Staurosporine derivatives generated by pathway engineering in a heterologous host and their cytotoxic selectivity
Staurosporine derivatives generated by pathway engineering in a heterologous host and their cytotoxic selectivity
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异源宿主中通过途径工程产生的十字孢菌素衍生物及其细胞毒性选择性
DOI：
10.1021/acs.jnatprod.8b00103
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发表时间：
2018
影响因子：
5.1
通讯作者：
Wenli Li
中科院分区：
文献类型：
--
作者：
Fei Xiao;Huayue Li;Mingyuan Xu;Ju Wang;Chaomin Sun;Kui Hong;Wenli Li
Two new staurosporine derivatives, staurosporines M1 and M2 (4 and 5), in addition to five previously reported metabolites (1–3, 6, and 7), were generated by the heterologous expression of engineered spc gene clusters in Streptomyces coelicolor M1146. The structures of these derivatives were determined by a combination of spectroscopic methods and CD measurement. Compounds 1, 2, 4, and 5 showed effective activities against three tumor cell lines (HCT-116, K562, and Huh 7.5), and 3 was active against HCT-116 and K562 cells. In addition, compounds 3 and 5 showed undetectable toxicity up to 100 μM toward the normal hepatic cell line LO2. Based on the IC50 values, their structure and activity relationships are discussed.
