Bioactive staurosporine derivatives from the Streptomyces sp. NB-A13

Biao Zhou; Zhi-Juan Hu; Hao-Jian Zhang; Jia-Qi Li; Wan-Jing Ding; Zhong-Jun Ma

doi:10.1016/j.bioorg.2018.09.016

Bioactive staurosporine derivatives from the Streptomyces sp. NB-A13

Bioorg Chem. 2019 Feb:82:33-40. doi: 10.1016/j.bioorg.2018.09.016. Epub 2018 Sep 21.

Authors

Biao Zhou¹, Zhi-Juan Hu¹, Hao-Jian Zhang¹, Jia-Qi Li¹, Wan-Jing Ding¹, Zhong-Jun Ma²

Affiliations

¹ Institute of Marine Biology, Ocean College, Zhejiang University, No. 1 Zheda Rd., Zhoushan 316021, People's Republic of China.
² Institute of Marine Biology, Ocean College, Zhejiang University, No. 1 Zheda Rd., Zhoushan 316021, People's Republic of China. Electronic address: mazj@zju.edu.cn.

PMID: 30268972
DOI: 10.1016/j.bioorg.2018.09.016

Abstract

Six new (1-6) and nine known (7-15) staurosporine derivatives were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. NB-A13. The structures of the new staurosporine derivatives were established by extensive spectroscopic data interpretation. The absolute configurations of 1 and 2 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. All of these compounds were screened for their cytotoxic activities against PC-3 and SW-620 cell lines. Compound 7 exhibited stronger inhibitory activity against SW-620 cell lines than the positive control staurosporine (25.10 nM), with IC₅₀ values of 9.99 nM. Moreover, compounds 1-5, 8-13 and 15 also showed significant cytotoxicities with IC₅₀ values ranging from 0.02 to 16.60 μM, while 6 exhibited no cytotoxic potency. Additionally, compounds 1-7 were also tested for enzyme inhibition activities of Protein kinase C theta (PKC-θ), and showed activity with IC₅₀ values ranging from 0.06 to 9.43 μM except for compound 6, which has no inhibition activity.

Keywords: Cytotoxicity; PKC-θ inhibitor; Staurosporine derivatives.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Protein Kinase C-theta / antagonists & inhibitors
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / isolation & purification
Protein Kinase Inhibitors / pharmacology*
Staurosporine / analogs & derivatives*
Staurosporine / isolation & purification
Staurosporine / pharmacology*
Stereoisomerism
Streptomyces / chemistry*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
PRKCQ protein, human
Protein Kinase C-theta
Staurosporine