THE INFLUENCE OF POLYETHER SUBSTITUENTS ON BIOLOGICAL ACTIVITY OF CURCUMIN DERIVATIVES

Curcumin is reported as an anti proliferative and chemopreventive compound. However, it shows poor water solubility, low bioavailability, and rapid metabolism.. To address these problems, curcumin derivatives substituted with polyether chain were synthesised to improve the hydrophilicity of curcumin and thus its bioavailability. The biological activity of modified curcumin molecules were studied with human normal B-lymphocytes GM 14667 and human leukemia cells HL60 and covered: the denotation of IC50 values for each new compound with use of MTT test and the studies on apoptosis induction observed as morphological changes and the expression of apoptotic proteins, BAX, BCL-2 and survivin with use of Western Blot analysis. All effects were referenced to native curcumin. The derivatives with modified polyether chains number and the position of methoxy- groups were selected for further studies. As was shown, the solubility of the compound does not directly correlate with its cytotoxicity. The maintenance of the methoxy group in the meta position as well as the introduction of hydrophilic polyether chains but not the number of polyether chains may affect the cytotoxic activity of curcumin derivatives against cancer cells. Modifications of the curcumin molecule structure can determine its impact on the profile of pro or anti apoptotic proteins

Polyurethane Foam Rafts Supported In Vitro Cultures of Rindera graeca Roots for Enhanced Production of Rinderol, Potent Proapoptotic Naphthoquinone Compound

Unique phytochemical profile of plants belonging to Boraginaceae family provides a prolific resource of lipophilic pigments from the group of naphthoquinone derivatives. To overcome low compound content, the major obstacle of plant-based production, immobilization of Rindera graeca roots in in vitro cultures was implemented for efficient production of rinderol, novel furanonaphthoquinone derivative with anticancer properties. Chromatographic procedures revealed rinderol presence in extracts of all investigated root lines, derived both from root biomass and post-culture medium. Unexpectedly, in the second stage of the experiment, rinderol production was ceased in control, unmodified culture systems. On the contrary, roots immobilized on PUF rafts uniformly and stably produced rinderol, and its highest amount was noted for transformed root lines after 42 days of cultivation (222.98 ± 10.47 µg/flask). PUF occurred to be the main place of compound accumulation. Moreover, investigation of rinderol biological activity revealed its fast-acting cell death induction in HeLa cervical cancer cells at relatively low concentrations. Presented results revealed successful application of R. graeca roots immobilization on PUF rafts for production and in situ product removal of rinderol, novel lipophilic furanonaphthoquinone with suggested proapoptotic activity