&lt;strong&gt;Synthesis of fluorescent &lt;em&gt;O&lt;/em&gt;-Coumarin glycosides as Potential drug delivery systems for MAO inhibitors &lt;/strong&gt;

Antonio Franconetti,Francisca Cabrera-Escribano,José G Férnandez-Bolaños,Óscar López,Pastora Borrachero

doi:10.3390/ecsoc-19-a024

Abstract

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.

Highlights

Nowadays, the high prevalence and incidence1 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
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. In this communication we report the synthesis of coumarinyl glycosides by reaction of a glycosyl halide with coumarin derivatives and their characterization
An optimization of reaction conditions was performed in order to obtain the desired coumarinyl glycoside instead of elimination byproduct 11 which synthesis is mediated by unexpected dehydrohalogenation in the reaction medium

Summary

Introduction

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.. Both enzymes present different tissue distribution, physiological function and substrate specificity These isoforms act on a variety of endogenous and exogenous amine derivatives as neurotransmitters.. Coumarins have demonstrated to provide a wide range of biological activities including MAO inhibitor capability.6 This kind of compounds shows fluorescent properties that improving its detection at physiological environments. 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 In this communication we report the synthesis of coumarinyl glycosides by reaction of a glycosyl halide with coumarin derivatives and their characterization. The determination of the enzymatic parameters has shown that the carbohydrate-coumarin derivative is an efficient drug-releasing system

Experimental Methods

General Procedure for glycosylation reactions

Results and discussion

Conclusions