dimethoxycurcumin and bisdemethoxycurcumin

The curcumin-C3 (cur-C3) complex obtained from Curcuma longa rhizome is a combination of three curcuminoids, namely, curcumin, dimethoxycurcumin, and bisdemethoxycurcumin. Cur and curcuminoids have been extensively researched for their wide range of therapeutic properties against inflammatory diseases, diabetes, and cancer.. In spite of their extensive medicinal properties, cur and curcuminoids have poor solubility and bioavailability due to their hydrophobicity. This limitation can be overcome by complexing cur-C3 with natural cyclic oligosaccharides, such as Cyclodextrin (CD).. In this study, cur-C3 and CD (α, β) inclusion complexes (ICs) were prepared with different molar ratios and characterized by nuclear magnetic resonance, Fourier transform infrared spectroscopy, X-ray diffraction, and transmission electron microscopy.. The cur-C3 cyclodextrin ICs showed an increased entrapment efficiency of 97.8% and improved antioxidant activity compared to cur and can be used as an antioxidant to reduce cancer-related oxidative stress. Additionally, α- CD ICs of curcumin-C3 caused an increase in growth inhibition of Staphylococcus aureus.. Our findings suggest that both α- and β-CDs are suitable carriers for cur-C3 and can be used as an effective treatment for cancer-associated oxidative stress and as a preventive treatment for nosocomial infections and pneumonia.

Topics: alpha-Cyclodextrins; Anti-Bacterial Agents; Antioxidants; beta-Cyclodextrins; Biological Availability; Curcumin; Diarylheptanoids; Drug Compounding; Escherichia coli; Hydrophobic and Hydrophilic Interactions; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

The presence of β-amyloid (Aβ) containing plaques in the brain is a hallmark of Alzheimer's disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Early diagnosis is of great importance for optimal treatment and for monitoring disease progression in the brain. Highly specific and sensitive biomarkers are thus greatly needed to assess therapeutic efficacy, not only clinically, but also in terms of clearance of histopathological lesions and decelerated neurodegeneration. The objective of the present study was to give more insight into the binding of curcumin analogues, curcuminoids, to Aβ containing plaques in postmortem tissue from AD patients. In vitro autoradiography was utilized to explore affinity and displacement of the curcuminoids; curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) and dimethoxycurcumin (DIMC). We found that BDMC had the highest affinity for Aβ containing plaques in cortical AD brain tissue in comparison to other curcuminoids. Subsequently, [(3)H]BDMC showed significantly higher specific binding in cortical AD brain tissue compared to control subjects. These findings suggest that curcumin analogues, especially BDMC, may serve as a potential radioligands for Aβ plaque neuroimaging.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aminopyridines; Amyloid beta-Peptides; Autoradiography; Benzothiazoles; Curcumin; Diarylheptanoids; Female; Humans; Inhibitory Concentration 50; Male; Temporal Lobe

The B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) locus encodes a 37-kD protein that is a key regulatory component of the polycomb regulatory complex 1 (PRC1). When overexpressed in various cancer types, the BMI1 protein induces cell growth and promotes tumor growth in vitro and in vivo. Curcumin, a major phytochemical in turmeric (Curcuma longa), inhibits the proliferation and survival of many types of cancer cells, both in vitro and in vivo, and has been reported to reduce BMI1 expression in breast cancer cells. In this study, effects of curcumin and two analogs (bisdemethoxycurcumin and dimethoxycurcumin) on BMI1 expression were evaluated in DLD-1 colorectal cancer cells. Bisdemethoxycurcumin (BDMC) is naturally occurring in turmeric, whereas dimethoxycurcumin (DMC) is a synthetic analog of curcumin. All three compounds reduced cell survival, but only the natural compound downregulated BMI1 protein expression; curcumin significantly reduced BMI1 levels more than bisdemethoxycurcumin and dimethoxycurcumin. In addition, curcumin and BDMC inhibit survival of the DLD-1 colorectal cancer cells by inducing apoptosis, whereas DMC inhibits survival by a mechanism other than apoptosis.

Topics: Adult; Antineoplastic Agents; Apoptosis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Curcumin; Diarylheptanoids; Down-Regulation; Humans; Male; Polycomb Repressive Complex 1

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.

Topics: Biphenyl Compounds; Carbon Tetrachloride; Curcumin; Diarylheptanoids; Free Radical Scavengers; Free Radicals; Hydroxyl Radical; Peroxides; Picrates; Pulse Radiolysis; Reactive Oxygen Species; Singlet Oxygen; Spectrum Analysis; Structure-Activity Relationship; Superoxides

The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1:1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Trypanosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC(50) for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 microM, respectively). Among 43 curcuminoid analogs and 8 pairs of 1:1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in submicromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (40) was the most active compound, with an EC(50) value of 0.053+/-0.007 microM; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC(50) 0.12+/-0.01 microM). Using a previously characterized diminazene-resistant T. b. brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against T. b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC(50) values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16+/-3 and 37+/-6 microM, respectively) while the control drug, pentamidine, displayed an EC(50) of 16+/-2 microM. Among the active curcuminoid analogs, four compounds exhibited EC(50) values of less than 5 microM against Leishmania major promastigotes and four against L. mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T. b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T. b. brucei ranged from 3-fold to 15

Topics: Antimalarials; Cell Line; Curcumin; Diarylheptanoids; Humans; Inhibitory Concentration 50; Leishmania; Molecular Structure; Trypanocidal Agents; Trypanosoma