摘要/Abstract
为寻找高效的抗肿瘤活性化合物，设计并合成了一系列新型的去氢枞酸硝酸酯类化合物.采用噻唑蓝（MTT）法测定目标化合物对鼻咽癌（CNE-2）、肝癌（HepG2，BEL-7402）和宫颈癌（HeLa）细胞株以及人正常肝细胞株（HL-7702）和鼻咽上皮细胞株（NP69）的细胞毒活性.结果表明，大多数杂合物的细胞毒性明显高于母体化合物.其中，12-溴去氢枞酸-3'-硝氧基丙酯（5j）对鼻咽癌CNE-2细胞株的抑制增殖活性优于顺铂，IC50值为（8.36±0.14）μmol/L，12，14-二硝基去氢枞酸-3'-硝氧基丙酯（5n）对肝癌BEL-7402细胞株的IC50值为（11.23±0.21）μmol/L.同时，目标化合物对人正常肝细胞株（HL-7702）和鼻咽上皮细胞株（NP69）表现出较低的细胞毒性.此外，对所有硝酸酯的NO释放量的测试表明，在大多数情况下，细胞毒性与CNE-2细胞株细胞内NO的释放水平呈正相关.
关键词: 去氢枞酸, 硝酸酯, 合成, 细胞毒性
In order to find more effective antitumor agents, a series of novel dehydroabietic acid derivatives bearing nitrate moiety were designed and synthesized. Their cytotoxicities were evaluated against human cancer cell lines of CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical) and BEL-7402 (liver), and human normal liver cell (HL-7702) and nasopharyngeal epithelial cell (NP69) using methyl thiazolyl tetrazolium (MTT) assay. Biological screening results demonstrated that most of the hybrids exhibited more potent cytotoxicity superior to parent compound dehydroabietic acid. Among them, 12-bromodehydroabietic acid-3'-nitrooxypropyl ester (5j) displayed better antiproliferative activity with IC50value of (8.36±0.14) μmol/L toward CNE-2 cells compared with cisplatin, and 2,14-dinitrodehydroabietic acid-3'-nitrooxypropyl ester (5n) showed remarkable cytotoxicity with IC50 value of (11.23±0.21) μmol/L against BEL-7402 cells. Moreover, they exhibited lower cytotoxicity against human normal liver cell line HL-7702 and nasopharyngeal epithelial cell NP69. Besides, NO released amounts detection of all nitrates suggested that in most cases, the cytotoxicities were positively correlated with the levels of intracellular NO release in CNE-2 cells.
Key words: dehydroabietic acid, nitrate, synthesis, cytotoxicity
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