Synthesis and biological evaluation of novel neuroprotective agents for paraquat-induced apoptosis in human neuronal SH-SY5Y cells.
Three types of resveratrol analogues were designed, synthesized and evaluated in vitro against paraquat-induced apoptosis in SH-SY5Y cells. The results showed that some compounds, especially those containing an indene core, exhibit good activities. Analogue 3'a showed a potent neuroprotective effect at a low concentration (10 μM). Further investigation showed that compound 3'a could attenuate paraquat-induced nuclear morphological changes, significantly decrease paraquat-induced ROS (reactive oxygen species) generation in SH-SY5Y cells and elevate the expression of SOD (Superoxide Dismutase) and GPx (glutathione peroxidase) in a dose-dependent manner. Furthermore, analogue 3'a could decrease Bax protein levels in a concentration-dependent manner and increase Bcl-2 protein expression, which was accompanied by increasing chances of cell survival.
Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Chen
C
Zhong
Xin-Hua
XH
Liu
Xiao-Dong
XD
Hao
Jun
J
Chang
Xun
X
Sun
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010269:Paraquat / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D010269:Paraquat