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.
Bibliographical noteFunding Information:
Funds for this study were supported by the Korea Institute of Science and Technology (KIST) ( 2E25240 , 2E25473 ) and by grants from the Korea Health Technology R&D Project , the Ministry of Health and Welfare ( HI12C1022 , KDP ).
© 2015 Elsevier Ltd.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry