Multifunctional hybrid sulfonamides as novel therapeutic agents for Alzheimer’s disease
| Autor: | Ankit Ganeshpurkar, Dileep Kumar, Sushil Kumar Singh, Ravi Shankar Singh, Sukesh Kumar Gupta, Devendra Kumar, Sairam Krishnamurthy, Srabanti Jana, Rayala Swetha, Gopichand Gutti |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Modern medicine Amyloid β Cell Survival Disease Matrix Metalloproteinase Inhibitors Pharmacology 01 natural sciences Acetylcholine esterase 03 medical and health sciences Alzheimer Disease Chlorocebus aethiops Drug Discovery Animals Humans Medicine Computer Simulation Rats Wistar Maze Learning Vero Cells Butyrylcholinesterase Chelating Agents 030304 developmental biology Sulfonamides 0303 health sciences Amyloid beta-Peptides Molecular Structure 010405 organic chemistry business.industry Rats 0104 chemical sciences Molecular Docking Simulation Metal chelation Clinical trial Disease Models Animal Acetylcholinesterase Matrix Metalloproteinase 2 Molecular Medicine Cholinesterase Inhibitors business |
| Zdroj: | Future Medicinal Chemistry. 11:3161-3178 |
| ISSN: | 1756-8927 1756-8919 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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