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Selective cytotoxicity of Pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds
Selective cytotoxicity of Pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds
- Source :
- Cancer Cell International, Vol 7, Iss 1, p 10 (2007)
- Publication Year :
- 2007
- Publisher :
- BMC, 2007.
-
Abstract
- Abstract Background Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton. Results Our results indicate that AMD5 has efficacy and selectivity similar to PST, albeit at a 10-fold increased concentration. Interestingly AMD4 lacks apoptotic activity. Conclusion Our results indicate that the phenanthridone skeleton in natural Amaryllidaceae alkaloids may be a significant common element for selectivity against cancer cells; furthermore, the configuration of the methoxy-side groups is responsible for higher binding affinity to the target protein/s thus making for a more efficient anti-cancer agent.
Details
- Language :
- English
- ISSN :
- 14752867
- Volume :
- 7
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cancer Cell International
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5ab1ff2f7dc34948a064c300a212cd9b
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/1475-2867-7-10