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

Abstract

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.

Capnellenes from Capnella imbricata: Deciphering Their Anti-Inflammatory-Associated Chemical Features

“…The Backlund group introduced ChemGPS-NP, a model based on principle component analysis (PCA) for analyzing natural products in 2007 [ 10 , 11 ]. They subsequently established an online system in 2009 that offers the analysis of eight principle components (PCs).…”

“…In this study, we utilized ChemGPS-NP to establish the chemical relationships between capnellenes discussed in our present research and those mentioned in our previous publications [2] that possess anti-inflammatory activity. We mapped a total of 14 capnellene sesquiterpenes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) in a chemical space using PC score predictions from the online tool ChemGPS-NPWeb (Figure 5). Additionally, we retrieved previously disclosed inhibitors that target inflammation-related proteins iNOS from the ChEMBL online database and included them in the analysis.…”

Analysis of Secondary Metabolite Synthesis Potential of Streptomyces fradiae sf106 Based on the Whole Genome and Non-Target Metabolomics and Exploration of the Biosynthesis of Tylosin

“…The widespread use of antibiotics, such as tetracycline, cephalosporins, and erythromycin, has revolutionized medical treatment and agricultural practices. This underscores the critical role of antibiotics and natural products, making the discovery of new secondary metabolites a research priority [50][51][52]. Despite advances, many metabolites remain undiscovered or underutilized.…”