Identification of Indole-Based Chalcones: Discovery of a Potent, Selective, and Reversible Class of MAO-B Inhibitors

Sasidharan R., Manju S. L., UÇAR G., BAYSAL İ., Mathew B.

ARCHIV DER PHARMAZIE, vol.349, no.8, pp.627-637, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 349 Issue: 8
  • Publication Date: 2016
  • Doi Number: 10.1002/ardp.201600088
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.627-637
  • Hacettepe University Affiliated: Yes


A series of 11 indole-based chalcones (IC1-11) with various electron donating and withdrawing groups at the para position of the phenyl ring B were synthesized. All the compounds were tested for their human monoamine oxidase (hMAO)-A and hMAO-B inhibitory potencies. Most of the synthesized candidates proved to be potent and selective inhibitors of MAO-B rather than MAO-A, with a reversible and competitive mode. Among them, compound IC9 was found to be a potent inhibitor of hMAO-B with K-i = 0.01 +/- 0.005 mu M and a selectivity index of 120. It was found to be better than the standard drug, selegiline (hMAO-B with K-i = 0.20 +/- 0.020 mu M) with a selectivity index of 30.55. PAMPA assays were carried out for all the compounds in order to evaluate the capacity of the compounds to cross the blood-brain barrier. Moreover, the most potent MAO-B inhibitor, IC9, was nontoxic at 5 and 25 mu M, with 95.20 and 69.17% viable cells, respectively. The lead compound IC9 has an antioxidant property of 1.18 Trolox equivalents by ABTS assay. Molecular modeling studies were performed against hMAO-B to observe binding site interactions of the lead compound.