Title
Staurosporine Derivatives Generated by Pathway Engineering in a Heterologous Host and Their Cytotoxic Selectivity
Author
Fei Xiao, Huayue Li, Mingyuan Xu, Tong Li, Ju Wang, Chaomin Sun, Kui Hong, Wenli Li
Year
2018
Journal
Journal of Natural Products
Abstract
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 3and 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.
Instrument
J-715
Keywords
Circular dichroism, Absolute configuration, Natural products, Pharmaceutical