色胺酮衍生物设计、合成及抗肿瘤活性构效关系研究

发布时间：2018-05-05 08:22

本文选题：色胺酮 + 吲哚醌　；参考：《有机化学》2016年01期

【摘要】：首先合成吲哚醌衍生4a~4f,氧化水解得到邻氨基苯甲酸衍生物5a~5d.以这两者为原料设计合成A和/或D环取代的色胺酮衍生物1a~1q.然后,以色胺酮6位酮羰基分别与水合肼、盐酸羟胺反应生成C环席夫碱结构.最后,以哌嗪结构取代B环嘧啶酮合成茚(1,2-b)喹喔啉-11-酮.共设计合成20个化合物,其中新化合物13个.对所合成化合物的结构经红外光谱、核磁氢谱、元素分析确证.测定所合成化合物对肿瘤细胞A549的体外抑制活性.结果表明化合物1b,1c,1i,1j,1p和1q表现出较强的肿瘤细胞抑制活性,IC50值分别为3.58,0.99,1.03,2.10,0.51和0.43μmol·L-1.构效关系研究表明:D环卤素取代提高抗肿瘤活性,而取代基团在A环时则减弱抗肿瘤活性;B环(嘧啶环)被哌嗪环取代后抗肿瘤活性消失(IC50100μmol·L-1);而C环酮羰基生成席夫碱结构抗肿瘤活性与色胺酮相当.
[Abstract]:First, indoloquinone derived 4a~4f was synthesized by oxidative hydrolysis to obtain 5a~5d. of O aminophenyl formic acid derivative, which was designed to synthesize A and / or D ring substituted chroamone derivatives 1a~1q.. Then, the structure of C cyclic Schiff base was formed with hydrazine 6 acetone carbonyl with hydrazine and hydroxylamine hydrochloride respectively. Finally, the piperazine structure was substituted for B ring pyrimidone. The synthesis of 20 compounds, including 13 new compounds, was synthesized. The structure of the synthesized compounds was confirmed by IR, NMR, and elemental analysis. The inhibitory activity of the compound to the tumor cell A549 was determined. The results showed that the compound 1b, 1C, 1I, 1J, 1p and 1q showed strong tumor fines. Cytosolic activity, IC50 values of 3.58,0.99,1.03,2.10,0.51 and 0.43 Mu mol. L-1., respectively, showed that the substitution of D ring halogen to improve the antitumor activity, while the substituent group weakened the antitumor activity at the A ring, and the B ring (pyrimidine ring) was replaced by the piperazine ring after the anti tumor activity loss (IC50100 u mol L-1), while the C cycloone carbonyl formed Schiff base. The antitumor activity is equivalent to that of chroamone.

【作者单位】：西部资源生物与现代生物技术省部共建教育部重点实验室西北大学生命科学学院;西安市食品药品监督检验所;
【基金】：陕西省自然科学基金(No.2014JM4095) 陕西省教育厅基金(No.12JK1010) 陕西省重点科技创新团队计划(No.2013KCT-24)资助项目~~
【分类号】：O621.3

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