双吡啶α,β-不饱和酮抗肿瘤药物的细胞摄取研究

Cellar Uptake of Pyridine-substituted α,β-Unsaturated Ketones Antitumor Drugs

以4-吡啶甲醛与环己酮或N-甲基-4-哌啶酮通过Claisen-Schmidt缩合得到两个吡啶取代的α,β-不饱和酮药物,并通过1HNMR、FT-IR、元素分析等表征其结构。CCK-8法评价其对A549、MCF-7、He PG2、SGC-7901、OVCA-433等肿瘤细胞系的抗肿瘤活性及对正常细胞HUVEC的细胞毒性。研究显示,2,6-二(4-吡啶亚甲基)-1-环己酮对胃癌SGC7901和肝癌He PG2,药物3,5-二(4-吡啶亚甲基)-4-哌啶酮对A549、SGC7901、He PG2均有较好的抑制活性,其中IC50<10μmol/L,但对正常细胞HUVEC的细胞毒性较小。此外,通过共聚焦显微成像技术,实时检测了He PG2细胞对两种药物体外的摄取情况,随着药物浓度的升高和作用时间的不断延长,荧光强度也不断增强,说明细胞对药物的摄取量与时间和浓度呈正相关关系。

Two pyridine-substituted α,β-unsaturated ketone drugs were prepared by Claisen-Schmidt condensation reaction of 4-pyridinecarboxaldehyde with cyclohexanone or N-methyl-4-piperidinone. The compounds were confirmed by FT-IR,1HNMR and elemental analysis. The antitumor activities against human neoplastic cell lines A549,He PG2,MCF-7,SGC-7901,OVCA-433 and the cytotoxicities for HUVEC cell lines by CCK-8 method,which were subsequently evaluated. Some IC50 values were lower than10 μmol / L,while the cytotoxicities were markedly lower. In addition,cellular uptake of（ 2,6-bis（（ pyridin-4-yl） methylene） cyclohexanone）（ A） and（ N-methyl-3,5-bis（（ pyridin-4-yl） methylene） piperidin-4-one）（ B） by He PG2 cells was carried out by confocal fluorescence images. The result showed that fluorescent enhancement following the change of time and concentration,further demonstrated the increase of cellular uptake amount of A and B by He PG2 cells,which shows a positive correlation between cellular uptake amount and drug time and concentration.