Acetyl-l-carnitine (ALC) is synthesized in the brain, liver, and kidneys and plays crucial roles in energy metabolism, acetylcholine production, protein synthesis, and neuronal protection, contributing to its antidepressant and neuroprotective properties. In this study, we present a novel multifunctional zinc complex, Zn(ALC)Cl2(H2O), which crystallizes in the monoclinic chiral space group P21, featuring a distorted tetrahedral Zn(II) environment. This new compound demonstrates significantly higher antidepressant activity, reducing immobility in the forced swimming test by 54 % compared to commercial ALC.
Additionally, it exhibits in vivo antinociceptive properties, increases latency time, and proves effective in a diabetic neuropathy model by preventing the glucose-induced decrease in intracellular GSH levels. In vitro studies indicate that the complex can cross the blood-brain barrier and offer neuroprotection against glutamate-induced excitotoxicity and oxygen-glucose deprivation, with a drug classification of 10 versus 5 for ALC. These findings highlight Zn(ALC)Cl2(H2O) as a promising candidate for treating depression and neurodegenerative diseases.
J. Inorg. Biochem. 2025 Feb 21.
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