Neuroprotective and Antioxidant Activities of 4-Methylcoumarins: Development of Structure-Activity Relationships
| Autor: | Marjan Tavakkoli, Shashwat Malhotra, Ramin Miri, Virinder S. Parmar, Omidreza Firuzi, Sunil K. Sharma, Christophe Len, Ashok K. Prasad, Luciano Saso, Najmeh Edraki |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Antioxidant DPPH Cell Survival medicine.medical_treatment Pharmaceutical Science Oxidative phosphorylation Neuroprotection Ferric Compounds PC12 Cells Antioxidants 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Chlorides Picrates Dichlorofluorescein Coumarins medicine Animals Cytotoxicity Hydrogen peroxide Pharmacology Biphenyl Compounds 4-methylcoumarin neuroprotective PC12 cell neurodegenerative disease General Medicine Rats Oxidative Stress 030104 developmental biology Neuroprotective Agents chemistry Biochemistry Polyphenol Reactive Oxygen Species |
| Zdroj: | Biologicalpharmaceutical bulletin. 39(9) |
| ISSN: | 1347-5215 |
| Popis: | Coumarins are a major class of polyphenols that are abundantly present in many dietary plants and possess different biological activities. Neuroprotective effect of 28 variously substituted 4-methylcoumarins was evaluated in a cell model of oxidative stress-induced neurodegeneration, which measures viability in PC12 cells challenged with hydrogen peroxide by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of these compounds against intracellular reactive oxygen species (ROS) formation was also determined by 2',7'-dichlorofluorescein diacetate method in the same cells. Chemical redox-based assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) tests were employed to explore structure-antioxidant activity relationships in a cell-free environment. The results demonstrated that 4-methylcoumarins containing ortho-dihydroxy or ortho-diacetoxy substituents on the benzenoid ring possess considerable neuroprotective effects. ortho-Dihydroxy compounds inhibited cytotoxicity (44.7-62.9%) and ROS formation (41.6-71.1%) at 50 µM and showed considerable antioxidant effects. We conclude that 4-methylcoumarins are promising neuroprotective and antioxidant scaffolds potentially usefull for management of neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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