Design and synthesis of novel chalcones as potent selective monoamine oxidase-B inhibitors

A novel series of substituted chalcones were designed and synthesized to be evaluated as selective human MAO-B inhibitors. A combination of either methylsulfonyl or trifluoromethyl substituents on the aromatic ketone moiety with a benzodioxol ring on the other end of the chalcone scaffold was investigated. The compounds were tested for their inhibitory activities on both human MAO-A and B. All compounds appeared to be selective MAO-B inhibitors with Ki values in the micromolar to submicromolar range. Molecular modeling studies have been performed to get insight into the binding mode of the synthesized compounds to human MAO-B active site. 2016 Elsevier Masson SAS. All rights reserved.This work was supported by internal grants (# QUST-CPH-FALL-14?15-9 and QUST-CPH-SPR-14/15-9 ) from the Office of Academic Research, Qatar University , Doha, Qatar. C.B. is member of the collaborative network within the COST Action CM1103, Structure-based drug design for diagnosis and treatment of neurological diseases . We are grateful to Professor Neal Castagnoli Jr. Professor Emeritus, Virginia Tech for providing the MMTP substrate. The 2D-NMR spectra were recorded by Professor Khalid Elsayed, University of Louisiana at Monroe, USA.Scopu