Pharmacological evaluation of newly synthesized benzimidazole derivative for anti-Alzheimer potential

Abstract

Backgound: Alzheimer disease (AD) is a disastrous disease characterized by accretion of amyloid-beta plaques, neurofibrillary tangles inducing oxidative stress, loss of neuronal functions and continuous progression of cognitive impairment leading to severe dementia.

Material and Methods: The newly synthesized benzimidazole derivative 4-chloro-3-(2-phenyl-1H-benzimidazole-1-sulfonyl) benzoic acid (CB) was evaluated for its anti-Alzheimer activity using in silico, in vivo, in vitro and molecular techniques (ELISA, WB & IHC).

Results: In-silico studies revealed that CB has atomic contact energy values of −3.9 to −8.9 kcal/mol against selected targets. In vitro assay showed that CB caused acetylcholinesterase (AChE) and diphenyl-1-picrylhydrazyl inhibition. In-vivo findings revealed improvement in dementia as observed in the morris water maze test and Ymaze test. Amyloid-beta disaggregation, increased level of anti-oxidants, decreased expressions of inflammatory markers and enhanced cellular architecture were found in the cortex and hippocampus of treated rats in the histopathological examination, immunohistochemistry analysis, enzyme-linked immunosorbent assay and western blot analysis.

Conclusions: This study revealed that CB possess different binding affinities with the Alzheimer-related targets and it possess anti-Alzheimer activity, mediated via AChE and amyloid-beta inhibition, anti-oxidant and anti-inflammatory pathways.

Keywords:

• 4-chloro-3-(2-phenyl-1H-benzimidazole-1-sulfonyl) benzoic acid
• molecular docking
• anti-Alzheimer amyloid-betaeta inhibition
• anti-oxidant
• anti-inflammatory

Acknowledgement

The authors are thankful to Riphah International University administration for providing research facility.

Authors’ contributions

AA, AU and HM conceived and designed research. MI and HM synthesized the compound. AA and NI conducted experiments. AA, AU, MI analyzed data. AA wrote the manuscript. NI reviewed the final draft. All authors read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.