curcumin and diacetylcurcumin

Topics: alpha-Tocopherol; Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Butylated Hydroxytoluene; Cations, Divalent; Cell Line, Tumor; Cisplatin; Coordination Complexes; Copper; Crystallography, X-Ray; Curcumin; Epithelial Cells; Humans; Inhibitory Concentration 50; Ligands; Lipid Peroxidation; Magnesium; Male; Manganese; MCF-7 Cells; Mice; Models, Molecular; Toxicity Tests, Acute; Zinc

This study evaluated the effect of antimicrobial photodynamic therapy (aPDT) on

Topics: Anti-Bacterial Agents; Biofilms; Curcumin; Humans; Microbial Viability; Photochemotherapy; Photosensitizing Agents; Streptococcus mutans

The present study aims to evaluate the antiarthritic activity of diacetylcurcumin (DAC), a synthetic derivative where the free phenolic groups of curcumin are derivatized by acetylation, thereby conferring greater lipophilicity to the parent molecule and partially overcoming the limited systemic bioavailability of curcumin. Antiarthritic activity was evaluated on a Freund's complete adjuvant (FCA)-induced murine model of arthritis. Oral administration of DAC (60 and 120 mg/kg) resulted in a significant inhibition of inflammation in the acute and chronic phases, respectively, demonstrating an improved and sustained anti-inflammatory effect, comparable to that of curcumin (150 mg/kg) in the chronic stage at a lower dose. Phenylbutazone (80 mg/kg) was used as a reference drug. The pharmacological consequence of DAC or curcumin treatment is the prevention of secondary lesions commonly associated with this biological model.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Chromatography, High Pressure Liquid; Curcumin; Disease Models, Animal; Freund's Adjuvant; Magnetic Resonance Spectroscopy; Mice; Rats; Treatment Outcome

Staphylococcus aureus infections have contributed to the global healthcare burden, particularly with regard to hospital-acquired meticillin-resistant S. aureus (MRSA) infections.. This study describes the antibacterial activity of diacetylcurcumin (DAC) against meticillin-susceptible S. aureus/MRSA biofilm formation, survival, metabolic activity and structure; its ability to prevent bacterial adhesion to human cells; and toxicity in Galleria mellonella larvae.. DAC showed excellent antibacterial activity, with MIC ranging between 17.3 and 34.6 µmol l-1, and minimum bactericidal concentration ranging between 69 and 277 µmol l-1. It significantly reduced bacterial biofilm survival - by 22-63 % (at MIC, 10×MIC or 100×MIC) as compared to the 25-42 % reduction by vancomycin (P<0.0001) - and severely affected biofilm cell structures, leading to damaged architecture and the formation of amorphous cell clusters. Treatment with DAC (MIC/4) decreased bacterial adhesion to HaCaT keratinocytes from 1 to 5 h (P<0.0001). Finally, DAC demonstrated low toxicity in G. mellonella at its effective anti-biofilm concentrations.. These findings open new avenues for the study of this curcumin derivative as an excellent prototype with anti-MRSA activity.

Topics: Adhesins, Bacterial; Animals; Anti-Bacterial Agents; Biofilms; Curcumin; Humans; Keratinocytes; Larva; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Moths; Staphylococcal Infections; Staphylococcus aureus

It was reported that bovine α-lactalbumin (BLA) as an important whey protein can be utilized as valuable vehicle for metal ions. The goal of this study was to investigate the interaction of BLA with bisdemethoxycurcumin (BDMC), Diacetylcurcumin (DAC), and diacetylbisdemethoxycurcumin (DABC) as three bioactive compounds by fluorescence quenching measurements and docking studies. It was observed that these ligands come closer to tryptophan residues and quench their emission without any change in their micro region polarity. The Stern-Volmer equation which is the best model to provide information about the interaction between small bioactive molecules and proteins was used to obtain the binding constants and the binding stoichiometry. Information about the extent of resonance energy transfer and Förster's distance between donor and acceptor was estimated. Thermodynamic parameters confirmed that the final BDMC-BLA complex was stabilized by hydrogen bonds, whereas the final DABC-BLA and DAC-BLA complexes were stabilized by hydrophobic bonds which are in accordance with their chemical structures. Both the synchronous and docking studies verified that theTrp-26 which is the most exposed Tryptophan residue has the most contribution in the binding process. The Förster's distances between bound ligands and tryptophans were in agreement with the measured distances by docking studies. The obtained achievements confirmed that there are considerable binding interactions between these curcuminoids and BLA.

Topics: Amino Acid Motifs; Animals; Binding Sites; Cattle; Crystallography, X-Ray; Curcumin; Diarylheptanoids; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Kinetics; Lactalbumin; Molecular Docking Simulation; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Thermodynamics

Curcumin has a wide spectrum of biological and pharmacological activities including anti-inflammatory, antioxidant, antiproliferative, antimicrobial and anticancer activities. Complexation of curcumin with metals has gained attention in recent years for improvement of its stability. In this study, the effect of gallium curcumin and gallium diacetylcurcumin on the structure, function and oxidative stability of horseradish peroxidase (HRP) enzyme were evaluated by spectroscopic techniques. In addition to the enzymatic investigation, the cytotoxic effect of the complexes was assessed on bladder, MCF-7 breast cancer and LNCaP prostate carcinoma cell lines by MTT assay. Furthermore, antibacterial activity of the complexes against S. aureus and E. coli was explored by dilution test method. The results showed that the complexes improve activity of HRP and also increase its tolerance against the oxidative condition. After addition of the complexes, affinity of HRP for hydrogen peroxide substrate decreases, while the affinity increases for phenol substrate. Circular dichroism, intrinsic and synchronous fluorescence spectra showed that the enzyme structure around the catalytic heme group becomes less compact and also the distance between the heme group and tryptophan residues increases due to binding of the complexes to HRP. On the whole, it can be concluded that the change in the enzyme structure upon binding to the gallium curcumin and gallium diacetylcurcumin complexes results in an increase in the antioxidant efficiency and activity of the peroxidise enzyme. The result of anticancer and antibacterial activities suggested that the complexes exhibit the potential for cancer treatment, but they have no significant antibacterial activity.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Cell Line, Tumor; Circular Dichroism; Coordination Complexes; Curcumin; Enzyme Activation; Female; Gallium; Humans; Male; Molecular Structure; Oxidation-Reduction; Peroxidase; Spectrometry, Fluorescence

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Cell Line, Tumor; Coordination Complexes; Curcumin; Enzyme Activation; Enzyme Stability; Female; Gallium; Humans; Male; Molecular Structure; Oxidation-Reduction; Peroxidase

The interaction of diacetylcurcumin (DAC), as a novel synthetic derivative of curcumin, with bovine β-casein (an abundant milk protein that is highly amphiphilic and self assembles into stable micellar nanoparticles in aqueous solution) was investigated using fluorescence quenching experiments, Forster energy transfer measurements and molecular docking calculations. The fluorescence quenching measurements revealed the presence of a single binding site on β-casein for DAC with the binding constant value equals to (4.40±0.03)×10(4)M(-1). Forster energy transfer measurements suggested that the distance between bound DAC and Trp143 residue is higher than the respective critical distance, hence, the static quenching is more likely responsible for fluorescence quenching other than the mechanism of non-radiative energy transfer. Our results from molecular docking calculations indicated that binding of DAC to β-casein predominantly occurred through hydrophobic contacts in the hydrophobic core of protein. Additionally, in vitro investigation of the cytotoxicity of free DAC and DAC-β-casein complex in human breast cancer cell line MCF7 revealed the higher cytotoxic effect of DAC-β-casein complex.

Topics: Animals; Caseins; Cattle; Cell Death; Curcumin; Fluorescence Resonance Energy Transfer; Humans; Ligands; MCF-7 Cells; Micelles; Molecular Docking Simulation; Nanoparticles; Nephelometry and Turbidimetry; Protein Binding; Solutions; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet

Leishmania parasites are intracellular haemoflagellates that infect macrophages of the skin and viscera to produce diseases in their vertebrates hosts. Antileishmania therapy is based on pentavalent antimony compounds which toxicity of these agents and the persistence of side effects are severe. Curcumin was identified to be responsible for most of the biological effects of turmeric. Turmeric plant extracts (curcumin and other derivatives) have anti-inflammatory, anti-arthritic, antioxidant, anti-microbial, antileishmanial, hepato protective, anti-cancer, anti-ulcer and anti diabetic activity.. Stock solutions of curcumin, indium curcumin, diacetylcurcumin and Gallium curcumin were made up in DMSO. From the each stock solution serial dilutions were made with phosphate buffered saline and 100 µl of each prepared concentration was added to each well of 96-well micro plate. All tests were performed in triplicate. Negative control only received RPMI-1640 medium with a parasite density of 106 parasites /ml and the positive control contained varying concentrations of standard antileishmania compound, Amphotericine B. MTT solution was prepared as 5 mg/ml in RPMI-1640 and 20 µl of this concentration was added to each well. Antileishmania effects of test agents and control were evaluated by using the MTT assay.. Mean growth inhibition of triplicate for each concentration of test agents and control were measured. The IC50 values for curcumin, gallium curcumin [ga (CUR) 3], indium curcumin [in (CUR)3], Diacethyle Curcumin (DAC ) and Amphotericine B were 38 µg/ml, 32 µg/ml, 26 µg/ml, 52 µg/ml and 20 µg/ml respectively. Indium curcumin [in (CUR) 3] with IC50 values of 26 µg/ml was more effective than other three test agents against Leishmania. Mean growth inhibition of triplicate for Amphotericine B as control drug, was 20 µg/ml.. Indium curcumin and Gallium curcumin complex showed more antileishmanial activity than curcumin and diacetylcurcumin and could be suitable candidates for further investigations.

Topics: Curcuma; Curcumin; Dose-Response Relationship, Drug; Gallium; Indium; Inhibitory Concentration 50; Leishmania major; Parasitic Sensitivity Tests; Phytotherapy; Plants, Medicinal; Trypanocidal Agents

The binding of curcumin (CUR) and diacetylcurcumin (DAC) to bovine beta-lactoglobulin (BLG) genetic variant B was investigated by fluorescence and circular dichroism techniques. The binding parameters including number of substantive binding sites and the binding constants have been evaluated by fluorescence quenching method. The distance (r) between donor (BLG) and acceptor (CUR and DAC) was obtained according to the Förster's theory of non-radiative energy transfer. The far-UV circular dichroism spectra were used to investigate the possible changes in the secondary structure of BLG in the presence of CUR and DAC and showed that these two ligands change the alpha-helix and random coil contents of this protein to some extent. The visible circular dichroism spectra indicated that the optical activity during the ligand binding was observed due to the induced-protein chirality. All of the achieved results suggested the important role of the phenolic OH group of CUR in the binding process resulted in more affinity of CUR than DAC for binding to BLG.

Topics: Animals; Binding Sites; Cattle; Circular Dichroism; Curcumin; Fluorescence Resonance Energy Transfer; Lactoglobulins; Lipocalins; Protein Binding; Spectrometry, Fluorescence

The current study reports the binding of curcumin (CUR) as the main pharmacologically active ingredient of turmeric and diacetylcurcumin (DAC) as a bioactive derivative of curcumin to human serum albumin (HSA) and bovine serum albumin (BSA). The apparent binding constants and number of substantive binding sites have been evaluated by fluorescence quenching method. The distance (r) between donor (HSA and BSA) and acceptor (CUR and DAC) was obtained on the basis of the Förster's theory of non-radiative energy transfer. The minor changes on the far-UV circular dichroism spectra resulted in partial changes in the calculated secondary structure contents of HSA and BSA. The negligible alteration in the secondary structure of both albumin proteins indicated that ligand-induced conformational changes are localized to the binding site and do not involve considerable changes in protein folding. The visible CD spectra indicated that the optical activity observed during the ligand binding due to induced-protein chirality. All of the achieved results suggested the important role of the phenolic OH group of CUR in the binding process.

Topics: Animals; Cattle; Circular Dichroism; Curcumin; Humans; Serum Albumin; Serum Albumin, Bovine; Spectrometry, Fluorescence

Curcumin is a natural product with diverse pharmacological activities. Studies of curcumin and its structural derivatives have been a subject of growing interest as a result of their diverse biological activities. We report the interaction of diacetylcurcumin (DAC) with Ribonuclease A (RNase A). The binding constant of DAC with RNase A was found to be of the order of 10(4) M(-1). The intrinsic fluorescence of RNase A was quenched by DAC with a quenching constant of 2.2 x10(4) M(-1). The distance between the fluorophore of RNase A and DAC was found to be 2.6 nm, calculated from a Förster type fluorescence resonance energy transfer (FRET). Secondary structural changes of RNase A after binding were analyzed from circular dichroism and Fourier transform infrared studies. Protein-ligand docking studies were conducted to determine the residues involved in the interaction of RNase A with DAC and changes in the accessible surface of the interacting residues were calculated accordingly.

Topics: Binding Sites; Curcumin; Ligands; Ribonuclease, Pancreatic

The interaction of bovine serum albumin (BSA) with isoxazolcurcumin (IOC) and diacetylcurcumin (DAC) has been investigated. Binding constants obtained were found to be in the 10(5) M(-1) range. Minor conformational changes of BSA were observed from circular dichroism (CD) and Fourier transformed infrared (FT-IR) studies on binding. Based on Förster's theory of non-radiation energy transfer, the average binding distance, r between the donor (BSA) and acceptors IOC and DAC was found to be 3.79 and 4.27 nm respectively. Molecular docking of isoxazolcurcumin and diacetylcurcumin with bovine serum albumin indicated that they docked close to Trp 213, which is within the hydrophobic subdomain.

Topics: Animals; Binding Sites; Circular Dichroism; Curcumin; Energy Transfer; Hydrophobic and Hydrophilic Interactions; Protein Binding; Serum Albumin, Bovine; Spectroscopy, Fourier Transform Infrared

This study aimed to investigate the mechanism underlying the protective effects of manganese complexes of curcumin (Cp-Mn) and diacetylcurcumin (DiAc-Cp-Mn) on kainic acid (KA)-induced excitotoxicity in the rat hippocampus. Systemic injection of KA (10 mg/kg, i.p.) caused seizures and increased the expression of neurotoxic markers, immediate early genes [c-jun, cyclooxygenase 2 (COX-2), brain-derived neurotrophic factor (BDNF), and heat shock protein 70 (hsp70)] and a delayed response gene [inducible nitric oxide synthase (iNOS)], which were measured at 6 and 72 h after KA injection, respectively, in the hippocampus. Pretreatment with Cp-Mn (50 mg/kg, i.p.) and DiAc-Cp-Mn (50 mg/kg, i.p.) but not with curcumin (50 mg/kg, i.p.) delayed the onset of KA-induced seizure without affecting the seizure score. KA injection induced c-Fos immunoreactivity in DG, CA1, and CA3 hippocampal regions, the expression of which peaked at 6 h after injection. Cp-Mn and DiAc-Cp-Mn treatment significantly decreased c-Fos expression elicited by KA. Moreover, Cp-Mn and DiAc-Cp-Mn administration suppressed the KA-induced expression of c-jun, COX-2, BDNF, and iNOS mRNA, whereas curcumin attenuated only iNOS mRNA expression. No compounds tested had an effect on KA-induced hsp70 expression. It is therefore likely that in addition to radical scavenging and SOD-like activities, the suppression of potential neuronal injury marker expression by Cp-Mn and DiAc-Cp-Mn, contributes to the neuroprotective activities of these compounds, which are superior to those of curcumin, on KA-induced excitotoxicity in the hippocampus. These results suggest the beneficial effects of Cp-Mn, and DiAc-Cp-Mn on the treatment of excitotoxicity-induced neurodegenerative diseases.

Topics: Animals; Behavior, Animal; Brain-Derived Neurotrophic Factor; Cell Death; Curcumin; Cyclooxygenase 2; Excitatory Amino Acid Agonists; Hippocampus; HSP70 Heat-Shock Proteins; Immunohistochemistry; Kainic Acid; Male; Manganese; Neurons; Neurotoxicity Syndromes; Nitric Oxide Synthase Type II; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Seizures

Curcumin is a natural antioxidant isolated from the medicinal plant Curcuma longa Linn. We previously reported that manganese complexes of curcumin (Cp-Mn) and diacetylcurcumin (DiAc-Cp-Mn) exhibited potent superoxide dismutase (SOD)-like activity in an in vitro assay. Nitric oxide (NO) is a free radial playing a multifaceted role in the brain and its excessive production is known to induce neurotoxicity. Here, we examined the in vivo effect of Cp-Mn and DiAc-Cp-Mn on NO levels enhanced by kainic acid (KA) and L-arginine (L-Arg) in the hippocampi of awake rats using a microdialysis technique. Injection of KA (10 mg/kg, i.p.) and L-Arg (1000 mg/kg, i.p.) significantly increased the concentration of NO and Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.) significantly reversed the effects of KA and L-Arg without affecting the basal NO concentration. Following KA-induced seizures, severe neuronal cell damage was observed in the CA1 and CA3 subfields of hippocampal 3 days after KA administration. Pretreatment with Cp-Mn and DiAc-Cp-Mn (50 mg/kg, i.p.) significantly attenuated KA-induced neuronal cell death in both CA1 and CA3 regions of rat hippocampus compared with vehicle control, and Cp-Mn and DiAc-Cp-Mn showed more potent neuroprotective effect than their parent compounds, curcumin and diacetylcurcumin. These results suggest that Cp-Mn and DiAc-Cp-Mn protect against KA-induced neuronal cell death by suppression of KA-induced increase in NO levels probably by their NO scavenging activity and antioxidative activity. Cp-Mn and DiAc-Cp-Mn have an advantage to be neuroprotective agents in the treatment of acute brain pathologies associated with NO-induced neurotoxicity and oxidative stress-induced neuronal damage such as epilepsy, stroke and traumatic brain injury.

Topics: Animals; Apoptosis; Arginine; Curcumin; Excitatory Amino Acid Agonists; Hippocampus; Kainic Acid; Male; Manganese; Neurons; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Seizures

Curcumin manganese complex (CpCpx) and diacetylcurcumin manganese complex (AcylCpCpx) were determined as to their effect on the nitric oxide (NO) radical scavenging in vitro method using a sodium nitroprusside generating NO system compared with their parent compound and astaxanthin, an extreme antioxidant. All compounds effectively reduced the generation of NO radicals in a dose dependent manner. They exhibited strong NO radical scavenging activity with low IC(50) values. The IC(50) values of curcumin, diacetylcurcumin, CpCpx and AcylCpCpx obtained are 20.39+/-4.10 microM, 28.76+/-1.48 microM, 9.79+/-1.50 microM and 8.09+/-0.99 microM, respectively. CpCpx and AcylCpCpx show greater NO radical scavenging than their parent compounds, curcumin and acetylcurcumin, respectively. However, the IC(50) values of curcumin and related compounds were found to be less than astaxanthin, an extreme antioxidant, with the lower IC(50) value of 3.42+/-0.50 microM.

Topics: beta Carotene; Curcumin; Free Radical Scavengers; Manganese; Nitric Oxide; Nitroprusside; Quercetin; Structure-Activity Relationship; Xanthophylls