Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer's disease

被引:30
|
作者
Swetha, Rayala [1 ]
Kumar, Devendra [1 ]
Gupta, Sukesh K. [1 ]
Ganeshpurkar, Ankit [1 ]
Singh, Ravi [1 ]
Gutti, Gopichand [1 ]
Kumar, Dileep [1 ]
Jana, Srabanti [1 ]
Krishnamurthy, Sairam [1 ]
Singh, Sushil K. [1 ]
机构
[1] Banaras Hindu Univ, Dept Pharmaceut Engn & Technol, Indian Inst Technol, Varanasi 221005, Uttar Pradesh, India
关键词
beta-alanine; acetylcholine esterase; Alzheimer's disease; amyloid beta; butyrylcholinesterase; confocal fluorescence microscopy; matrix metalloproteinase-2; metal chelation; AMYLOID-BETA; MATRIX METALLOPROTEINASES; INHIBITORS; DERIVATIVES; OLIGOMERS; PEPTIDES; TAU;
D O I
10.4155/fmc-2019-0106
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 mu M) and BuChE (IC50: 1.32 +/- 0.02 mu M). It also exhibited a metal-chelating property, as validated by an in vitro metal-induced A beta 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.
引用
收藏
页码:3161 / 3177
页数:17
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