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Kristmundsdóttir, T. et al.

Kristmundsdóttir, Jónsdóttir, Ogmundsdóttir, Ingólfsdóttir,

Solubilization of poorly soluble lichen metabolites for biological testing on cell lines.

The depside atranorin and depsidone fumarprotocetraric acid, isolated from the lichens Stereocaulon alpinum and Cetraria islandica, respectively, were chosen as prototypes for poorly soluble natural compounds in an effort to facilitate testing in pharmacological models. Solubilizing agents previously identified as being non-toxic towards a malignant leukemic (K-562) cell line and suitable for testing of anti-proliferative activity of the dibenzofuran lichen metabolite (+)-usnic acid were used in solubilization studies of the depside and depsidone. Cyclodextrin derivatives were found to be most suitable for solubilizing the lichen compounds, the greatest rise in solubility being witnessed for fumarprotocetraric acid, increasing almost 300-fold from 0.03 mg/ml in water to 8.98 mg/ml in 10% 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). Subsequently, the lichen compounds, including (+)-usnic acid, were solubilized in 10% HPbetaCD and tested for effects on three malignant human cell lines; T-47D (breast), Panc-1 (pancreas) and PC-3 (prostate) in a standard proliferation assay. Atranorin and fumarprotocetraric acid did not exhibit anti-proliferative effects but usnic acid was active against all test cell lines with EC50 values of 4.3-8.2 microg/ml. The non-toxic solubilizing agents used in this study could prove useful for pharmacological testing of other poorly soluble natural products.[1]

References

Solubilization of poorly soluble lichen metabolites for biological testing on cell lines. Kristmundsdóttir, T., Jónsdóttir, E., Ogmundsdóttir, H.M., Ingólfsdóttir, K. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. (2005) [Pubmed]

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