Design,Synthesis And Biological Evaluation Neuroprotection Activtity Of Celastrol Derivatives

Celastrol,a natural quinone methide triterpenoid was isolated from root bark of the traditional Chinese herb “Thunder of God Vine”(Tripterygium wilfordii Hook F.),showed extensive pharmacological activities,such as antioxidant,anti-cancer and anti-inflammatory.Neuroprotective activity was the first activity to be studied,showed effective.However,the poor water solubility and the narrow therapeutic window were the major side effects preventing further clinical trial.In order to retain celastrol’s neuroprotective activity with reduced its toxicity was the problem in focus.Structure modification of celastrol by chemical methods may offer an alternative way.According to the literatures,the mainly toxicity group of celastrol was C-3 position.Hence,a series of Celastrol derivatives which modified the C-2 and C-3 positions were obtained using chemical methods and identified by the basis of spectroscopic methods.Celastrol and all the series of Celastrol derivatives were evaluated for their cytotoxicity and potential neuroprotective activity on pc12 cell lines were determined by MTT method,employing Edaravone as positive control drugs.The structure activity relationship were also discussed.The A and B rings of celastrol were the active site and the side chain on C-28 had little effect on the activities.It was found that forming an oxazole ring with the C-2 and C-3 of celastrol may reduce the toxicity.