Synthesis Of Tetrahydrocarbazole Derivatives And Primary Study Of Neuroprotective Effects

Alzheimer's disease(AD)is a form of neurodegenerative disease.The number of AD patients is gradually increasing with the accelerated aging problem.Now it is recognized that oxidative stress is a causal of Alzheimer's disease.The tetrahydrocarbazole derivatives are widely used in pharmaceutical chemistry with multiple kinds of biological activities.It was confirmed that the tetrahydrocarbazole derivatives possess good free radical scavenging ability.So it is valuable to do the research for the potent neuroprotective effects of the compounds.We obtained the tetrahydrocarbazole derivatives(Bi)catalyzed by VBI in mild reaction conditions.The way to synthesize tetrahydrocarbazole derivatives is environmentally friendly,and it expanded the use of VB1 in organic synthesis.This protocol relies on the use of substituted cyclohexanone and phenylhydrazine hydrochloride with electron-donating or electron-withdrawing groups to form tetrahydrocarbazole scaffolds with a wide scope.Most of the target products catalyzed by VB1 were obtained in good to excellent yields(>90%).This way has the advantages of substrate suitability and functional group tolerance.The innovation of this paper is the use of VB1.It acted as an efficient and non-toxic catalyst in the reaction,and VB1 could be reused without reducing the catalytic efficiency.Owing to the diversity biological activities of tetrahydrocarbazole,the way to synthesize tetrahydrocarbazole derivatives catalyzed by VB1 exists potential applications in the field of green pharmaceutical science.Then the N-substituted tetrahydrocarbazole derivatives(Ci)and carbazole derivatives(Ai)were obtained based on the way to synthesize Bi.The neuroprotective effects of the compounds(Ai,Bi,Ci)were evaluated in SH-SY5Y cells against H2O2-induced cytotoxity.It was found that the compounds B8,B10,B16,B21,B27,C1,A2 and A4 exhibit neuroprotective activity.Part of the compounds were selected for the test of inhibitory activity against NO production.It was carried out in RAW264.7 cells induced by LPS.The results showed that B10 and B16 possess good inhibitory effect.