Active Carbohydrate Research Institute, Chongqing Key Laboratory of Inorganic Functional Materials, Chongqing Normal University, Chongqing 401331, China.
Active Carbohydrate Research Institute, Chongqing Key Laboratory of Inorganic Functional Materials, Chongqing Normal University, Chongqing 401331, China.
Bioorg Med Chem. 2018 Nov 1;26(20):5578-5581. doi: 10.1016/j.bmc.2018.10.005. Epub 2018 Oct 9.
Epothilones are the 16-membered macrolide compounds, exhibit microtubule-promoting activity, have the same anti-tumor mechanism as paclitaxel, and are expected to be the ideal substitutes for paclitaxel. However, natural epothilone compounds have been found to have disadvantages such as high toxicity in vivo, poor selectivity to tumor cells, and susceptibility to drug resistance. Herein, epothilone B was synthesized by fermentation, and it was galactosylated by chemical method. The toxicity in vitro of epothilone B and its galactosylated derivative was investigated by the MTT method. The anticancer activity evaluation in vitro was performed using a method similar to the antibody-directed enzyme-prodrug therapy (ADEPT) method. It indicated that the ratio of cytotoxicity between the free epothilone B and the galactosylated epothilone B was about 150. This would lay the foundation for the targeted treatment of cancer with epothilone glycosides.
埃坡霉素是 16 元大环内酯类化合物，具有微管促进活性，与紫杉醇具有相同的抗肿瘤机制，有望成为紫杉醇的理想替代品。然而，天然埃坡霉素化合物存在体内毒性高、对肿瘤细胞选择性差、易产生耐药性等缺点。本研究通过发酵合成埃坡霉素 B，并通过化学方法对其进行半乳糖化。采用 MTT 法研究了埃坡霉素 B 及其半乳糖化衍生物的体外毒性，采用类似抗体导向酶前药治疗（ADEPT）的方法进行体外抗癌活性评价。结果表明，游离埃坡霉素 B 与半乳糖化埃坡霉素 B 的细胞毒性比值约为 150。这为埃坡霉素糖苷的靶向癌症治疗奠定了基础。
