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

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.

GRAPHICAL ABSTRACT

Keywords:

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

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

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