Multifunctional Hybrid Sulfonamides as Novel Therapeutic Agents for Alzheimer’s Disease

Abstract

Aim: A breakthrough in modern medicine, in terms of treatment of Alzheimer’s disease, is yet to be seen, as the scene is currently plagued with numerous clinical trial failures. Here, we are exploring multifunctional hybrid sulfonamides for their anti-Alzheimer activity due to the complex nature of the disease. Results & methodology: Compound 41 showed significant inhibition of MMP-2 (IC₅₀: 18.24 ± 1.62 nM), AChE (IC₅₀: 4.28 ± 0.15 μM) and BuChE (IC₅₀: 1.32 ± 0.02 μM). It also exhibited a metal-chelating property, as validated by an in vitro metal-induced Aβ aggregation assay using confocal fluorescence imaging. Whereas, MTT and DPPH assays revealed it to be nontoxic and neuroprotective with substantial antioxidant property. Conclusion: The present study puts forth potent yet nontoxic lead molecules, which foray into the field of multitargeted agents for the treatment of Alzheimer’s disease.

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Graphical abstract

Keywords: :

• β-alanine
• acetylcholine esterase
• Alzheimer’s disease
• amyloid β
• butyrylcholinesterase
• confocal fluorescence microscopy
• matrix metalloproteinase-2
• metal chelation

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Acknowledgments

The authors would like to thank G M Martin at the University of Washington, Seattle for providing the MC65 cells.

Financial & competing interests disclosure

Authors acknowledge the research support from Department of Biotechnology (DBT), New Delhi, India (File No. BT/PR9624/MED/30/1253/2013 dated-29/11/2014). R Swetha, SK Gupta, A Ganeshpurkar, R Singh, G Gutti and S Jana would like to thank the Ministry of Human Resource Development, New Delhi for the award of Teaching Assistantship to them. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.