The neuroprotective and antioxidative activities of five organosulfur compounds with a thioallyl structure(-S-CH
2CH=CH
2) were characterized in terms of structure-activity relationships. Among fiveorganosulfur compounds, only S-allyl-
L-cysteine (SAC) having the alanyl group (-CH
2CH-NH
2-COOH) and lacking the oxo (O=) group with in between molecular properties, was effective inprotecting cell death induced by both oxygen glucose deprivation and global cerebral ischemia.Conversely, lipophillic organosulfur compounds including diallyl sulfide, diallyl disulfide, and diallyltrisulfide were devoid of in vitro and in vivo neuroprotective activities. Furthermore, a significantcorrelation was only found between the in vivo neuroprotective activity and the OH
- scavenging activity(
= 0.55 and
p = 0.032) among reactive oxygen species scavenging activities. These results indicatethat the presence of the alanyl group and the absence of the oxo group are essential for themanifestation of neuroprotective activity against ischemic insults and scavenging of OH radical, withSAC surfacing as a potent neuroprotectant.