State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Org Biomol Chem. 2022 Jan 26;20(4):870-876. doi: 10.1039/d1ob02292j.
Seventeen C20--alkyl/benzyl oxime derivatives were synthesized by a concise and effective method. Most of these derivatives showed tens to several hundred nanomolar IC values against HT-29 colorectal, HGC-27 gastric and MDA-MB-231 breast cancer cells, whose antiproliferative activity is 15-240 fold better than that of salinomycin. The C20-oxime etherified derivatives can coordinate potassium ions, and further adjust the cytosolic Ca concentrations in HT-29 cells. The significant improvement of the potency should be attributed to the better ion binding and transport ability of the modified derivatives. In addition, the C20--alkyl/benzyl oxime derivatives showed much better selectivity indexes (SI) than salinomycin, indicating that they present lower neurotoxic risk.
十七个 C20-烷基/苄基肟衍生物通过一种简洁有效的方法合成。这些衍生物对 HT-29 结肠直肠、HGC-27 胃和 MDA-MB-231 乳腺癌细胞的半数抑制浓度（IC）值在纳摩尔范围内，其增殖抑制活性比萨利霉素高 15-240 倍。C20-肟醚化衍生物可以与钾离子配位，并进一步调节 HT-29 细胞中的细胞溶质 Ca 浓度。活性的显著提高归因于修饰衍生物更好的离子结合和运输能力。此外，C20-烷基/苄基肟衍生物的选择性指数（SI）明显高于萨利霉素，表明它们的神经毒性风险较低。
