Why p-OMe- and p-Cl-β-Methylphenethylamines display distinct activities upon MAO-B binding

Angélica Fierro, Dale E. Edmondson, Cristian Celis-Barros, Marco Rebolledo-Fuentes, Gerald Zapata-Torres

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Despite their structural and chemical commonalities, p-chloro-β-methylphenethylamine and p-methoxy-β-methylphenethylamine display distinct inhibitory and substrate activities upon MAO-B binding. Density Functional Theory (DFT) quantum chemical calculations reveal that β-methylation and para-substitution underpin the observed activities sustained by calculated transition state energy barriers, attained conformations and key differences in their interactions in the enzyme's substrate binding site. Although both compounds meet substrate requirements, it is clear that β-methylation along with the physicochemical features of the para-substituents on the aromatic ring determine the activity of these compounds upon binding to the MAO B-isoform. While data for a larger set of compounds might lend generality to our conclusions, our experimental and theoretical results strongly suggest that the contrasting activities displayed depend on the conformations adopted by these compounds when they bind to the enzyme.

Original languageEnglish
Article numbere0154989
JournalPLoS ONE
Issue number5
Publication statusPublished - 1 May 2016
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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