Abstract
Alzheimer disease (AD) is the leading cause of dementia and accounts for 60–80% cases. Two main factors called β-amyloid (Aβ) plaques and tangles are prime suspects in damaging and killing nerve cells. However, oxidative stress, the process which produces free radicals in cells, is believed to promote its progression to the extent that it may responsible for the cognitive and functional decline observed in AD. As of today there are few FDA-approved drugs in the market for treatment, but their cholinergic adverse effect, potentially distressing toxicity and limited targets in AD pathology, limits their use. Therefore, it is crucial to find an effective compounds to combat AD. We choose 45 plant-derived natural compounds that have antioxidant properties to slow down disease progression by quenching free redicals or promoting endogenous antioxidant capacity. However, we performed molecular docking studies to investigate the binding interactions between natural compounds and 13 various anti-Alzheimer drug targets. Three known cholinesterase inhibitors (donepezil, galantamine and rivastigmine) were taken as reference drugs over natural compounds for comparison and drug-likeness studies. Few of these compounds showed good inhibitory activity besides antioxidant activity. Most of these compounds followed pharmacokinetic properties that make them potentially promising drug candidates for the treatment of Alzheimer disease.
Pharmacokinetic and molecular docking studies of 45 natural antioxidant compounds with most known Alzheimer-associated targets
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Acknowledgements
The authors are grateful to the Centre for Interdisciplinary Research in Basic Sciences (CIRBSc), Jamia Millia Islamia for providing the research infrastructure.
Aftab Alam is supported by a research fellowship of the University Grants Commission, Government of India; SA and MZM are supported by the Indian Council of Medical Research under SRF (Senior Research Fellowship).
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The authors report no conflicts of interest in this work.
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Alam, A. et al. (2018). Pharmacokinetic and Molecular Docking Studies of Plant-Derived Natural Compounds to Exploring Potential Anti-Alzheimer Activity. In: Choudhary, D., Kumar, M., Prasad, R., Kumar, V. (eds) In Silico Approach for Sustainable Agriculture. Springer, Singapore. https://doi.org/10.1007/978-981-13-0347-0_13
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