antioxidant properties and are promising protectors of spermatozoa in OS conditions. The studied series of quinoline derivatives requires both further in-depth studies of the mechanisms of AO protection and favorable structural modifications in this series.