Autophagy-modulating aminosteroids isolated from the sponge Cliona celata
Robert A Keyzers1, Julie Daoust, Michael T Davies-Coleman
1Department of Chemistry and Earth & Ocean Sciences, University of British Columbia, Vancouver, BC, Canada.
Organic Letters
|June 17, 2008
Summary
Four new aminosteroids, Clionamines A-D, were discovered in the sponge Cliona celata. These compounds modulate autophagy, with Clionamine D featuring a unique spiro bislactone side chain.
Area of Science:
- Marine natural products chemistry
- Chemical biology
- Drug discovery
Background:
- Marine sponges are a rich source of novel bioactive compounds.
- Autophagy is a crucial cellular process implicated in various diseases.
- Aminosteroids represent a class of compounds with diverse biological activities.
Purpose of the Study:
- To isolate and characterize new aminosteroids from the sponge Cliona celata.
- To investigate the effects of these compounds on autophagy.
- To explore the structural novelty of the isolated compounds.
Main Methods:
- Isolation and purification of compounds using chromatographic techniques.
- Structure elucidation using spectroscopic methods (NMR, MS).
- Autophagy modulation assays in cellular models.
Main Results:
- Four new aminosteroids, Clionamines A-D, were identified.
- Clionamines A-D were found to modulate autophagy.
- Clionamine D possesses a unique spiro bislactone side chain, a previously unreported structural motif.
Conclusions:
- Cliona celata harbors novel aminosteroids with autophagy-modulating properties.
- The discovery of Clionamine D expands the structural diversity of natural products.
- These findings may offer new avenues for therapeutic development targeting autophagy.
Related Concept Videos
Autophagy
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Delivery Pathways to the Lysosome
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Drugs that Stabilize Microtubules
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...


