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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SMMC7721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。
OBJECTIVE To insert a double or triple bond between benzopyrone and its 3-substituted phenyl group, ester group and hydroxymethyl group or combine the 3’- or 4’-amino group of isoflavones with norcantharidin The amide forms an amide structure to find more isoflavone-resistant compounds. Methods The key intermediates 3-iodo-7-methoxybenzopyranone (5) were obtained via multiple steps using paeonol and ethyl formate as starting materials. The reaction was followed by Heck coupling reaction and Sonogashira coupling reaction respectively The target compound with double bond and triple bond substituent at 3 position was obtained. The 3’- or 4’-amino compound was obtained by Suzuki coupling reaction and reacted with norcantharidin to obtain the target compound of amide. The product was characterized by 1HNMR, MS and IR The method determines the structure of the target compound. Human colon cancer cell line HCT116 and human hepatocellular carcinoma cell line SMMC7721 were selected as the experimental tumor strains, and the antitumor activity in vitro was determined by using curcumin and soybean isoflavone as positive control. Results The 17 target compounds were designed and synthesized in vitro. The compounds 7b and 7e showed good activity in comparison with that of the reference substance curcumin, which was significantly better than the IC50 value of the control sample soy isoflavone. Conclusion The insertion of double or triple bonds between benzopyrone and its 3-substituted phenyl group, ester group and hydroxymethyl group will not decrease the antitumor activity of the target compound and may increase its antitumor activity. However, Amidation of the 3’- or 4’-amino group of flavonoids with norcantharidin appears to be of little help in increasing its anti-tumor activity.