Monoamine Oxidase Inhibitory Activity of Ferulic Acid Amides: Curcumin-Based Design and Synthesis


Badavath V. N. , BAYSAL İ. , UÇAR G. , Mondal S. K. , Sinha B. N. , Jayaprakash V.

ARCHIV DER PHARMAZIE, cilt.349, ss.9-19, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 349 Konu: 1
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1002/ardp.201500317
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Sayfa Sayıları: ss.9-19

Özet

Ferulic acid has structural similarity with curcumin which is being reported for its monoamine oxidase (MAO) inhibitory activity. Based on this similarity, we designed a series of ferulic acid amides 6a-m and tested for their inhibitory activity on human MAO (hMAO) isoforms. All the compounds were found to inhibit the hMAO isoforms either selectively or non-selectively. Nine compounds (6a, 6b, 6g-m) were found to inhibit hMAO-B selectively, whereas the other four (6c-f) were found to be non-selective. There is a gradual shift from hMAO-B selectivity (6a, b) to non-selectivity (6c-f) as there is an increase in chain length at the amino terminus. In case of compounds having an aromatic nucleus at the amino terminus, increasing the carbon number between N and the aromatic ring increases the potency as well as selectivity toward hMAO-B. Compounds 6f, 6j, and 6k were subjected to membrane permeability and metabolic stability studies by in vitro assay methods. They were found to have a better pharmacokinetic profile than curcumin, ferulic acid, and selegiline. In order to understand the structural features responsible for the potency and selectivity of 6k, we carried out a molecular docking simulation study.