Probing Anti-Leukemic Metabolites from Marine-Derived Streptomyces sp. LY1209

You-Ying Chen, Lo-Yun Chen, Po-Jen Chen, Mohamed El-Shazly, Bo-Rong Peng, Yu-Cheng Chen, Chun-Han Su, Jui-Hsin Su, Ping-Jyun Sung, Pei-Tzu Yen, Lung-Shuo Wang, Kuei-Hung Lai

研究成果: 雜誌貢獻文章同行評審

摘要

The unmet need for specific anti-leukemic agents for the treatment of acute lymphoblastic leukemia led us to screen a variety of marine-derived bacteria. The fermentation broth extract of Streptomyces sp. LY1209 exhibited the most potent anti-proliferative effect against Molt 4 leukemia cells. A chromatographic anti-proliferative profiling approach was applied to characterize the metabolites with bioactive potential. Among all the metabolites, the major anti-leukemic constituents were staurosporine and a series of diketopiperazines (DKPs), including one novel and two known DKPs identified from nature for the first time. The structures of these compounds were identified using extensive spectroscopic analysis. The anti-proliferative potential of these metabolites against the Molt 4 cancer cell line was also determined. According to the in silico analysis utilizing a chemical global positioning system for natural products (ChemGPS-NP), it was suggested that these DKPs are potential anti-microtubule and alkylating agents, while staurosporine was proposed to be a tyrosine kinase inhibitor. Our findings not only identified a series of anti-proliferative metabolites, but also suggested a strategic workflow for the future discovery of natural product drug leads.
原文英語
期刊Metabolites
12
發行號4
DOIs
出版狀態已發佈 - 4月 2 2022

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