Abstract |
(-)- Exiguolide (1), isolated from the marine sponge Geodia exigua, has been shown to inhibit the growth of the A549 human lung adenocarcinoma and NCI-H460 human lung large cell carcinoma cells in vitro. In this study, we synthesized structural analogues of 1 to explore its skeletal structure-activity relationships and found that the C18 methyl group and the configuration of the C16-C17 double bond of 1 are important for the potent antiproliferative activity. Furthermore, we prepared a series of side-chain analogues of 1 by diversification of a late-stage intermediate of our total synthesis, and found that the triene side chain of 1 could be modified to some extent without significant loss of activity, provided a Lewis basic heteroatom is placed at the terminus.
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Authors | Haruhiko Fuwa, Kana Mizunuma, Makoto Sasaki, Takaya Suzuki, Hiroshi Kubo |
Journal | Organic & biomolecular chemistry
(Org Biomol Chem)
Vol. 11
Issue 21
Pg. 3442-50
(Jun 07 2013)
ISSN: 1477-0539 [Electronic] England |
PMID | 23538720
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Macrolides
- exiguolide
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Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Humans
- Macrolides
(chemical synthesis, chemistry, pharmacology)
- Magnetic Resonance Spectroscopy
- Molecular Structure
- Neoplasms
(drug therapy)
- Structure-Activity Relationship
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