Design, synthesis, and biological activities of novel Ligustrazine derivatives.
A series of novel Ligustrazine derivatives was designed, synthesized, and assayed for their protective effects on damaged ECV-304 cells and antiplatelet aggregation activities. The results showed that most Ligustrazine derivatives exhibited lower EC(50) values for protective effects on the ECV-304 cells damaged by hydrogen peroxide in comparison with Ligustrazine. And some Ligustrazine derivatives presented better antiplatelet aggregation activities than Ligustrazine. The derivatives containing the bisphenylmethyl pharmacophore (7a-c) exhibited highest potency. Compound 7a displayed most potential protective effects on the ECV-304 cells damaged by hydrogen peroxide, and compound 7c was found to be the most active antiplatelet aggregation agent. Structure-activity relationships were briefly discussed.
Cheng
Xian-Chao
XC
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.
Liu
Xin-Yong
XY
Xu
Wen-Fang
WF
Guo
Xiu-Li
XL
Ou
Yang
Y
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002460:Cell Line; D002855:Chromatography, Thin Layer; D015195:Drug Design; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000633:toxicity; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared
D007202:Indicators and Reagents; D016877:Oxidants; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D006861:Hydrogen Peroxide; C017953:tetramethylpyrazine