Effects of a Tacrine Analogue on Behavioral and Biochemical Parameters in Drosophila melanogaster

The development of tacrine derivatives aims to evaluate their biological potential as inhibitors of acetylcholinesterase and butyrylcholinesterase, enzymes involved in the cholinergic system. In this study, we aimed to synthesize 1,3,4,10-tetrahydroacridin-9(2H)-one (THA), a tacrine analogue, and examined the effects of a THA-supplemented diet on behavioral and biochemical parameters in Drosophila melanogaster. Drosophila melanogaster was fed a diet supplemented with THA at different concentrations from the larval stage until the fifteenth day of adulthood. A diet containing 0.025 mM THA increased mortality after 10 days of feeding. However, larvae fed 0.1875 mM THA showed no toxic effects. Biochemical analyses revealed that ingesting 0.1875 and 0.250 mM THA elevated nitrite, hydrogen peroxide, and lactate levels in the flies' thoraces. Notably, 0.1875 and 0.250 mM THA increased citrate synthase activity in the thorax and head of the flies. However, 0.1875 mM THA showed higher acetylcholinesterase activity only in the thorax, suggesting cholinergic modulation in muscle. These findings suggest that THA supplementation supports neural and muscle health in this animal model and may be a potential treatment for chronic diseases.