[The design and synthesis of 2-aminothiazole derivatives and their inhibitory activity on apoptosis].
OBJECTIVE
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-alpha, 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 H2O2 were found in this experiment. The optimal QSAR equation obtained from the Cerius2-QSAR+ module by using log (1/EC50) with corresponding descriptors is Activity = 6.947 68 - 0.088 72 x "LUMO" - 0.043 018 x "Alogp98" - 0.128 752 x "Rad0fGration" + 0.018 246 x "Dipole-mag". The correlation statistics parameters of the above equation are as follows: r2 = 0.970, F-test = 49. 149, r = 0. 985 and Lse = 0. 001.


CONCLUSIONS
The 2-aminothiazole derivatives exhibited certain activity in inhibiting PC12 cell apoptosis induced by H2O2. Some compounds such as I-6, I-9 and II-6 have the dual activities, the protective action against and inhibitory action on PC12 cell apoptosis induced by H2O2. 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.
Jiang
Feng-chao
FC
School of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. fengchao@mails.tjmu.edu.cn
Cheng
Chong-yun
CY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016716:PC12 Cells; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D018696:Neuroprotective Agents; D013844:Thiazoles; C004483:2-aminothiazole; D006861:Hydrogen Peroxide