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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells
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Evaluation of the cytotoxic activity of new jadomycin derivatives reveals the potential to improve its selectivity against tumor cells

机译：对新的霉素分子的细胞毒性活性的评估表明，有可能提高其对肿瘤细胞的选择性

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摘要

The jadomycins are a unique family of angucycline-derived antibiotics with interesting cytotoxic activities. In this work, six new jadomycin derivatives were produced in vivo by providing non-natural amino acids in fermentation media. They were further purified and identified by MS and NMR analyses. The cytotoxicities of these derivatives were evaluated against tumor cell lines MCF-7 and HCT116, as well as the normal human microvascular epithelial cells. The derivatives with alkyl side chains showed similar levels of cytotoxicity as jadomycin B and other known derivatives with nonpolar side chains, with IC 50 ranging from 1.3 to 10 M; but the activities are not selective as these compounds also showed similar levels of cytotoxicity toward the normal human microvascular epithelial cells in the same concentration range. For the first time, derivatives with amino side chains (jadomycin Orn and K) were prepared and evaluated. Significantly, jadomycin Orn showed differential activity against normal and tumor cell lines. This result points to a new direction to modify jadomycin structure. The insights on the structure-activity relationship of jadomycins will guide further efforts to generate new and improved jadomycin derivatives against tumor cells.
机译：佳霉素是具有独特的细胞毒性活性的独特的家族，其源于环霉素的抗生素。在这项工作中，通过在发酵培养基中提供非天然氨基酸，在体内产生了六种新的贾德霉素衍生物。它们被进一步纯化，并通过MS和NMR分析鉴定。评估了这些衍生物对肿瘤细胞系MCF-7和HCT116以及正常人微血管上皮细胞的细胞毒性。具有烷基侧链的衍生物显示出与杰霉素B和其他已知的具有非极性侧链的衍生物相似的细胞毒性水平，IC 50为1.3至10M。但活性不是选择性的，因为这些化合物在相同浓度范围内对正常人微血管上皮细胞也显示出相似的细胞毒性水平。首次制备并评估了具有氨基侧链的衍生物（鸟霉素Orn和K）。值得注意的是，贾德霉素Orn对正常和肿瘤细胞系表现出不同的活性。这一结果为修饰贾霉素的结构指明了新的方向。对贾德霉素的结构-活性关系的见解将指导进一步努力，以产生针对肿瘤细胞的新的和改良的贾德霉素衍生物。

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