| 引用本文: | 侯阿芳,曾林伟,甘礼社,周文方,侯廷军,王燕兰,莫建霞,周长新.丹参新酮C环酚酯衍生物的设计合成及抗肿瘤活性研究[J].中国现代应用药学,2016,33(11):1396-1402. |
| HOU Afang,ZENG Linwei,GAN Lishe,ZHOU Wenfang,HOU Tingjun,WANG Yanlan,MO Jianxia,ZHOU Changxin.Design, Synthesis and Anti-tumor Activity Evaluation of New Miltirone Esters Derived From Ring C[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(11):1396-1402. |
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| 摘要: |
| 目的 通过对丹参新酮C环邻醌位点的结构修饰，改变其脂水分配系数，获得系列丹参新酮酚酯衍生物，进而评价其抗肿瘤活性。方法 采用氢化还原、酰化、脱保护基等方法对丹参新酮的邻醌位点进行修饰，通过引入不同酸酐、氨基酸取代基，得到丹参新酮C环酚酯衍生物，在此基础上以前列腺癌Lncap和Du145细胞株对部分化合物进行抗肿瘤活性评价。结果 共合成了9个新的丹参新酮酚酯衍生物，其中1个化合物表现出较好的抗肿瘤活性。结论 脂水分配系数对丹参新酮衍生物抗肿瘤活性影响很大，适当提高水溶性，有助于增强其抗肿瘤活性，改善成药性。 |
| 关键词: 丹参新酮衍生物 脂水分配系数 抗肿瘤活性 |
| DOI：10.13748/j.cnki.issn1007-7693.2016.11.010 |
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| Design, Synthesis and Anti-tumor Activity Evaluation of New Miltirone Esters Derived From Ring C |
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HOU Afang, ZENG Linwei, GAN Lishe, ZHOU Wenfang, HOU Tingjun, WANG Yanlan, MO Jianxia, ZHOU Changxin
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College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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| Abstract: |
| OBJECTIVE To synthesize miltirone ester derivatives with various lipid/water partition coefficients based on modification of quinone group, and evaluate the anti-tumor activities. METHODS Hydrogenation reduction, anhydride acylation and deprotection of Boc-groups were used to modify abietane o-quinone sites through introducing different anhydride, amino acid substituents and different miltirone C cyclic phenol ester derivatives were synthesized, on the basis of this, the anti-tumor activity of parts of compounds were evaluated by prostate cancer Lncap and Du145 cell lines. RESULTS Totally 9 miltirone derivatives were synthesized, among which 1 compound exhibited enhanced in vitro anti-tumor activities against Lncap and Du145 cell lines compared with miltirone. CONCLUSION The lipid/water partition coefficient has great influence on the anti-tumor activity of miltirone derivatives, structure modification to improve the hydrophilicity of miltirone can effectively enhance it's antitumor activity. |
| Key words: miltirone derivatives CLogP anti-tumor activity |
