Comparative Assessment of Cognitive Effects of Anthranilamide Derivatives

Anthranilamides have attracted increasing attention due to their antispasmodic and anti-inflammatory effects. Preclinical evidence suggests that these compounds may affect acetylcholinesterase activity, which could indirectly enhance cognitive performance. Therefore, the present study aimed to comparatively evaluate the effects of three previously synthesized anthranilamides, namely 2-chloro-N-(2-(phenethylcarbamoyl)phenyl)benzamide (1), 2-amino-N-(3-chlorophenethyl)benzamide (2), and 2-(2-chloro-2-phenylacetamido)-N-(3,4-dimethoxyphenethyl)benzamide (3), on cognitive functions in rats and to find them as potential active substances for neurodegenerative diseases treatment. In silico calculations, using SwissADME, Pro-Tox II, and PASS online, were performed. Two-way active avoidance test, activity cage test, and two passive avoidance tests – step-through and step-down test, were conducted. Overall, the obtained results imply that the anthranilamide scaffold has effects on cognitive processes, but these effects can be significantly altered by structural modifications. Our results demonstrate that anthranilamide derivatives do not produce a pronounced depressant or stimulant effect on the central nervous system. Two of the compounds, (1) and (2), showed cognitive-enhancing properties, with effects varying depending on the behavioral test applied, while compound (3)'s structural features might be less promising for this activity. These findings highlight the potential of specific anthranilamide derivatives as modulators of learning and memory processes. Therefore, the current results offer an initial SAR framework for more anthranilamide derivative improvement.