Design,Synthesis and Biological Evaluation of Novel(E)-Hydroxystyryl Aralkyl Sulfones as Neuroprotective Agents

摘要

A novel class of(E)-hydroxystyryl aralkyl sulfones were designed and synthesized as neuroprotective agents.Their neuroprotective properties were assessed by several antioxidant models including 1,1-diphenyl-2-picrylhydrazyl(DPPH)free radicals scavenging model,neuronal protective effects against neurotoxins such as hydrogen peroxide(H2O2),6-hydroxydopamine(6-OHDA)and 1-methyl-4-phenylpyridinium iodide(MPP+).Besides,the anti-inflammatory activity was evaluated by lipopolysaccharide(LPS)-induced nitric oxide(NO)release model in BV2 microglial cells.The result demonstrated that cinnamyl substituted compound 5h exhibited prominent antioxidant activity in H2O2 and 6-OHDA models and higher anti-inflammatory potency(IC_(50)=7.3 μM)than lead compound 1(IC_(50)=13.4 μM).Furthermore,compound 5h displayed predicted CNS(+)blood-brain barrier permeability(Pe=5.66×10~(-6)cms~(-1))in PAMPA model and low toxicity in PC12 and BV2 cells.These multifunctional properties highlight compound 5h is a promising candidate for further development against neurodegenerative diseases.