Probing Anti-Leukemic Metabolites from Marine-Derived <i>Streptomyces</i> 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
Affiliations
You-Ying Chen
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung City 80424, Taiwan
Lo-Yun Chen
Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Po-Jen Chen
Department of Medical Research, E-Da Hospital, Kaohsiung City 82445, Taiwan
Mohamed El-Shazly
Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo 11566, Egypt
Bo-Rong Peng
National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan
Yu-Cheng Chen
Sepsis Research Center, Research Center of Tropical Medicine and Infectious Disease, Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Chun-Han Su
Department of Food Science, College of Human Ecology, Fu Jen Catholic University, New Taipei City 24205, Taiwan
Jui-Hsin Su
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung City 80424, Taiwan
Ping-Jyun Sung
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung City 80424, Taiwan
Pei-Tzu Yen
Department of Chinese Medicine, Sin-Lau Hospital, Tainan 70142, Taiwan
Lung-Shuo Wang
Department of Chinese Medicine, Sin-Lau Hospital, Tainan 70142, Taiwan
Kuei-Hung Lai
Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
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.
