Open AccessImplication of novel bis‐imidazopyridines for management of A lzheimer's disease and establishment of its role on protein phosphatase 2 A activity in brain
Author(s) -
Parekh Kauntay D.,
Dash Ranjeet Prasad,
Pandya Amit N.,
Vasu Kamala K.,
Nivsarkar Manish
Publication year - 2013
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12149
Subject(s) - dephosphorylation , antioxidant , lipid peroxidation , phosphatase , superoxide dismutase , protein phosphatase 2 , pharmacology , alzheimer's disease , chemistry , inflammation , biochemistry , medicine , disease , enzyme
Objectives The objective of this study was to synthesize and identify potential leads for the management of A lzheimer'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 2 A ( PP2A ) activity in brain which is responsible for tau dephosphorylation and alleviation of AD . Key findings The results of our study identified NIPERAMCD ‐ KTB 7 (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 ‐ KTB 7 suggesting its potential role in management of AD . Conclusions These preliminary findings indicate that NIPERAMCD ‐ KTB 7 holds potential to serve as a basic lead for further structural modification and development of other new chemical entities for combating AD .