Liu Hai-Xia, Huang Guo-Rui, Zhang Huan-Ming, Wu Jia-Rui, Yao Zhu-Jun
State Key Laboratory of Bioorganic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Bioorg Med Chem Lett. 2007 Jun 15;17(12):3426-30. doi: 10.1016/j.bmcl.2007.03.084. Epub 2007 Mar 30.
Annonaceous acetogenins are a large class of naturally occurring polyketides exhibiting potent anticancer activities. Based on our previous discovery of AA005, a multi-ether mimic of natural acetogenins having potent antitumor activities and significant selectivity between normal cells and cancer cells, a new series of mimics containing a terminal lactam were designed, synthesized and evaluated. Bioactivity study against cancer cells shows that the N-methylated lactam-containing compounds 3, 4, and 5 exhibit comparable potencies to that of AA005, as well as the similar selectivity to cancer cells. Hydrocarbon-length effects of N-alkyl were further explored through synthesizing derivatives 24-26, and application of this derivation protocol to the fluorescent labeling was also investigated.
番荔枝内酯是一大类天然存在的聚酮化合物，具有强大的抗癌活性。基于我们之前发现的AA005，一种具有强大抗肿瘤活性且在正常细胞和癌细胞之间具有显著选择性的天然番荔枝内酯的多醚模拟物，设计、合成并评估了一系列新的含有末端内酰胺的模拟物。针对癌细胞的生物活性研究表明，含N-甲基化内酰胺的化合物3、4和5表现出与AA005相当的效力，以及对癌细胞的类似选择性。通过合成衍生物24-26进一步探索了N-烷基的烃链长度效应，并研究了该衍生方案在荧光标记中的应用。
