Novel arylalkenylpropargylamines as neuroprotective, potent, and selective monoamine oxidase B inhibitors for the treatment of Parkinson's disease

  • J Med Chem. 2015 Feb 12;58(3):1400-19. doi: 10.1021/jm501722s.
Paul B Huleatt  1 ,  Mui Ling Khoo ,  Yi Yuan Chua ,  Tiong Wei Tan ,  Rou Shen Liew ,  Balázs Balogh ,  Ruth Deme ,  Flóra Gölöncsér ,  Kalman Magyar ,  David P Sheela ,  Han Kiat Ho ,  Beáta Sperlágh ,  Péter Mátyus ,  Christina L L Chai
Affiliations
  • 1. Institute of Chemical and Engineering Sciences , A* STAR (Agency of Science, Technology and Research), 8 Biomedical Grove, Neuros #07-01, Singapore 138665, Singapore.
PMID: 25627172 DOI: 10.1021/jm501722s
Abstract

To develop novel neuroprotective agents, a library of novel arylalkenylpropargylamines was synthesized and tested for inhibitory activities against monoamine oxidases. From this, a number of highly potent and selective Monoamine Oxidase B inhibitors were identified. Selected compounds were also tested for neuroprotection in in vitro studies with PC-12 cells treated with 6-OHDA and rotenone, respectively. It was observed that some of the compounds tested yielded a marked increase in survival in PC-12 cells treated with the neurotoxins. This indicates that these propargylamines are able to confer protection against the effects of the toxins and may also be considered as novel disease-modifying anti-Parkinsonian agents, which are much needed for the therapy of Parkinson's disease.