| 摘要: |
| 目的 在苯并吡喃酮和其3位取代苯基、酯基和羟甲基之间插入双键或三键结构，或将异黄酮类化合物的3’-或4’-氨基与去甲斑蝥素形成酰胺结构，以发现抗肿瘤活性更强的异黄酮类化合物。 方法 以丹皮酚和甲酸乙酯为原料，经多步反应制得关键中间体3-碘-7-甲氧基苯并吡喃酮(5)，再经Heck coupling反应和Sonogashira coupling反应分别制得3位有双键和三键取代基的目标化合物;经Suzuki coupling反应制得3’-或4’-氨基化合物，并与去甲斑蝥素反应制得酰胺目标化合物;通过1HNMR、MS和IR方法确定目标化合物的结构。选择人结肠癌细胞株HCT116和人肝癌细胞株SMMC 7721为实验瘤株，以姜黄素和大豆异黄酮为阳性对照测定体外抗肿瘤活性。 结果 设计合成的17个目标化合物均有一定的体外抗肿瘤活性，其中化合物7b和7e的活性较好，与对照品姜黄素的IC50值相当, 明显优于对照品大豆异黄酮的IC50值。 结论 在苯并吡喃酮和其3位取代苯基、酯基和羟甲基之间插入双键或三键不会降低目标化合物的抗肿瘤活性，可能会提高其抗肿瘤活性;但将异黄酮类化合物的3’-或4’-氨基与去甲斑蝥素形成酰胺似乎对提高其抗肿瘤活性没有多大帮助。 |
| 关键词: 苯并吡喃酮 Heck coupling反应 Sonogashira coupling反应 Suzuki Coupling反应 抗肿瘤药 |
| DOI：10.3724/SP.J.1008.2010.0864 |
| 投稿时间：2009-12-17修订日期：2010-06-02 |
| 基金项目: |
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| Synthesis of novel 3-(substituted phenyl) chromone derivatives and their anti-tumor activities |
| DONG Huan-wen1, ZHANG Yue-li2, LIU Jue-ying2, QUAN Zhen-hua1, LI Tie-jun3, LI Ke4,,LIU Chao-mei |
| (1. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;2. Department of Internal Medicine, Huadong Hospital of Fudan University, Shanghai 200040, China;3. Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;4. Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| Objective To search for new isoflavones with more potent antitumor activities from the target compounds synthesized by inserting a double bond or an acetylene bond between chromone and its 3-substituted phenyl, ester and hydroxymethyl groups, or by formation of an amide of 3’ or 4’-amino group of isoflavones with norcantharidin. Methods The key intermediate 3-iodo-7-methoxyl-4H-chromen-4-one (5) was prepared with 2-hydroxyl-4-methoxyl-acetophenone and ethyl formate. The target compounds with 3-substituted double bond or acetylene groups were synthesized by Heck coupling and Sonogashira coupling reaction; the amide compounds were synthesized by Suzuki coupling reaction and amide formation of 3’ or 4’-amino group of isoflavones with norcantharidin. All of the target compounds were confirmed by 1HNMR, MS and IR spectra. The IC50 values of target compounds were determined by the standard method using two kinds of human tumor cell lines, colon cancer cell line HCT116 and liver cancer cell line SMMC 7721 to study their anti-tumor activities. Results All the 17 target compounds obtained had certain anti-tumor effect in vitro, with compounds 7b and 7e showing better anti-tumor effects, which were similar to that of control curcumin and more potent than that of genistein in vitro. Conclusion The insertion of a double bond or an acetylene bond between chromone and its 3-substituted phenyl, ester and hydroxymethyl groups may promote the anti-tumor activities of isoflavone analogues. It seems that the formation of an amide of 3’- or 4’-amino group of isoflavones with norcantharidin has no noticeable promotion effect on the anti-tumor activities. |
| Key words: chromone Heck coupling reaction Sonogashira coupling reaction Suzuki coupling reaction antineoplastic agents |
