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采用衍生法,在N-[4-叔丁基-5-(4-氯苄基)噻唑-2-基]脂肪酰胺酰基的α-位,插入氨基,设计合成了N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺衍生物.以4,4-二甲基-1-芳基-3-戊酮为原料,经4-叔丁基-5-苄基-2-氨基噻唑(3),再经氯乙酰化和取代反应得21个N-(4-叔丁基-5-苄基噻唑-2-基)氨基乙酰胺(1),其结构经~1H NMR、~(13)C NMR和元素分析确证.噻唑蓝(MTT)法体外抗肿瘤活性测试表明,该类新化合物对肺癌细胞(A549)、宫颈癌细胞(Hela)和乳腺癌细胞(MCF-7)具有抗肿瘤活性.其中N-[4-叔丁基-5-(胡椒基)噻唑-2-基]吗啉基乙酰胺(1t)对Hela细胞的抑制活性最好;对优选化合物1t进行了AO/EB双染和细胞周期实验,流式细胞仪分析表明,化合物1t可显著诱导肿瘤细胞凋亡,阻滞Hela细胞有丝分裂在S期.
Amino groups were inserted at the α-position of N- [4-tert-butyl-5- (4-chlorobenzyl) thiazol- Benzylthiazol-2-yl) aminoacetamide derivatives Starting from 4,4-dimethyl-1-aryl-3-pentanone and 4-tert-butyl-5-benzyl -2-aminothiazole (3), and then 21 N- (4-tert-butyl-5-benzylthiazol-2-yl) aminoacetamide (1) was obtained by the reaction of chloroacetylation and substitution. The results of 1H NMR, 13 C NMR and elemental analysis confirmed that the anti-tumor activity of MTT assay showed that the new compounds could inhibit the growth of lung cancer cells (A549), cervical cancer cells (Hela) and breast cancer cells -7) had antitumor activity, among which the inhibitory activity of N- [4-tert-butyl-5- (piperonyl) thiazol-2-yl] morpholinoacetamide (1t) on Hela cells was the best; 1t were used for AO / EB double staining and cell cycle assay. Flow cytometry analysis showed that compound 1t could significantly induce tumor cell apoptosis and block Hela cell mitosis in S phase.