Stability of Structure, Chemical Properties, and Biological Effects of Diacyl Derivatives of Dibenzo-18-crown-6

The interplay between Ca2+ ions and neuronal dysfunction has recently gained significant attention. A growing body of evidence implicates Ca2+ in the pathophysiology of neurodegenerative disorders, including Parkinson's disease. The rate of protein aggregate formation, mitophagy, and autophagy abnormalities in Parkinson's disease may be influenced by Ca2+ ions, and specific ionophores have been used to study this phenomenon. We investigated the potential of diacyl derivatives of dibenzo-18-crown-6 (DB18C6), namely 4′,4′′(5′′)-dibutyryl-DB18C6 and 4′,4′′(5′′)-divaleryl-DB18C6 and 4′,4′′-diacetyl-DB18C6 as an alternative to these specific ionophores. Our study provides evidence that both 4′,4′′(5′′)-dibutyryl-DB18C6 and 4′,4′′(5′′)-divaleryl-DB18C6 can effectively promote Ca2+ transport across fibroblast cell membranes at 10 and 100 nanomolar concentrations. Notably, the studied crown ethers do not appear to impact intracellular pH or mitochondrial membrane potential. Also, we assessed these molecules' structural stability and chemical purity, confirming their integrity and suitability for future research. These results suggest that using crown ethers as ionophores may be a promising alternative to specific ionophores in studying the impact of Ca2+ ions on various cellular processes in Parkinson's disease.