title: Neuroprotective and Antioxidant Activities of 4-Methylcoumarins: Development of Structure-Activity Relationships.
abstract: 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.
authors: Bioorganic Laboratory, Department of Chemistry, University of Delhi.
authors: Shashwat
authors: S
authors: Malhotra
authors: Marjan
authors: M
authors: Tavakkoli
authors: Najmeh
authors: N
authors: Edraki
authors: Ramin
authors: R
authors: Miri
authors: Sunil Kumar
authors: SK
authors: Sharma
authors: Ashok Kumar
authors: AK
authors: Prasad
authors: Luciano
authors: L
authors: Saso
authors: Christophe
authors: C
authors: Len
authors: Virinder Singh
authors: VS
authors: Parmar
authors: Omidreza
authors: O
authors: Firuzi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D005290:Ferric Compounds / Q000737:chemistry; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010851:Picrates / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D002712:Chlorides; D003374:Coumarins; D005290:Ferric Compounds; D018696:Neuroprotective Agents; D010851:Picrates; D017382:Reactive Oxygen Species; C004931:1,1-diphenyl-2-picrylhydrazyl; C024555:ferric chloride