Apiol from Parsley Seeds as a Source for the Synthesis of Coenzyme Q₀ Propanoic Acid Conjugates with Amines Featuring...

Quinone-containing compounds are known for their free-radical scavenging activity and pronounced antioxidant properties. They could be promising for the alleviation of progressive neuronal damage in neurodegenerative diseases, caused in particular by oxidative stress. In this study, coenzyme Q₀ derivatives featuring the fragment of natural quinone propanoic acid conjugated with dopamine, 5-methoxytryptamine, β-alanine, and γ-aminobutyric acid were synthesized. Apiol, the main metabolite of parsley seed extract, was used as a starting material. The aim of this study was to explore antioxidant activity of the targeted compounds in vitro using several assays, including determination of free radical scavenging capacity, inhibition of lipid peroxidation in mouse brain homogenate, and evaluation of toxicity and membrane-protective effects in mouse red blood cells (RBCs). All conjugates of the quinone propanoic acid fragment demonstrated significant antioxidant activity. The free radical scavenging capacity of the compounds in DPPH and ABTS tests was associated with the presence and amount of unsubstituted OH groups in the aromatic ring. The dopamine derivative was identified as the most potent inhibitor of both oxidative mouse RBC hemolysis and intracellular generation of reactive oxygen species. The 5-methoxytryptamine quinone derivative considerably suppressed Fe^2+/ascorbate-initiated lipid peroxidation in the mouse brain homogenate. All compounds showed no toxicity on a sea urchin embryo model and could be considered potential neuroprotective agents due to the antioxidant properties of the quinone fragment and facile cleavage of the labile amide bond, thereby providing the targeted delivery of biogenic amines into the desired location.