Structure-activity relationship of neuroprotective and reactive oxygen species scavenging activities for allium organosulfur compounds.
The neuroprotective and antioxidative activities of five organosulfur compounds with a thioallyl structure (-S-CH2CH=CH2) were characterized in terms of structure-activity relationships. Among five organosulfur compounds, only S-allyl-L-cysteine (SAC) having the alanyl group (-CH2CH-NH2-COOH) and lacking the oxo (O=) group with in between molecular properties, was effective in protecting cell death induced by both oxygen glucose deprivation and global cerebral ischemia. Conversely, lipophillic organosulfur compounds including diallyl sulfide, diallyl disulfide, and diallyl trisulfide were devoid of in vitro and in vivo neuroprotective activities. Furthermore, a significant correlation was only found between the in vivo neuroprotective activity and the OH- scavenging activity (gamma = 0.55 and p = 0.032) among reactive oxygen species scavenging activities. These results indicate that the presence of the alanyl group and the absence of the oxo group are essential for the manifestation of neuroprotective activity against ischemic insults and scavenging of OH radical, with SAC surfacing as a potent neuroprotectant.
Kim
Ji-Myung
JM
Korea Food Research Institute, San 46-1, Backhyun, Bundang-gu, Sungnam, Kyonggi-do 463-746, Korea.
Chang
Hyun Joo
HJ
Kim
Won-Ki
WK
Chang
Namsoo
N
Chun
Hyang Sook
HS
D000490:Allium / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002545:Brain Ischemia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D005849:Gerbillinae; D006801:Humans; D008297:Male; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000517:prevention & control; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000737:chemistry / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013457:Sulfur Compounds