Naphthablins B and C, Meroterpenoids Identified from the Marine Sediment-Derived Streptomyces sp. CP26-58 Using HeLa Cell-Based Cytological Profiling

HeLa cell-based cytological profiling (CP) was applied to an extract library of marine sediment-derived actinomycetes to discover new cytotoxic secondary metabolites. Among the hit strains, Streptomyces sp. CP26-58 was selected for further investigation to identify its cytotoxic metabolites. CP reve...

Full description

Saved in:
Bibliographic Details
Published in:Journal of natural products (Washington, D.C.) D.C.), 2017-03, Vol.80 (3), p.684-691
Main Authors: Martucci, Hana, Campit, Scott E, Gee, Stephanie R, Bray, Walter M, Gokey, Trevor, Cada, A. King, Yen, Ten-Yang, Minoura, Katsuhiko, Guliaev, Anton B, Lokey, R. Scott, Amagata, Taro
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antineoplastic Agents - chemistry
Antineoplastic Agents - isolation & purification
Antineoplastic Agents - pharmacology
Geologic Sediments - chemistry
HeLa Cells
Humans
Inhibitory Concentration 50
Marine Biology
Molecular Structure
Naphthoquinones
Nuclear Magnetic Resonance, Biomolecular
Streptomyces - chemistry
Terpenes - chemistry
Terpenes - isolation & purification
Terpenes - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:HeLa cell-based cytological profiling (CP) was applied to an extract library of marine sediment-derived actinomycetes to discover new cytotoxic secondary metabolites. Among the hit strains, Streptomyces sp. CP26-58 was selected for further investigation to identify its cytotoxic metabolites. CP revealed that the known ionophore tetronasin (1) was responsible for the cytotoxic effect found in the extract. Furthermore, three naphthoquinone meroterpenoids, naphthablin A (2) and two new derivatives designated as naphthablins B (3) and C (4), were isolated from other cytotoxic fractions. The structures of the new compounds were elucidated based on analysis of their HRESIMS and comprehensive NMR data. The absolute configurations of the new compounds were deduced by simulating ECD spectra and calculating potential energies for the model compounds using density function theory (DFT) calculations. Compound 1 showed a significant cytotoxic effect against HeLa cells with an IC50 value of 0.23 μM, and CP successfully clustered 1 with calcium ionophores.
ISSN:0163-3864
1520-6025
DOI:10.1021/acs.jnatprod.6b00996