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Biostructural features of additional jasplakinolide (jaspamide) analogues
Katharine R Watts1, Brandon I Morinaka, Taro Amagata
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, California 95064, United States.
Journal of Natural Products
|January 19, 2011
Summary
Marine sponges yield new jasplakinolide compounds that stabilize filamentous actin (F-actin). These cytotoxic molecules, including novel jasplakinolide V, disrupt microfilaments and show potential for cancer research.
Area of Science:
- Marine Natural Products Chemistry
- Chemical Biology
- Pharmacology
Background:
- Jasplakinolide (1), a cyclodepsipeptide from Jaspis splendens, stabilizes filamentous actin (F-actin) and acts as a cytotoxin.
- Previous studies identified jasplakinolides B (3) and E, prompting further investigation into Fijian J. splendens collections.
Purpose of the Study:
- To isolate and characterize new jasplakinolide analogues from Jaspis splendens.
- To evaluate the biological activity of these compounds in cancer cell line screens and microfilament disruption assays.
Main Methods:
- Isolation and structural elucidation of secondary metabolites from Jaspis splendens.
- Cytotoxicity screening using the National Cancer Institute's (NCI) 60 cell line panel.
- Phenotypic assays assessing microfilament disruption in HCT-116 and HeLa cells.
Main Results:
- Six known and four new jasplakinolide analogues were identified, including open-chain and modified β-tyrosine derivatives.
- Cytotoxic analogues, including jasplakinolide B (3), demonstrated microfilament disruption.
- The new compound jasplakinolide V (13) was selected for further NCI evaluation.
Conclusions:
- Reinvestigation of Jaspis splendens yielded diverse jasplakinolides with cytotoxic and F-actin-stabilizing properties.
- Phenotypic screens confirm microfilament modification as the mechanism of action for cytotoxic analogues.
- Jasplakinolide V represents a promising new candidate for cancer research and drug development.
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