2. Academic Validation
  3. 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

  • J Nat Prod. 2018 Aug 24;81(8):1745-1751. doi: 10.1021/acs.jnatprod.8b00103.
Fei Xiao 1,  Huayue Li 1 2,  Mingyuan Xu 1,  Tong Li 1,  Ju Wang 3,  Chaomin Sun 2 3,  Kui Hong 4,  Wenli Li 1 2
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy , Ocean University of China , Qingdao 266003 , People's Republic of China.
  • 2 Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology , Qingdao 266000 , People's Republic of China.
  • 3 Key Laboratory of Experimental Marine Biology , Institute of Oceanology, Chinese Academy of Sciences , Qingdao 266071 , People's Republic of China.
  • 4 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education of China, School of Pharmaceutical Sciences , Wuhan University , Wuhan 430071 , People's Republic of China.
PMID: 30106291 DOI: 10.1021/acs.jnatprod.8b00103
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 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.

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