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研究12种番荔枝内酯类化合物对耐阿霉素肝癌细胞SMMC-7721/ADR的作用,并初步探究其构效关系。实验利用实时荧光定量PCR法检测12种番荔枝内酯类化合物:annosquamin A(1),annosquamin B(2),annotemoyin~(-1)(3),uvariamicinⅡ(4),annosquacin D(5),annosquacin B(6),isodesacetyluvaricin(7),uvarigrandin A(8),squamostatin D(9),squamostatin E(10),squamostatin A(11),12,15-cis-squamostatin A(12)对SMMC-7721/ADR细胞中相关基因NDUFV2的表达量。该研究发现所有受试化合物均使SMMC-7721/ADR中NDUFV2表达量有所下调,邻双四氢呋喃环型番荔枝内酯活性最强,而间双四氢呋喃环型番荔枝内酯活性最弱。内酯环与邻近的四氢呋喃环间碳数越少,作用越强;对于邻双四氢呋喃型番荔枝内酯化合物,链上含有的羟基个数越多,化合物作用可能越强;对于间双四氢呋喃型番荔枝内酯化合物,链上含有的羟基个数越少,化合物作用可能越强;且受试化合物中均是含有3个羟基取代的化合物作用较强;相对构型为苏式的番荔枝内酯的作用比赤式的强,四氢呋喃环为顺式构型的番荔枝内酯的作用比反式的强;在其他基团完全相同的情况下,长链烷基端部与邻近的四氢呋喃环之间的碳数越少,作用越强。
To investigate the effects of 12 kinds of annona on the doxorubicin-resistant hepatocellular carcinoma SMMC-7721 / ADR, and to explore its structure-activity relationship. Twelve kinds of annona compounds were detected by real-time fluorescence quantitative PCR: annosquamin A (1), annosquamin B (2), annotemoyin -1 (3), uvariamicinⅡ (4), annosquacin D squamostatin D (9), squamostatin E (10), squamostatin A (11), 12,15-cis-squamostatin A (12) / ADR cells related gene NDUFV2 expression. This study found that all of the tested compounds caused a down-regulation of NDUFV2 expression in SMMC-7721 / ADR with the highest activity of o-biotin-cyclic annona lactone and the weakest activity of meta-di-tetrahydrofuran cyclo-luanone lactone. The more the carbon number between the lactone ring and the adjacent tetrahydrofuran ring is smaller, the stronger the effect is. For the o-dihydrofuran type annona lactone compound, the more hydroxyl groups contained in the chain, the stronger the effect of the compound may be. Lactone compounds, the lower the number of hydroxyl groups contained in the chain, the stronger the effect of the compound; the stronger the compound containing three hydroxyl substitutions in the tested compounds is; the relative configuration of the annotate The effect of the annotator annona is stronger than that of trans in the erythro-strong erythro-annone ring. Where the other groups are identical, the long-chain alkyl end and the adjacent tetrahydrofuran ring The smaller the carbon number, the stronger the effect.