Download Short Note No. 128/2013 applications in natural product research

Short Note No. 128/2013
Sepacore impact in anticancer drug development – recent
applications in natural product research
Sepacore X50, Sepacore X10, Sepacore Purification Systems
1. Introduction
On the one hand, the road towards a new effective
anticancer drug is long, bumpy, hidden, curvy,
potholed and above all the toll is very, very high. On
the other hand, the end of the road usually ends in the
land of plenty. The market for anti-cancer products is
predicted to grow from $54 billion in 2009 to $75 billion
in 2015 and is deemed to be the most lucrative
therapy sector. [1]
using different gradients yielded 141 mg of
damnacanthal a compound that could be of interest for
human pancreatic cancer treatment. [4]
Normally, the compounds are identified and
characterized by combined MS, IR and NMR analysis.
However, only one of 5000 drug candiates finally
masters the road. [2] In addition, identification of drug
candidates itself usually involves years of reserach.
So far, about 50 % of the anticancer drugs were
discoverd in natural products such as medicinal plants
or marine organisms. [3] Here, we selectively highlight
recent research on finding anticancer drug canditates
from natural origin using Sepacore for product
isolation.
2. Product isolation
In a first step in the hunt for new molecules, the
sample is extracted. Such a sample could be coral
sponges as shown in Figure 1. This step is crucial
since the solvent chosen for the extraction affects the
selection of the stationary phase for downstream
chromatography processes and of course defines
which compounds can be dissolved to the mixture.
Aqueous extracts, for example, cannot be separated
with normal silica. One needs reverse phase
stationary material as C-18 or diol substitiuted silica.
Figure 2. Chromatographic isolation pathway (bold line) for
damnacanthal, elucidated by Dibwe et al. [4]
Another successful isolation of potential drug
candidates using Sepacore was recently published by
Smitha et al. [5] Smitha and coworkers isolated
Prunolide A from ascidian Synoicum found in the
Indian Ocean, and which showed activity against
breast cancer cells at low concentrations.
In further phytochemical studies using the Sepacore
system new compounds were identified, however, no
or inconclusive cytotoxicity was observed. [6]
3. Sepacore impact
To rapidly identify drug candidates the compounds
need to be isolated as efficiently as possible.
Compared
to
traditional
hydrostatic
column
chromatography employing Sepacore equipped with a
state of the art UV/VIS or/and ELSD sucessfully
minimized the separation process time. As shown by
the researches cited above, the Sepacore can play a
key role to speed-up chromatographic processes of
natural extract separation towards new, highly desired
anticancer drugs.
4. References
Figure 1. A selection of coral sponges collected and then
separated employing the Sepacore by the Mauritius
Oceanography Institute (MOI).
After sampling, extraction, filtration and concentration
by evaporation under vaccum, the crude sample
mixture is separated into its components.
Usually, the first separation by medium pressure liquid
chromatography (MPLC) roughly devides the extract
into fractions of different polarities. To isolate a single
compound out of a mixture further separation steps by
MPLC are needed, often followed by preparative high
pressure liquid chromatography (HPLC).
In Figure, 2 a typical isolation pathway, elucidated by
Dibwe et al, is shown. [4] In their work a chloroform
extract (dry mass of 5.85 g) of G. huillensis, a
Congolese medical plant, was split into its
components. A three step normal phase separation
[1] www.swissinfo.ch/eng/science_technology/Drug_d
evelopment_s_road_gets_longer.html?cid=35210626
[2] www.swissinfo.ch/eng/science_technology/The_bu
siness_of_cancer_research.html?cid=35210166
[3] J. Mann, Nature Reviews, 2, 143, 2002.
[4] D. F. Dibwe et al, Phytother. Res., 26, 12, 1920–
1926, 2012.
[5] D. Smitha et al, Nat Prod Res, published online,
DOI:10.1080/14786419.2013.827194, 2013.
[6] G.-Q. Wang et al, J. Asian Nat Prod Res, published
online, DOI:10.1080/10286020.2013.824429, 2013.;
Y. Gao et al., Nat Prod Bioprospect 2, 2, 65-69,
2012. ; Y.-L. Li, Phytochemistry, 81, 159–164, 2012.