榄香烯衍生物的合成及抗癌活性研究

【作者】 张兴忠；

【导师】 董金华； 徐莉英；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2005， 硕士

【摘要】 本文简述了榄香烯及其衍生物的研究进展，并在前期研究基础上，以β-榄香烯为先导化合物合成了四类16个β-榄香烯氨基酸衍生物，其中有6个为β-榄香烯氨基酸甲酯类衍生物，3个为β-榄香烯氨基酸类衍生物，6个为氨基酸-（β-榄香烯-13-基）酯类化合物，1个为氨基酸-（1-氯-2-氢-β-榄香烯-13-基）酯类化合物。所合成的化合物均为未见文献报道，经¹H-NMR、IR和MS等波谱分析确证结构。优化了合成路线中脱羧基保护基和脱氨基保护基反应的反应条件，并总结了目标化合物的图谱特征。用SRB法测定了16个目标化合物对体外培养的三种人癌细胞Hela、SGC-7901和HL-60的增殖抑制作用。结果显示其中14个化合物对三种细胞或其中某一种细胞表现出较β-榄香烯强的增殖抑制作用。N-（β-榄香烯-13-基）色氨酸（Z-7）对上述三种细胞的抑制作用最强，IC₅₀值分别为13.8μmol／L，8.2μmol／L和11.7gmol／L。N-（β-榄香烯-13-基）谷氨酸-1-甲酯（Z-6）和色氨酸-（β-榄香烯-13-基）酯（Z-10）具有一定的选择性抑制作用—前者对Hela细胞和HL-60细胞的IC₅₀值差别较大，分别为12.7gmol／L和81.8μmol／L：后者对HL-60细胞的作用较差，IC₅₀值50.0μmol／L，对SGC-7901和Hela细胞的抑制作用较强，IC₅₀值分别为17.4μmol／L和13.8μmol／L。初步研究结果显示本论文所合成的β-榄香烯衍生物有较好的抗癌活性，值得进一步的研究。更多还原

【Abstract】 The development of elemene andβ-elemene derivatives were introduced briefly. Based on the analysis of the structural characteristics ofβ-elemene, sixteen new derivatives containing amino acid moiety were synthesized fromβ-elemene. Among them, 6 compounds were N-(β-elemene-13-yl)amino acid methyl ester, 3 compounds were N-(β-elemene-13-yl)amino acid, 6 derivatives were amino acidβ-elemene-13-yl ester and 1 compound was Methioninel-chloro-2-H-yl-β-ele-mene-13-yl ester. The structures of the target compounds were confirmed by MS, ~1H-NMR and IR spectra.Effects of reaction condition on hydrolysis of N-(β-elemene-13 -yl)amino acid ester and the selective removal of the N-BOC protecting group were studied in detail.Theseβ-elemene derivatives were tested for their anti-tumor inhibitory activity in vitro against HL-60, SGC-7901 and Hela cells derived from human beings by SRB method. Fourteen compounds showed more potent antiproliferative activity thanβ-elemene. N-(β-elemene-13-yl)Tryptophan (Z-7) showed significant inhibition against the three tumor cells, while N-(β-elemene-13-yl)Glutamic acid 1-methyl ester (Z-6) andβ-elemene-13-yl Tryptophan ester (Z-10) showed notable selectivity.The results revealed thatβ-elemene derivatives containing amino acid moiety were potent anti-tumor agents and worthy of further study.更多还原