Three curcumin analogues viz., bisdemethoxy curcumin, monodemethoxy curcumin, and dimethoxycurcumin that differ at the phenolic substitution were synthesized. These compounds have been subjected for free radical reactions with DPPH radicals, superoxide radicals (O(2)(•-)), singlet oxygen ((1)O(2)) and peroxyl radicals (CCl(3)O(2)(•)) and the bimolecular rate constants were determined. The DPPH radical reactions were followed by stopped-flow spectrometer, (1)O(2) reactions by transient luminescence spectrometer, and CCl(3)O(2)(•) reactions using pulse radiolysis technique. The rate constants indicate that the presence of o-methoxy phenolic OH increases its reactivity with DPPH and CCl(3)O(2)(•), while for molecules lacking phenolic OH, this reaction is very sluggish. Reaction of O(2)(•-) and (1)O(2) with curcumin analogues takes place preferably at β-diketone moiety. The studies thus suggested that both phenolic OH and the β-diketone moiety of curcumin are involved in neutralizing the free radicals and their relative scavenging ability depends on the nature of the free radicals.

Dimethoxycurcumin (Dimc), a synthetic analogue of curcumin, that has been reported to exhibit better in vivo stability and anti-tumour activity, was investigated for its interaction with DNA, employing spectroscopic methods based on absorption, fluorescence, circular dichroism (CD), ethidium bromide (EtBr) competitive binding assay, 4'-6-diamidino-2-phenylindole (DAPI) displacement assay and fluorescence resonance energy transfer (FRET) assay. The mean binding constant for its interaction with calf thymus DNA (ct-DNA) was estimated to be 4.4±0.8 × 10(4) m(-1) . The studies using CD revealed that Dimc did not cause unwinding of the ct-DNA helix or induce major conformational changes. The EtBr and DAPI assays indicated that Dimc is not an intercalator but a minor groove binder. FRET assay also confirmed that Dimc interacts with DNA strands. Furthermore, viscosity measurements of ct-DNA solutions in the presence of Dimc supported these spectroscopic observations. Addition of Dimc to MCF-7 cells showed nuclear localization as visualized by confocal microscopy. In conclusion, the present studies addressed the mode of interaction of Dimc with biomolecules, which may have implications in developing Dimc as a DNA-targeted drug.

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Two extracts E1and E2 were prepared from the dried root of the plant Caesalpinia digyna by extracting with solvents of different polarity. The extracts were standardized with respect to a polyphenol, bergenin, by LC- MS analysis and they were subjected to free radical scavenging activity and in vitro radioprotection studies. Free radical reactions were carried out with superoxide, hydroxyl, and peroxyl radicals and DPPH. In vitro radioprotecting activity was studied by following their effect on gamma-radiation induced lipid peroxidation, protein carbonylation and DNA damage. The results indicated that E1 with higher free radical scavenging ability is also a more potent inhibitor of radiation induced damage to proteins, DNA and liposomes than E2. Comparing the results with those for bergenin indicated that bergenin alone is not responsible for the free radical scavenging ability and in vitro radioprotection. The studies also confirmed that the extracts enriched with bergenin are more effective than the isolated polyphenol, bergenin.

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