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

Synthesis and Biological Evaluation of Novel rasagiline analogues
as potential neuroprotective agents
C. Pereira¹, E. Borges¹, F. Aguiar¹, X. Garcia-Mera²
1 Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Portugal.
2 Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela,
Spain.
Neurodegenerative diseases are one of the major causes of death in aged population all over the
world. The Alzheimer’s disease (AD) is the most common amongst these, followed by the
Parkinson’s disease (PD). The existing therapies against AD and PD are still very far from
doctor and patient’s expectations. In this way, the drawing of new therapeutical
neuroprotective agents is a great challenge, in order to improve the effectiveness of the existing
drugs, or to introduce new alternative therapies.
Neuroprotection has two protagonists, selegiline and
rasagiline, propargylaminic drugs usually used in PD
treatment as monoamine oxidase-B (MAO-B) inhibitors.
Rasagiline has been mentioned in diverse studies as being
therapeutically superior in comparison with selegiline, this fact has
motivated a more detailed study of its action mechanisms and the
attainment of synthetic derivatives aiming to increase its neuroprotective effects.
In this work, we propose the synthesis of new rasagiline derivatives, which replaces the
rasagiline’s benzenic rinc by a pyridinic ring, and the evaluation of the neuroprotective
activity, which will allow us to establish potential activity against AD and PD.
The chemical synthesis will be done in due to provide a enough number of new compounds
endowed with molecular diversity in the pentacyclic ring from 6,7-dihydro-5Hcyclopenta[b]pyridine,
commercially available. Classic synthetic methodologies will be used,
in order to prepare different chemical precursors which will enhance the chemical diversity. In
a first step, racemic mixtures will be obtained and, later, the enatiomeric pure compounds will
be achieved through chemical or enzymatic resolution of the racemates or through
enantioselective synthetic processes.
The biological evaluation will be carried out by MAO, AchE and BchE inhibitory activity
measure, using selegiline and rasagiline as standards.
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[2]. D. R. Guay. Am. J. Geriatr. Pharmacother. 4(4). 330-46. 2006
[3]. W. Maruyama, M. B. Youdim, M. Naoi. Ann N Y Acad Sci. 939. pp. 320-329. 2001
[4]. W. Zhu, W. Xie, T. Pan, J. Jankovic, J. Li, M. B. Youdim e W. Le. J. Neurochem. 105. pp 1970–
1978. 2008
[5]. M. B. Youdim, et all. Ann N Y Acad Sci. 993. pp 378-86; 2003
326 3 rd meeting of young researchers at UP