194874-06-1

Usage

Uses

Used in Anticancer Applications:
Apoptolidin is used as an anticancer agent for its ability to induce apoptotic cell death in a variety of cancer cell lines. It has shown particular effectiveness against rat glial cells transformed with the adenovirus E1A oncogene (IC50 = 11 ng/ml) and is considered one of the most selective cytotoxic agents tested by the NCI. The compound's apoptotic activity is thought to be primarily due to its inhibition of F0F1-ATPase, although a secondary mechanism of action may also be involved.
Used in Drug Development and Research:
Apoptolidin is used as a research tool in the development of new cancer treatments. Its unique mechanism of action and selectivity for cancer cells make it an attractive candidate for further study and potential incorporation into novel therapeutic strategies. Researchers can utilize Apoptolidin to better understand the underlying processes of apoptosis and cancer cell death, which may lead to the discovery of new targets and treatments for various types of cancer.
Used in Drug Delivery Systems:
Similar to Gallotannin, Apoptolidin's potential applications can be enhanced through the development of novel drug delivery systems. These systems could improve the delivery, bioavailability, and therapeutic outcomes of Apoptolidin by employing various organic and metallic nanoparticles as carriers. This approach may help overcome any limitations associated with the compound's current formulation and increase its overall efficacy against cancer cells.

References

1) Kim et al. (1997), Apoptolidin, a new apoptosis inducer in transformed cells from Nocardiopsis sp.; J. Antibiot. (Tokyo), 50 628 2) Salomon et al. (2001), Apoptolidin, a selective cytotoxic agent, is an inhibitor of F0F1-ATPase; Chem. Biol., 8 71 3) Wender et al. (2006), Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues; Org. Lett., 8 589

Upstream product

• 795290-14-1 4'''-O-tert-butyldimethylsilyl-21-O-methyl-23O,2'O,3'O,3''O-tetrakis(triethylsilyl)apoptolidin A 
• 476647-30-0 isoapoptolidin A 
• 502156-06-1 apoptolidin-C₂₁-methyl ketal 

Downstream Products

• 476647-30-0 isoapoptolidin A 

Relevant academic research and scientific papers

Isoapoptolidin: structure and activity of the ring-expanded isomer of apoptolidin.

[formula: see text] Apoptolidin (1) is a novel oncolytic lead that induces apoptosis in transformed cell lines with exceptional selectivity. We report the isolation and characterization of a ring-expanded macrolide isomer of apoptolidin: isoapoptolidin (2). The solution conformation of isoapoptolidin is described. The rate of isomerization was measured under biologically relevant conditions and found to approach equilibrium within the time frame of most cell-based assays. Isoapoptolidin's ability to inhibit mitochondrial F0F1-ATPase is over 10-fold less than that of apoptolidin.

Apoptolidin A: Total synthesis and partially glycosylated analogues

The total synthesis of apoptolidin A is described employing an early glycosylation strategy. Strategic disconnections were chosen between C11-C12 (cross-coupling) and C19O-C1 (macrocyclization). The cis-selective glycosylation at C9-OH was achieved with the new SIBA protective group at O2/O3 of the L-glucose residue. Auxiliary substitutents at the 2-position of the 2-deoxy sugars were applied to form selectively the glycosidic linkages of the C27 disaccharide. The cross-coupling of the glycosylated northern half with the glycosylated southern half was achieved with Cu1-thiophene carboxylate. The macrocyclization of a trihydroxy carboxylic acid produced the 20-membered macrolide selectively. H2SiF6 was suitable for the final deprotection of the silyl ethers and the conversion of the C21 methylketal into the hemiketal. The synthetic flexibility of the approach was proven by the synthesis of some glycovariants.

Total synthesis of apoptolidin: Part 2. Coupling of key building blocks and completion of the synthesis

No less than 30 stereogenic elements, a highly unsaturated 20-membered macrocyclic system, four carbohydrate units, and unique biological activity, make the natural occurring apoptolidin (1) a challenging synthetic target. The retrosynthetic analysis reve