Bi Wei, Cai Jianhui, Liu Sanguang, Baudy-Floc'h Michèle, Bi Lanrong
Second Hospital of HeBei Medical University, Shijiazhuang 050000, PR China.
Bioorg Med Chem. 2007 Nov 15;15(22):6909-19. doi: 10.1016/j.bmc.2007.08.022. Epub 2007 Aug 21.
In this study, a new class of phenolic tetrahydro-beta-carboline RGD peptidomimetic conjugates was designed and synthesized. The radical scavenging activities of these newly synthesized compounds 12a-c were evaluated in PC12 cell survival assays. The NO scavenging activities of these compounds were confirmed in the acetylcholine-induced vasorelaxation assay. Compounds 12a-c were efficacious in a rat arterial thrombosis model, and were active in ADP- or PAF-induced in vitro platelet aggregation assays, which suggests these compounds also possess anti-thrombotic activity. The beneficial effects of dual-acting agent 12c were demonstrated on the ischemia-reperfusion induced cardiac infarct size and oxidative change in an in vivo rat model.
在本研究中，设计并合成了一类新型的酚类四氢-β-咔啉RGD拟肽缀合物。在PC12细胞存活试验中评估了这些新合成化合物12a - c的自由基清除活性。在乙酰胆碱诱导的血管舒张试验中证实了这些化合物的一氧化氮清除活性。化合物12a - c在大鼠动脉血栓形成模型中有效，并且在ADP或PAF诱导的体外血小板聚集试验中具有活性，这表明这些化合物也具有抗血栓活性。在体内大鼠模型中证明了双效剂12c对缺血再灌注诱导的心脏梗死面积和氧化变化具有有益作用。
