ABSTRACT
Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method．The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.
ABSTRACT
6-Bromo-3-n-butylphthalide was obtained by nitration, reduction and diazotization from carboxybenzaldehyde. Twenty hybrids from substituted styrene and 6-bromo-3-n-butylphthalide were synthesized and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The mechanism of neuroprotection was investigated by Western blot analyses. The results indicated that most of these compounds had a potent neuroprotective activity (All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine), especially 10h and 10i showed significant effects, which may play a neuroprotective role by activating the PI3K/Akt signaling pathway.