LAUSR

A series of N-alkyl-1,4-dihydroquinoline prodrugs of scutellarin methyl ester have been synthesized (4a–4f). Compared to the parent compound scutellarin, we demonstrated that these prepared compounds had higher water solubility, more appropriate logP and better stability. Importantly, compounds 4a–4e showed improved neuroprotective activity against the H2O2-induced cell death in PC12 cells, and higher cell permeability (Papp AP–BL) and lower efflux ratio were observed for compounds 4d and 4e. The optimized compound 4d was further evaluated by cerebral ischemia/reperfusion in the middle cerebral artery occlusion (MCAO) model and could decrease the neuronal cell damage in CA1 pyramidal neurons in rats, inhibit the activation of autophagy protein beclin 1 and downregulate the expression of apoptotic protein caspase-3.