3rd meeting of young researchers at UP 1 - IJUP - Universidade do ...

Development of potent and selective MAO-B inhibitors: structureactivity
relationship studies on chromone scaffold
J. Reis 1 , G. Pamplona Pinto 1 , A.Fonseca 1 , N. Milhazes 1,2 , A. Gaspar 1 , F. Borges 1
1 CIQ(UP)/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto,
Portugal.
2 ISCSN, P-4585116 Gandra, PRD Portugal
Parkinson disease (PD), is a neuroprogressive and incurable disorder with no real treatment,
although some drugs are available to control the symptoms and/or slow down the progress of
the disease. Levodopa (L-DOPA), a dopamine precursor, is the mainstay of the current therapy
but it has tolerance problems and a wide range of adverse reactions, like involuntary
movements and vomiting. The inadequacy of the current pharmacotherapy and the lack of
drugs that can be effective in PD are the reasons why the discovery of novel chemical entities
(NCE) is still a demand.
Monoamine oxidase (MAO) inhibitors, specifically of MAO-B type, are considered useful
tools for the treatment of PD. When used in combination with levodopa, inhibitors of MAO-B
may enhance the elevation of dopamine levels after levodopa treatment, particularly when used
in early stages of the disease when dopamine production may not be so severely compromised.
Furthermore, MAO-B inhibitors may also possess neuroprotective properties in part by
reducing the damaging effect of dopamine turnover in the brain. The MAO-B inhibitor effects
are especially relevant when considering that the brain shows an age-related increase in MAO-
B activity.
Based on these observations one can take advantage in the management of PD throughout the
design of novel MAO-B drugs since a selective inhibitor have not been found yet. In fact the
rational design of new chemical entities is a niche in the large field of drug discovery and
opens the possibility of the discovery of innovative drugs that may have enhanced therapeutic
potential in the treatment of PD.
The main goal of the project is the rational discovery of new chemical entities (NCE), based on
benzopyrane structure possessing potent and selective MAO-B activity as a novel and
promising treatment approach for Parkinson disease.
The rational design and structure-activity-relationships data obtained so far will be presented in
this communication.
References:
Borges, F et al. “Novel chromone derivatives, methods of synthesis therefor and use as
antioxidants/preservatives” (PCT/IB2008/050674)
Borges, F et al. “Cromonas e derivados de cromonas com actividade inibidora da monoamina oxidase e
aplicações terapêuticas relacionadas” (PT10448)
382 3 rd meeting of young researchers at UP