In serum free buffer solutions, curcumin was observed to decompose in a pH-dependent manner, with faster reactions at neutral-basic conditions.

Curcumin showed greater stability in cell culture medium containing 10% fetal calf serum and in human blood.

Trans-6-(4'-hydroxy-3'-methoxyphenyl)-2,4-dioxo-5-hexanalwas predicted as the major degradation product.

Vanillin, ferulic acid, feruloyl methane were the minor degradation products, with vanillin increasing with the time of incubation.

The differential physical properties of the naturally occurring curcuminoids and selected derivatives was explained in a study which investigated intramolecular and intermolecular hydrogen bond formation in these compounds using absorption and emission properties.

The authors observed intermolecular hydrogen bond formation in both the ground state and the excited state of the curcuminoids possessing a phenolic group.

The phenolic groups in curcumin showed hydrogen bond acceptor properties, while those in bisdemethoxycurcumin acted as hydrogen bond donors, explaining their differential polarity of these curcuminoids when mixed with various alcohols.

A recent study compared the antiinflammatory activity of synthetic derivatives with that of the parent compounds.

The authors used the carrageenan edema test in the hind paw of rats to compare the antiinflammatory effects of various derivatives.

Several symmetrically substituted curcumin derivatives were found to possess potent antiinflammatory action, particularly those having a combination of 4-hydroxy groups and 3,5-di-(lower) alkyl groups.

The authors of this study found that the para hydroxy groups in curcumin are important for antiinflammatory activity.

This activity is enhanced if the meta positions are occupied by alkyl groups concurrently.

As the methyl derivatives were more active than the ethyl and tert-butyl derivatives, it was suggested that steric hindrance affects biological activity.

The general structure of these derivatives is represented below:

Eight synthetic curcuminoids were investigated for their cytotoxic and tumoricidal activities as well as their free radical scavenging activity.13 In experiments with cultured L929 cells, all these compounds were found to be cytotoxic. The LD50 value was 1 mg/ml (3.9 - 2.5 mM). Veratryl curcuminoid and salicyl curcuminoid functioned as antitumor agents, increasing the life span of animals by 100.6 and 86.9% respectively. Curcuminoids with a free hydroxyl group on the phenyl ring, such as the salicyl compound were found to be more active, while compounds which did not have the hydroxyl group had lower in vitro cytotoxic activity. However, all compounds showed comparable in vivo activity.

The relationship between antitumor activity and molecular structure of curcuminoids has been explored.14 The effect of curcuminoids and cyclocurcumin (Cyclocur) on the proliferation of MCF-7 human breast tumor cells was studied. Curcuminoids appeared to be potent inhibitors, whereas Cyclocur was less inhibitory. It was observed that Curcumin exerts a cytostatic effect at the proliferation stage. The presence of the diketone moiety in the curcumin molecule seems to be essential for the inhibitory activity.

Effects of new complex curcuminoids (cassumunin A and cassumunin B) isolated from tropical ginger, Zingiber cassumunar, were examined in dissociated rat thymocytes suffering from oxidative stress induced by 3 mM hydrogen. The effects were compared with those of curcumin, whose chemical structure is included in those of cassumunins A and B. Pretreatment of rat thymocytes with the respective cassumunins at concentrations ranging from 100 nM to 3 mM dose-dependently prevented the hydrogen peroxide-induced decrease in cell viability. The potencies of cassumunins A and B this regard, were greater than that of curcumin. The authors postulate that cassumunins A and B may possess a potent protective action on living cells suffering from oxidative stress. Subsequently, a synthetic method for cassumunins with o-vanillin as starting material was developed. In an in vitro study on a rat thymocyte system, in which oxidative cell death was induced by hydrogen peroxide, the synthetic cassumunins showed stronger protective activity than curcumin16.

5'-n-alkyl substituted curcumin derivatives were found to be more effective than curcumin in inhibiting lipid peroxidation. To elucidate the roles of the 5'-n-alkyl chains in the protective action of the compounds against oxidative stress, experiments were performed on rat thymocytes in which oxidative stress was induced using hydrogen peroxide. The inhibitory action of the 5'-n-alkylated curcumins on lipid peroxidation increased as the length of hydrocarbon chains in them increased. Among the various derivatives of this type, 5'-n-C3H7 curcumin had the greatest protective action because it had the greatest permeation into the cells17.

A recent review summarizes currently available data on the chemopreventive efficacies, proposed mechanisms of action and relationships between activities and structures of several natural products. Featured products include vitamin D, calcium, dehydroepidandrosterone, coenzyme Q10, celery seed oil, parsley leaf oil, sulforaphane, isoflavonoids, lignans, protease inhibitors, tea polyphenols, curcumin, and polysaccharides from Acanthopanax genus18.

A study reporting the differential activities of Curcuminoids and tetrahydrocurcumin aginst tumor-promoter induced reactive oxygen species both in vitro and in vivo eas published12(a). Curcumin, tetrahydrocurcumin (THC) and dihydroxytetrahydrocurcumin (DHTHC) exhibited significant of reactive oxygen species inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced generation in differentiated HL-60 cells. However, the inhibitory activity of THC was weaker than that of curcumin. This tendency was the inverse of the results of previous studies on in vitro antioxidant activity against lipid peroxidation. THC exhibited much weaker inhibition of intracellular peroxide formation than curcumin, suggesting that this inhibition might be attributable to the inhibition of reactive oxygen species. The inhibitory effects of curcuminoids on TPA-induced H2O2 formation in female mouse skin were further examined using the double-TPA-application model (inducing migration of inflammatory cells as well as peroxide production). Coadministrations of curcumin with either first or second TPA treatment significantly inhibited H2O2 formation. However, THC was observed to show weaker inhibitory activities than curcumin in bioassays related to tumor promotion, Epstein-Barr virus activation. The authors concluded that curcuminoids significantly suppress TPA-induced oxidative stress via both interference with infiltration of leukocytes into the inflammatory regions and inhibition of their activation.