Structure and Activity of Largazole, a Potent Antiproliferative Agent from the Floridian Marine Cyanobacterium Symploca sp.
Abstract
A novel cytotoxic cyclodepsipeptide, termed largazole ( 1 ), has been isolated from the marine cyanobacterium Symploca sp. collected in the Florida Keys. Its planar structure was elucidated by 1D and 2D NMR spectroscopy in conjunction with mass spectrometry. The absolute configuration of 1 was determined by chemical degradation followed by chiral HPLC analysis. Largazole ( 1 ) possesses densely assembled unusual structural features, including a rare 4-methylthiazoline linearly fused to a thiazole in its cyclic core and a hitherto undescribed 3-hydroxy-7-mercaptohept-4-enoic acid unit incorporated in an ester, thioester, and amide framework. Largazole ( 1 ) exhibits potent antiproliferative activity and preferentially targets cancer cells over nontransformed cells.
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- Authors
- Taori, K., Paul, V. J., & Luesch, H.
- Affiliations
- University of Florida (US)
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-01-19
- Volume
- 130
- Issue
- 6
- Pages
- 1806-1807
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2031598870
- Cited by
- 428
- References
- 12
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 16 · 2023: 19 · 2022: 20 · 2021: 24 · 2020: 33 · 2019: 25 · 2018: 19 · 2017: 25 · 2016: 24 · 2015: 33 · 2014: 29 · 2013: 24 · 2012: 24
- FWCI
- 19.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Smithsonian Digital Repository (Smithsonian Institution) (submittedVersion)
- Funders
- National Science Foundation
- National Oceanic and Atmospheric Administration
- Florida Sea Grant, University of Florida
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- largazole, Symploca, marine cyanobacteria, cyclodepsipeptides, cytotoxic natural products, antiproliferative activity, structure elucidation, absolute configuration, thiazole, anticancer agents, Florida Keys
- MeSH terms
- Cyanobacteria, Animals, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Epithelial Cells, Fibroblasts, Humans, Molecular Conformation, Magnetic Resonance Spectroscopy, Reference Standards, Mass Spectrometry, Thiazoles, NIH 3T3 Cells, Cell Line, Tumor, Depsipeptides, Cell Proliferation, Mice
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