synthesis of lipoamino acids and their activity against cerebral ischemic injury合成lipoamino酸和他们的活动对脑缺血性损伤.pdf

Molecules 2009, 14, 4051-4064; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis of Lipoamino Acids and Their Activity against Cerebral Ischemic Injury Li-Yun Yao, Qi Lin, Yin-Yao Niu, Ke-Min Deng, Jian-Hua Zhang and Yang Lu * Institute of Pharmaceutical Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China * Author to whom correspondence should be addressed; E-Mail: huaxue@. Received: 14 August 2009; in revised form: 22 September 2009 / Accepted: 29 September 2009 / Published: 12 October 2009 Abstract: A series of lipoamino acids were synthesized and their neuroprotective effect against brain ischemia induced by oxygen-glucose deprivation (OGD) on rat cerebral slices was evaluated. Among these compounds, N-stearoyl-L-tyrosine (4), N-stearoyl-L-serine (5) and N-stearoyl-L-threonine (6) exhibited good neuroprotective activity. We found that the neuroprotective activity of lipoamino acids depended on the acyl group, the presence of a free carboxylic function and a free hydroxyl group at the branched chain of the amino acids. The results also showed that 5 was the most active compound, protecting rat brain slices against OGD as well as hydrogen peroxide (H O ) insult at the range of 1–10 M. 2 2 Keywords: lipoamino acids; neuroprotection; brain ischemia; oxygen-glucose deprivation 1. Introduction Cerebral ischemia would lead