Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors

Ji Won Choi, Bo Ko Jang, Nam Chul Cho, Jong Hyun Park, Seul Ki Yeon, Eun Ji Ju, Yong Sup Lee, Gyoonhee Han, Ae Nim Pae, Dong Jin Kim, Ki Duk Park

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Abstract

We have synthesized three categories of α,β-unsaturated carbonyl derivatives and evaluated their MAO-A and MAO-B inhibitory activities. Among them, compound 10b including α,β-unsaturated ketone group showed the most potent and selective MAO-B inhibitory activity (IC50 human MAO-B 16 nM, >6000-fold selective vs MAO-A) and compound 10b exhibited good reversibility compared with selegiline, a well-known irreversible MAO-B inhibitor. However, both α,β-unsaturated amide and ester derivatives exhibited weaker MAO-B inhibition potencies. The docking studies provided insights into the possible binding modes and the key interaction sites of the synthesized MAO-B inhibitors.

Original languageEnglish
Article number12516
Pages (from-to)6486-6496
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number19
DOIs
Publication statusPublished - 2015 Oct 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Choi, J. W., Jang, B. K., Cho, N. C., Park, J. H., Yeon, S. K., Ju, E. J., Lee, Y. S., Han, G., Pae, A. N., Kim, D. J., & Park, K. D. (2015). Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors. Bioorganic and Medicinal Chemistry, 23(19), 6486-6496. [12516]. https://doi.org/10.1016/j.bmc.2015.08.012