Discovery of novel 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives as multifunctional MAO-B inhibitors for the treatment of Parkinson's disease

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2159957. doi: 10.1080/14756366.2022.2159957.

Abstract

To discover novel multifunctional agents for the treatment of Parkinson's disease, a series of 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives was designed, synthesized and evaluated. The results revealed that representative compound 3h possessed potent and selective MAO-B inhibitory activity (IC50 = 0.062 µM), and its inhibitory mode was competitive and reversible. Additionally, 3h also displayed excellent anti-oxidative effect (ORAC = 2.27 Trolox equivalent), significant metal chelating ability and appropriate BBB permeability. Moreover, 3h exhibited good neuroprotective effect and anti-neuroinflammtory ability. These results indicated that compound 3h was a promising candidate for further development against PD.

Keywords: 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives; MAO-B inhibitors; Parkinson’s disease; anti-neuroinflammatory agents; multifunctional anti-PD agents.

MeSH terms

  • Benzothiazoles / pharmacology
  • Humans
  • Hydroxyl Radical
  • Molecular Structure
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Neuroprotective Agents* / pharmacology
  • Parkinson Disease* / drug therapy
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase
  • Benzothiazoles
  • Neuroprotective Agents
  • Hydroxyl Radical

Grants and funding

This work was supported by Nanchong Science and Technology Program (22SXQT0021) and Doctoral startup Fund of North Sichuan Medical College (CBY21-QD15).