Total synthesis of phenanthroindolizidine alkaloids (±)-antofine, (±)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity
Public Deposited- Creator
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Su, Chung Ren
- Other Affiliation: National Cheng Kung University
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Damu, Amooru G.
- Other Affiliation: National Cheng Kung University
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Chiang, Po Cheng
- University of North Carolina at Chapel Hill
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Bastow, Kenneth F.
- University of North Carolina at Chapel Hill
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Morris-Natschke, Susan L.
- University of North Carolina at Chapel Hill
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Lee, Kuo Hsiung
- University of North Carolina at Chapel Hill
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Wu, Tian Shung
- Other Affiliation: National Cheng Kung University
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Su, Chung Ren
- Abstract
- Due to their limited natural abundance and significant biochemical effects, we synthesized the alkaloids (±)-antofine (1a), (±)-deoxypergularinine (1b), and their dehydro congeners (2 and 3) starting from the corresponding phenanthrene-9-carboxaldehydes. We also evaluated their in vitro cytotoxic activity. Compounds 1a and 1b showed significant potency against various human tumor cell lines, including a drug-resistant variant, with EC50 values ranging from 0.16–16 ng/mL. Structure–activity correlations of these alkaloids and some of their synthetic intermediates were also ascertained. The non-planar structure between the two major moieties, phenanthrene and indolizidine, plays a crucial role in the cytotoxic activity of phenanthroindolizidines. Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom (1b).
- Date of publication
- 2008
- Keyword
- Total synthesis
- In vitro
- Lignée cellulaire
- Racemic
- Antofine
- Glande mammaire
- Homme
- Cellule tumorale
- Alkaloid
- Tumor cell
- Mammary gland
- Human
- Lignée KB
- Synthèse chimique
- Racémique
- Cell line
- Chemical synthesis
- Deoxypergularinine
- Cytotoxic activity
- Phenanthroindolizidine alkaloids
- Cytotoxicity
- Poumon
- Biological activity
- Epiderme
- Epidermis
- Lung
- KB cell line
- DOI
- Identifier
- PMCID: PMC2577820
- Onescience id: dc946d2ea1a1fb7a0f2a9a8294c68501b8e1fbbc
- Publisher DOI: https://doi.org/10.1016/j.bmc.2008.04.032
- PMID: 18456501
- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- Bioorganic & Medicinal Chemistry
- Journal volume
- 16
- Journal issue
- 11
- Language
- English
- ISSN
- 0968-0896
- 1464-3391
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