Reactions of reactive oxygen species (ROS) with curcumin analogues: Structure–activity relationship

Abstract

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.

Electron Paramagnetic Resonance Study of the Free Radical Scavenging Capacity of Curcumin and Its Demethoxy and Hydrogenated Derivatives

“…The methoxy substitution on phenyl ring did not significantly increase the reaction rate constant with superoxide anion radical. 16) Our findings supported the importance of the keto-enol moiety. However, the decrease scavenging activity of Dmc and Bdmc may imply the effect of the ortho-methoxyphenolic group.…”

“…This may be related primarily to the differences in the ability to donate hydrogen atoms from a phenolic vs. enolic group due the differences in their chemical structure. [7][8][9]15,16,24,25) The additional hydroxyl group in OHC and the hydrogen atom from the central methylenic group may also contribute to the hydrogen donating ability of these hydrogenated derivatives. 26) In addition, the results confirmed that loss of the orthomethoxyphenolic group in Bdmc caused a greater loss of hydrogen donating activity, whereas the molecule with an ortho-methoxyphenolic group and β-diketone moiety showed the comparable activity to trolox.…”

“…Singh et al 16) has demonstrated effective scavenging activity of curcumin and its analogues towards superoxide anion radicals, and single oxygen and peroxyl radicals and performed kinetic analyses of the radical reaction. These studies have provided informative data regarding the structure-activity relationship (SAR) of curcumin and its analogues.…”

The Effect of Curcumin Supplementation on Selected Markers of Delayed Onset Muscle Soreness (DOMS)

“…Oxidative stress induced by lipid peroxidation may lead to membrane permeability that would allow muscle constituents such as CK and aminotransferases to escape (30). The phenolic compound of curcumin acts as a scavenger of reactive oxygen species and a quencher of the lipid peroxidative side chain (31) prevented CK leakage and other related enzymes from cell membranes and consequently less increase in CK serum level. Previous studies have confirmed that supplements containing antioxidants are able to attenuate these enzymes (32,33).…”

Characterization of a novel curcumin analog P1 as potent inhibitor of the NF-κB signaling pathway with distinct mechanisms

“…Curcumin is the most able to suppress TNF-induced NF-κB activation, followed by DMC and BDMC. In contrast, when pro-oxidant activity was examined, BDMC was maximally active at inducing ROS, whereas curcumin and DMC had minimal activity, suggesting that these compounds elicit anti-tumor activity through different mechanisms [41] . Nevertheless, the piperidin-4-one curcumin analog EF-24 has been shown to induce apoptosis by upregulating cellular antioxidant responses [42] .…”