Synthesis of fluorescent O-Coumarin glycosides as Potential drug delivery systems for MAO inhibitors

Nowadays, the high prevalence and incidence of neurodegenerative diseases, such as Parkinson, Alzheimer or amyotrophic lateral sclerosis diseases makes an important field to search for novel molecules to access different customized treatment. In this context, monoaminooxidase (MAO) inhibitors have been used for this purpose in the initial stage of Parkinson’s disease.

Coumarins have demonstrated to provide a wide range of biological activities including MAO inhibitor capability. Additionally, this kind of compounds shows fluorescence properties improving its detection at physiological environments. However, these compounds often suffer from poor solubility. With the aim of solving this drawback, following the strategy carrier pro-drug, coumarin attachment to a carbohydrate residue allowed us to improve this disadvantage.

Herein, we report the synthesis and characterization of coumarin glycosides by reaction of a glycosyl halide with coumarin derivatives. The reaction has been optimised to achieve good selectivities and yields. For this purpose, mechanistic considerations based on DFT calculations have been also performed. Finally, the determination of the enzymatic parameters has shown that the carbohydrate-coumarin derivative is an efficient drug-releasing system.We thank the AECID (Projects A/023577/09 and A/040322/10) and the ‘Junta de Andalucía’ (FQM 142 and Project P09-AGR-4597) for financial support.