Implication of novel bis-imidazopyridines for management of Alzheimer's disease and establishment of its role on protein phosphatase 2A activity in brain

Abstract

Objectives: The objective of this study was to synthesize and identify potential leads for the management of Alzheimer's disease (AD).

Methods: A series of bis-imidazopyridines were synthesized and assessed preclinically for anti-inflammatory and antioxidant activity in aluminium chloride-induced rat model for AD. The two targets, anti-inflammatory and antioxidant, hold a significant relevance in AD. The compounds were also screened for their role of protein phosphatase 2A (PP2A) activity in brain which is responsible for tau dephosphorylation and alleviation of AD.

Key findings: The results of our study identified NIPERAMCD-KTB7 (dose: 50 mg/kg bodyweight, orally), as a potential molecule with good inhibitory activity in acute (67% oedema protection) as well as chronic (61% oedema protection) model of inflammation. This compound also showed good antioxidant activity as inferred from the inhibition of lipid peroxidation and superoxide dismutase activity in rats at the dose mentioned above. More significantly, PP2A activity was found to be increased in the brains of the animals treated with NIPERAMCD-KTB7 suggesting its potential role in management of AD.

Conclusions: These preliminary findings indicate that NIPERAMCD-KTB7 holds potential to serve as a basic lead for further structural modification and development of other new chemical entities for combating AD.

Keywords: Alzheimer's disease; PP2A activity; antioxidant; bis-imidazopyridines; inflammation.