摘要
目的研究2氨-基噻唑衍生物对神经细胞凋亡的抑制作用和构效关系。方法以PFTα-为先导物,设计并合成出相应的2-氨基噻唑衍生物,利用MTT法和FCM法测定其对由过氧化氢诱导产生的PC12细胞凋亡的抑制作用,利用Cerius2的QSAR+模块,求出其QSAR方程。结果合成了11个新型含2氨-基噻唑母环的Sch iff碱化合物II,利用IR,MS,1H NMR,13C NMR等法对上述化合物进行表征。细胞实验结果表明,2氨-基噻唑衍生物对PC12细胞具有一定的保护作用并对由过氧化氢诱导的PC12细胞凋亡具有一定的抑制作用。优化QSAR方程为Activity=6.947 68-0.088 72דLUMO”-0.043 018דA logp98”-0.128 752דRad0 fG ration”+0.018 246דD ipole-m ag”,上述方程的相关统计参数如下,r2=0.970,F-test=49.149,r=0.985,Lse=0.001。结论2氨-基噻唑衍生物对由过氧化氢诱导的PC12细胞凋亡具有较为明显的抑制作用,部分化合物如I-6,I-9和II-6对于PC12细胞具有细胞保护和细胞凋亡抑制双重活性。QSAR方程提示降低化合物的旋转半径以及化合物最低空轨道的能量有利于提高化合物的活性。
Aim To investigate the inhibitory effect of 2-aminothiazole derivatives on Neuro-cell apoptosis and QSAR. Methods The 2-aminothiazole derivatives were designed and synthesized based on the lead compound of PFT-α, the protective action of the compounds Ⅰ and Ⅱ against and their inhibitory action on PC12 cell apoptosis induced by H2O2 were determined by MTT method and FCM method. The QSAR equation was obtained from Cerius2-QSAR^＋ module. Results Eleven novel 2-aminothiazole Schiff base compounds （Ⅱ） have been designed and synthesized. The structure of the compound II were characterized by IR, MS,^1H NMR,^13C NMR. Their protective action against and the inhibitory action on PC12 cell apoptosis induced by H202 were found in this experiment. The optimal QSAR equation obtained from the Cerius2-QSAR^＋ module by using log （1/ECs0） with corresponding descriptors is Activity = 6. 947 68 -0. 088 72×＂LUMO＂ - 0. 043 018 ×＂Alogp98＂ - 0. 128 752× ＂Rad0fGration＂ ＋ 0. 018 246×＂Dipole-mag＂. The correlation statistics parameters of the above equation are as follows： r^2=0. 970, F-test = 49. 149, r = 0. 985 and Lse = 0. 001. Conclusion The 2-aminothiazole derivatives exhibited certain activity in inhibiting PC12 cell apoptosis induced by H202. Some compounds such as Ⅰ-6, Ⅰ-9 and Ⅲ-6 have the dual activities, the protective action against and inhibitory action on PC12 cell apoptosis induced by H202. The QSAR equation indicated that it is favorable for enhance the activity of 2- aminothiazole derivatives by the reduction of ＂ radius of gyration＂ and the energy of ＂ LUMO＂ of the compounds.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第8期727-734,共8页
Acta Pharmaceutica Sinica
