Benzo[ b]tiophen-3-ol derivatives as effective inhibitors of human monoamine oxidase: design, synthesis, and biological activity

J Enzyme Inhib Med Chem. 2019 Dec;34(1):1511-1525. doi: 10.1080/14756366.2019.1653864.

Abstract

A series of benzo[b]thiophen-3-ols were synthesised and investigated as potential human monoamine oxidase (hMAO) inhibitors in vitro as well as ex vivo in rat cortex synaptosomes by means of evaluation of 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio and lactate dehydrogenase (LDH) activity. Most of these compounds possessed high selectivity for the MAO-B isoform and a discrete antioxidant and chelating potential. Molecular docking studies of all the compounds underscored potential binding site interactions suitable for MAO inhibition activity, and suggested structural requirements to further improve the activity of this scaffold by chemical modification of the aryl substituents. Starting from this heterocyclic nucleus, novel lead compounds for the treatment of neurodegenerative disease could be developed.

Keywords: MAO-B inhibitors; Parkinson’s disease; antioxidant activity; benzothiophene; molecular modelling; rat cortex synaptosomes.

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase

Grants and funding

This work was supported by “Progetto di Ricerca Ateneo La Sapienza 2014-C26A14AC5L” (Italy) and POR FESR LAZIO 2014/2020 – REGIONE LAZIO – Avviso pubblico LIFE 2020 (Prof. Daniela Secci). The monoamine oxidase inhibition experiments were supported by grants from the National Research Foundation of South Africa (Grant specific unique reference numbers (UID) 85642, 96180). Opinions expressed and conclusions arrived at, are those of the authors and therefore the NRF do not accept any liability in regard thereto.