抗癌药物埃博霉素的生产及工艺发展

Production and Process Development of Anticancer Drug Epothilone

埃博霉素(Epothilone)作为一类以大环内酯为中心体的具有抗癌活性的化合物,对乳腺癌及直肠癌等肿瘤细胞具有强烈的抑制作用。它的作用机制与紫杉醇十分相似,即通过诱导微管蛋白多聚体形成超稳定态,从而将有丝分裂阻止在G2-M期,由此达到抑制肿瘤细胞繁殖乃至诱导其死亡的目的,但它的抗肿瘤活性却是紫杉醇的10-1 000倍。并且埃博霉素作为一类细菌次级代谢产物,其可通过微生物大规模发酵生产的这一天然优势,也使得它不会像紫杉醇一样受到来源的限制。除此以外,埃博霉素相对简单的分子结构也使得其具有良好的化学结构修饰潜力,最重要的是,埃博霉素对一些已经产生耐药的肿瘤细胞也表现出了较高的活性。因此,其巨大的药用价值和市场潜力能够使之成为继紫杉醇之后的又一新型抗肿瘤药物,具有重要的应用价值。就埃博霉素的化学合成、生物合成、分离提取及如何提高埃博霉素的产量等方面的研究进展进行综述,从而使得初入本领域的研究者们对于埃博霉素的研究近况有一个大致的了解,并对其后期的研究思路起到一定的引导作用。

Epothilone is a class of macrolide-centered compounds with anticancer activity,and it has a strong inhibitory effect on breast cancer and rectal cancer.Its mechanism of action is very similar to the paclitaxel’s,that is,mitosis can be prevented at G2-M phase by inducing tubulin polymer to form superstable state,which can inhibit the proliferation of cancer cells and even induce their death.However,its antitumor activity is 10-1000 times higher than that of paclitaxel.As a secondary metabolite of bacteria,epothilone can be produced by microbial fermentation at a large scale,which makes it not restricted by sources like paclitaxel.In addition,because of its relatively simple molecular structure,there is a bright potential for epothilone to have chemical structural modification.Most importantly,epothilone has also shown high activity against some cancer cells that have developed drug resistance.Therefore,its huge medicinal value and market potential can make it a new type of anti-cancer drug after paclitaxel,thus is has an important application value.This paper reviews the research progress of chemical synthesis,biosynthesis,isolation and extraction of epothilone and how to improve the yield of epothilone,so that new researchers in this field have a general understanding of the recent research situation of epothilone,and it may play a guiding role in their later research ideas.