Curcuminoids, curcuminoid like-compounds and ferulic acid derivates : Their synthesis, purification, characterization, radical scavenging capacity and complexation with cyclodextrins

by Ravinder Singh

Institution: University of Oslo
Year: 1000
Keywords: kompleksering cyclodextrin aktivitet curcuminoider fase løselighet UV-spektroskopi; VDP::568
Record ID: 1295087
Full text PDF: https://www.duo.uio.no/handle/10852/12212


ABSTRACT The curcuminoids belong to the group diarylheptanoids and are the colouring principles found in the rhizomes of the plant Curcuma longa L. (Zingiberaceae). The curcuminoids have shown unique properties and many pharmacological effects. There is a great interest in their antioxidant effect and also in their anticancer effect. They are also non toxic in high doses. Because of this, they have a great potential as future drugs or as model substances for treatment of various diseases. Before this can be reality one has to make a useful pharmaceutical formulation of the curcuminoids. Unfortunately there have been some difficulties doing this. The curcuminoids have very low water solubility, especially at acidic pH. They are also quite unstable, susceptible to both hydrolysis at neutral to alkaline pH and to photochemical degradation. This might also explain their low bioavailability. Cyclodextrins (CDs) are cyclic oligosaccharides, containing a relative hydrophobic central cavity and a hydrophilic outer surface. They can increase the aqueous solubility of compounds by forming inclusion complexes. It has also been shown that they can increase solubility by forming non-inclusion complexes. HydroxypropylãCD (HPãCD) and hydroxypropylâCD (HPâCD) are reported to be fairly non-toxic. They have also been shown to improve hydrolytic stability and solubility of the curcuminoids. However, complexation to CDs has shown a photochemically destabilizing effect on some of the curucminoids. Further, it is not known whether the cucuminoids form a 1:1 or a 1:2 complex stoichiometry (compound:CD) with the CDs. In the present work, curcumin, bisdemethoxycurcumin, diketone (a half curcumin), ethylferulate and acetogalactosidebromide were synthesized, purified and characterized (by melting point in open capillaries, DSC, UV-spectrum, IR spectrum, NMR spectrum). The acetogalactosidebromide should be used to make the digalactoside of curcumin. It was expected that this compound would have a high aqueous solubility. However, the synthesis failed. It was assumed that the solvent used in the synthesis, pyridine, degraded acetogalactosidebromide and curcumin before they got a chance to form the digalactoside. Then the DPPH∙ radical scavenging capacity was investigated for the four remaining compounds. Curcumin, diketone and ethylferulate had nearly quantitative reactions with the free radical, showing the importance of the phenolic group, the methoxy group next to the phenolic group and the conjugated double bond for the radical scavenging capacity. The investigation also showed that the two parts of curcumin scavenge radicals independently. The diketone moiety did not however, prove to be very important for the radical scavenging capacity. The unidentified peak in the HPLC chromatograms of curcumin, bisdemethoxycurcumin and diketone was also investigated by UV-Vis spectroscopy and HPLC chromatography. The peak could not be identified, however, the presence of the peak seems to be related to the presence of the…