Fluorescent image-based high-content screening of extracts of natural resources for cell cycle inhibitors and identification of a new sesquiterpene quinone from the sponge, Dactylospongia metachromia
Autor: | Remy E. P. Mangindaan, Yuki Hitora, Fitje Losung, Koyo Honda, Ai Sejiyama, Sachiko Tsukamoto, Yuji Ise |
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Rok vydání: | 2020 |
Předmět: |
Cell Survival
Chemical structure Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Antineoplastic Agents Sesquiterpene 01 natural sciences Biochemistry HeLa chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Tumor Cells Cultured Animals Humans Molecular Biology Cell Proliferation Biological Products Natural product biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Cell Cycle Optical Imaging Quinones Cell cycle biology.organism_classification 0104 chemical sciences Quinone Porifera 010404 medicinal & biomolecular chemistry chemistry High-content screening Molecular Medicine Drug Screening Assays Antitumor Sesquiterpenes Bacteria |
Zdroj: | Bioorganicmedicinal chemistry. 31 |
ISSN: | 1464-3391 |
Popis: | Natural products are important sources for drug development. Discovery of natural products that inhibit cell cycle progression significantly contributes to the progress of cancer biology and the development of new antitumor agents. In this study, cell cycle inhibitory activity was evaluated with our extract library of natural resources, including marine invertebrates, fungi, and bacteria, using HeLa/Fucci2 cells which allow classification of the cell cycle phases of living cells. Screening of the extract library revealed that the extract of the marine sponge Dactylospongia metachromia inhibited cell cycle progression at S/G2/M phases. Bioassay-guided fractionation afforded a new sesquiterpene quinone, neoisosmenospongine (1), and four known compounds, nakijiquinone I, N, and Q (2-4) and (-)-dictyoceratin-C (5). The chemical structure of 1 was elucidated by interpretating the NMR and mass spectroscopic data, and the absolute configuration was determined by comparison of the experimental and calculated ECD spectra. Fluorescent imaging of HeLa/Fucci2 cells revealed that 1-4 inhibited the cell cycle progression at S/G2/M phases. This study demonstrated that fluorescent image-based high-content screening using HeLa/Fucci2 cells is an effective approach for isolating cell cycle inhibitors from natural resources. |
Databáze: | OpenAIRE |
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