- Effects of Stable Degradation Products of Curcumin on Cancer Cell Proliferation and Inflammation
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Curcumin is among the most promising dietary compounds for cancer prevention. However, curcumin rapidly degrades in aqueous buffer at physiological pH, making it difficult to understand whether the effects of curcumin are from curcumin itself or its degradation products. Here we studied the antiproliferative and anti-inflammatory effects of curcumin degradation products, including its total degradation products (a mixture containing all stable degradation products of curcumin) and bicyclopentadione (a dominant stable degradation compound of curcumin). Curcumin potently modulated cell proliferation, progression of cell cycle, and apoptosis in MC38 colon cancer cells and inhibited lipopolysaccharide (LPS)-induced inflammatory responses and NF-κB signaling in RAW 264.7 macrophage cells. In contrast, neither the total degradation products of curcumin nor bicyclopentadione had such effects. For example, after 24 h of treatment in MC38 colon cancer cells, 5 μg/mL curcumin inhibited 39.2 ± 1.8% of cell proliferation, whereas its degradation products were inactive. Together, these results suggest that the stable chemical degradation products of curcumin are not likely to play a major role in mediating the biological activities of curcumin.
- Sanidad, Katherine Z.,Zhu, Julia,Wang, Weicang,Du, Zheyuan,Zhang, Guodong
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- Novel flourescent spiroborate esters: potential therapeutic agents in in vitro cancer models
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The current treatment system in cancer therapy, which includes chemotherapy/radiotherapy is expensive and often deleterious to surrounding healthy tissue. Presently, several medicinal plants and their constituents are in use to manage the development and progression of these diseases.They have been found effective, safe, and less expensive. In the present study, we are proposing the utility of a new class of curcumin derivative, Rubrocurcumin, the spiroborate ester of curcumin with boric acid and oxalic acid (1:1:1), which have enhanced biostability for therapeutic applications. In vitro cytocompatibility of this drug complex was analysed using MTT assay, neutral red assay, lactate dehydrogenase assay in 3T3L1 adipocytes. Anti tumour activity of this drug complex on MCF7 and A431 human cancer cell line was studied by morphological analysis using phase contrast microscopy, Hoechst staining and cell cycle analysis by FACS. To explore the chemotherapeutic effect, the cytotoxic effect of this compound was also carried out. Rubrocurcumin is more biostable than natural curcumin in physiological medium. Our results prove that this curcumin derivative drug complex possess more efficacy and anti-cancer activity compared with curcumin. The findings out of this study suggests this novel compound as potential candidate for site targeted drug delivery.
- Anjana,Joseph, Josna,John, Jeena,Balachandran,Kumar, T. R. Santhosh,Abraham, Annie
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- Stable isotope labeling strategy for curcumin metabolite study in human liver microsomes by liquid chromatography-tandem mass spectrometry
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The identification of drug metabolites is very important in drug development. Nowadays, the most widely used methods are isotopes and mass spectrometry. However, the commercial isotopic labeled reagents are usually very expensive, and the rapid and convenient identification of metabolites is still difficult. In this paper, an 18O isotope labeling strategy was developed and the isotopes were used as a tool to identify drug metabolites using mass spectrometry. Curcumin was selected as a model drug to evaluate the established method, and the 18O labeled curcumin was successfully synthesized. The non-labeled and 18O labeled curcumin were simultaneously metabolized in human liver microsomes (HLMs) and analyzed by liquid chromatography/mass spectrometry (LC-MS). The two groups of chromatograms obtained from metabolic reaction mixture with and without cofactors were compared and analyzed using Metabolynx software (Waters Corp.; Milford, MA, USA). The mass spectra of the newly appearing chromatographic peaks in the experimental sample were further analyzed to find the metabolite candidates. Their chemical structures were confirmed by tandem mass spectrometry. Three metabolites, including two reduction products and a glucuronide conjugate, were successfully detected under their specific HLMs metabolic conditions, which were in accordance with the literature reported results. The results demonstrated that the developed isotope labeling method, together with post-acquisition data processing using Metabolynx software, could be used for fast identification of new drug metabolites.
- Gao, Dan,Chen, Xiaowu,Yang, Xiaomei,Wu, Qin,Jin, Feng,Wen, Hongliang,Jiang, Yuyang,Liu, Hongxia
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- Synthesis, characterization and antimicrobial studies of Cd(II), Hg(II), Pb(II), Sn(II) and Ca(II) complexes of curcumin
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Cd(II), Hg(II), Pb(II), Sn(II) and Ca(II) complexes of curcumin have been prepared and characterized on the basis of their analytical, spectral and conductance data. In all the complexes, curcumin behaved as a monobasic bidentate ligand in which the intramolecularly hydrogen-bonded enolic proton is replaced by the metal ion. The antifungal (with Aspergillus niger, Aspergillus flavus, Aspergillus heteromorphus and Penicillium verruculosum ) and antibacterial (with Bacillus cereus ) studies reveal that metal complexation considerably increased the activity of curcumin, and among the complexes, Sn(II) complex exhibited maximum activity except for A. flavus where Hg(II) complex is more active.
- Pallikkavil, Radhika,Ummathur, Muhammed Basheer,Sreedharan, Sajith,Krishnankutty, Krishnannair
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- Phenol radical cations and phenoxyl radicals in electron transfer from the natural phenols sesamol, curcumin and trolox to the parent radical cations of 1-chlorobutane
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The free electron transfer from sesamol, curcumin and trolox to solvent (1-chlorobutane) radical cations was studied. The solutes (ArOH) react with BuCl.+ at diffusion-controlled rates (～1010dm 3mol-1s-1/s
- Joshi,Naumov,Kapoor,Mukherjee,Hermann,Brede
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- Platinum(II) Complexes of Curcumin Showing Photocytotoxicity in Visible Light
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Three platinum(II) complexes of curcumin, [Pt(NH3)2(cur)](NO3) (1), [Pt(en)(cur)](NO3) (2) and [Pt(dach)(cur)](NO3) (3), where Hcur is curcumin, en is ethylenediamine and dach is 1R,2R-(–)-1,2-diamino
- Mitra, Koushambi,Gautam, Srishti,Kondaiah, Paturu,Chakravarty, Akhil R.
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- Asymmetric 1,5-diarylpenta-1,4-dien-3-ones: Antiproliferative activity in prostate epithelial cell models and pharmacokinetic studies
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To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones (25–58) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58, with IC50 values in the range of 0.03–0.12 μM, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G0/G1 phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone.
- Zhang, Xiaojie,Guo, Shanchun,Chen, Chengsheng,Perez, German Ruiz,Zhang, Changde,Patanapongpibul, Manee,Subrahmanyam, Nithya,Wang, Rubing,Keith, Joshua,Chen, Guanglin,Dong, Yan,Zhang, Qiang,Zhong, Qiu,Zheng, Shilong,Wang, Guangdi,Chen, Qiao-Hong
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- Effects of different carboxylic ester spacers on chemical stability, release characteristics, and anticancer activity of mono-PEGylated curcumin conjugates
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We investigated the effects of different carboxylic ester spacers of mono-PEGylated curcumin conjugates on chemical stability, release characteristics, and anticancer activity. Three novel conjugates were synthesized with succinic acid, glutaric acid, and methylcarboxylic acid as the respective spacers between curcumin and monomethoxy polyethylene glycol of molecular weight 2000 (mPEG2000): mPEG2000-succinyl-curcumin (PSC), mPEG2000-glutaryl-curcumin (PGC), and mPEG2000-methylcarboxyl-curcumin (PMC), respectively. Hydrolysis of all conjugates in buffer and human plasma followed pseudo first-order kinetics. In phosphate buffer, the overall degradation rate constant and half-life values indicated an order of stability of PGC > PSC > PMC > curcumin. In human plasma, more than 90% of curcumin was released from the esters after incubation for 0.25, 1.5, and 2 h, respectively. All conjugates exhibited cytotoxicity against four human cancer cell lines: Caco-2 (colon), KB (oral cavity), MCF7 (breast), and NCI-H187 (lung) with half maximal inhibitory concentration (IC50) values in the range of 1-6 μM, similar to that observed for curcumin itself. Our results suggest that mono-PEGylation of curcumin produces prodrugs that are stable in buffer at physiological pH, release curcumin readily in human plasma, and show anticancer activity.
- Wichitnithad, Wisut,Nimmannit, Ubonthip,Callery, Patrick S.,Rojsitthisak, Pornchai
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- How curcumin works preferentially with water soluble antioxidants
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In this study we investigated physicochemical characteristics of the curcumin radical by pulse radiolysis and laser flash photolysis. Two methylated curcumin derivatives, methylcurcumin and trimethyl-curcumin, were synthesized to explore the role of phenol hydroxy and β-diketone moieties in the free radical chemistry of curcumin. Our results show that the initially generated β-oxo-alkyl transforms rapidly, probably via an intramolecular H-atom shift, into the phenoxyl-type curcumin radical. This phenoxyl does not react with oxygen, k 5 M-1 s-1, and can be repaired by any water-soluble antioxidant with appropriate redox potential, E6 6 M-1 s-1. A molecular mechanism of cancer chemoprevention by curcumin is proposed, with special emphasis on the synergism with water-soluble antioxidants.
- Jovanovic,Boone,Steenken,Trinoga,Kaskey
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- Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites
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The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had
- Ali, Wajid,Anjana, S. S.,Bhattacharya, Trisha,Chandrashekar, Hediyala B.,Goswami, Nupur,Guin, Srimanta,Maiti, Debabrata,Panda, Sanjib,Prakash, Gaurav,Saha, Argha,Sasmal, Sheuli,Sinha, Soumya Kumar
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supporting information
p. 1929 - 1940
(2022/02/01)
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- Design and synthesis of new curcuminoid compounds and their derivatives as antioxidant agents
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A series of new curcumin analogues and their derivatives were synthesized by reacting curcumin analogues with various substituted hydrazine compounds to afford new pyrazol derivatives. The preparation of ether and ester derivatives was also carried out. All synthesized compounds were characterized using FT-IR, 1HNMR, 13CNMR, and MS-ESI. The evaluations of these compounds have shown a good inhibition activity as antioxidant agents against the stable radical of diphenylpicrylhydrazyl (DPPH). Findings from this work demonstrated a high inhibition activity in compounds substituted with hydroxyl phenol groups in comparison with compounds with other groups.
- Abood, Rehab G.,Alsalim, Tahseen A.,Abood, Einas A.
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p. 2173 - 2183
(2021/04/22)
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- Principal component analysis based solvent map for optimisation of rate and yield of curcumin synthesis
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Curcumin, a diarylheptanoid normally isolated from Curcuma longa with multiple bioactivities, was synthesized from vanillin and pentane-1,4-dione as initial substrates, n-butylamine as a catalyst, boron oxide as a protecting agent, and tri-n-butyl borate as a water scavenger. The solvents play crucial roles in the reaction rate and the yield of curcumin synthesis. Applying principal component analysis (PCA) method on 89 molecular descriptors calculated for a set of 272 organic solvents, a two-dimensional solvent map was established. Two first principal components, which were found to characterize polarity and polarizability of solvents, accounted for 60% of the data variation and were used as the ordinates of the solvent map. Five solvents, including nhexane, N,N-dimethylacetamide, n-butyl acetate, chloroform and isopropanol, were selected from different areas of the solvent map to investigate the solvent effects on the rate and the yield of curcumin synthesis. The experimental results revealed that the highest formation rate and yield of curcumin were obtained in N,N-dimethylacetamide. The results offered direction for further explorations of the solvent map, in which N,N-dimethylacetamide should be used as a reference to find the optimum solvent for the synthetic procedure of curcumin.
- Nguyena, Vinh Tien,Hoanga, Hao Minh
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p. 693 - 701
(2021/02/09)
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- Extraction of curcumin from turmeric powder through complexation
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The complexation behavior of curcumin with boron and oxalic acid to form rubrocurcumin is utilized for the extraction of curcumin from turmeric powder. The complex formation reaction has been hastened by the addition of a phase transfer catalyst. To recover curcumin from the complex, the decomposition of the rubrocurcumin is studied. It was found that ammonia solution is a better reagent for the recovery of curcumin from its boron complex. The complexation of curcumin and its recovery by decomposition do not adversely affect curcumin, as ascertained by spectroscopic methods. This new approach for extraction of curcumin affords its isolation in an appreciable yield and in lesser time.
- Rajasekharan, Kallikat Narayanan,Thomas, Sherin Geevarghese
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p. 695 - 699
(2021/07/10)
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- Curcumin derivatives as photosensitizers in photodynamic therapy: Photophysical properties and: In vitro studies with prostate cancer cells
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Photodynamic therapy (PDT) is a minimally invasive approach to treat various forms of cancer, based on the ability of certain non-toxic molecules (photosensitizers) to generate reactive oxygen species (ROS) after excitation by light of a certain wavelength and eventually induce strong phototoxic reactions against malignant cells and other pathogens. Curcumin is one of the most extensively investigated phytochemicals with a wide range of therapeutic properties and has been shown to induce strong photocytotoxic effects in micromolar concentrations against a variety of cancer cell lines. Curcumin (1) is comparatively evaluated with the naturally occurring bisdemethoxy Curcumin (2), which lacks the two methoxy groups, as well as two newly synthesized curcuminoids, the cinnamaldehyde derivative (3) and the dimethylamino one (4), designed to increase the absorption maximum and hence the tissue penetration. The synthetic curcuminoids were successfully synthesized in sufficient amounts and their photophysical properties such as absorption, fluorescence, photobleaching and free radical generation were investigated. Compound 4 exhibited a significant increase in peak absorption (497 nm) and strong fluorescent emission signals were recorded for all curcuminoids. Photobleaching of 4 was comparable to 1 whereas 2 and 3 showed more extended photobleaching but much higher ROS production in very short irradiation times. Compounds 2 and 4 exhibited specific intracellular localization. After dark and light cytotoxicity experiments against LNCaP prostate cancer cell line for all curcuminoids, concentration of 3 μM and irradiance of 6 mW cm-2 were selected for the PDT application which resulted in remarkable results with very short LD50. Curcuminoids 2 and 4 exhibited a significant dose-dependent PDT effect. The biphasic dose-response photodynamic effect observed for 1 and 3 may provide a strategy against prolonged and sustained photosensitivity.
- Kazantzis,Koutsonikoli,Mavroidi,Zachariadis,Alexiou,Pelecanou,Politopoulos,Alexandratou,Sagnou
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p. 193 - 206
(2020/03/03)
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- Method for artificially synthesizing curcumin and derivatives thereof
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The invention provides a method for artificially synthesizing curcumin and derivatives thereof. The method comprises the following steps: reacting acetylacetone with boron oxide under a weakly acidiccondition to generate a complex, protecting methylene groups between two ketocarbonyl groups, adding a catalyst, reacting the complex with vanillin (benzaldehyde derivative) to obtain a curcumin derivative intermediate (I), and hydrolyzing the intermediate to obtain the curcumin derivative. The selectivity of the reaction is far higher than that of a preparation reaction in an alkaline system, andis macroscopically and specifically embodied in the yield of curcumin and derivatives thereof: in the existing two-pot reaction, the yield of curcumin in the whole process is about 60%; the yield ofthe preparation method can reach 80-90%. Therefore, the method provided by the invention reduces the waste of raw materials and the generation of byproducts; and complete hydrolysis can be realized only at normal temperature, insoluble substances included in the product are almost zero, and the obtained product is pure.
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Paragraph 0021-0027; 0050-0052
(2020/05/30)
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- ONE-STEP, FAST, 18F-19F ISOTOPIC EXCHANGE RADIOLABELING OF DIFLUORO-DIOXABORININS AND USE OF SUCH COMPOUNDS IN TREATMENT
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A compound according to Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, wherein X1 and X2 are each independently 18F or 19F; R1 and R2 are each independently alkyl, amine, perfluoroalkyl, alkenyl, alkynyl, aryl, or aralkenyl; and R3 is H, halo, alkyl, alkyl ester, alkenyl, alkynyl, aryl, or aralkenyl; or wherein: R1 and R3 or R2 and R3 join to form a 6-membered cycloalkyl or heterocyclyl; or R1 and R3, R2 and R3, or R1, R2, and R3 join to form a substituted or unsubstituted polycyclic ring, wherein the polycyclic ring comprises fused cycloalkyl, heterocycloalkyl, aryl, or heteroaryl rings.
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Paragraph 0019; 0206-0207
(2019/12/15)
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- Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
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Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.
- Deck, Lorraine M.,Hunsaker, Lucy A.,Vander Jagt, Thomas A.,Whalen, Lisa J.,Royer, Robert E.,Vander Jagt, David L.
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supporting information
p. 854 - 865
(2017/12/13)
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- Preparation method of curcumin
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The invention provides a preparation method of curcumin. According to the preparation method, the problems of high cost and heavy pollution of a traditional technique are solved. The preparation method is characterized in that vanillin and acetylacetone are used as raw materials and undergo Claisen ester condensation reaction under the catalytic action of tetrahydropyrrole and glacial acetic acid;a mode of slowly dropwise adding the acetylacetone is adopted in the reaction process so as to reduce side reaction; a large amount of expensive borate and boronic acid anhydride are not used any longer; after the reaction ends, a proper amount of solvent is recovered according to the conditions; an ammonium chloride saturated solution is added for carrying out quenching reaction, and a solid isseparated out by cooling; the curcumin can be obtained through simple filtering operation without post treatment procedures such as extraction, while the weakly acidic ammonium chloride saturated solution is adopted to replace strong acid in the traditional technique, so that safety and environmental protection are realized.
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Paragraph 0034; 0035; 0037; 0039; 0041; 0043; 0045
(2018/06/26)
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- Synthesis, characterization and ROS-mediated antitumor effects of palladium(II) complexes of curcuminoids
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Based on the synthesis of curcumin and its derivatives from aromatic aldehydes, a novel series of palladium(II) complexes with curcumin (or its derivatives) and 2,2′-bipyridine have been synthesized through a directed self-assembly approach that involves spontaneous deprotonation of the curcuminoid ligands in H2O/acetone solution. These complexes have been characterized by 1H (13C) NMR, HRMS and elemental analysis. Crystal structure of 3h has been determined by X-ray diffraction analysis. Their cytotoxicity was tested by MTT. The preliminary results showed that complexes 3d, 3f, 3h have significant inhibition on proliferation of three carcinoma cells such as MCF-7, HeLa and A549 cells, which were more active than cisplatin. Further mechanistic studies indicated that the tested complex 3h arrested the cell cycle in the S phase and can disrupted mitochondrial membrane potential and induced tumor cell apoptosis through reactive oxygen species (ROS)-dependent pathway.
- Li, Yanci,Gu, Zhenyu,Zhang, Can,Li, Shenghui,Zhang, Liang,Zhou, Guoqiang,Wang, Shuxiang,Zhang, Jinchao
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p. 662 - 671
(2018/01/01)
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- Structure-Activity Relationship of Curcumin: Role of the Methoxy Group in Anti-inflammatory and Anticolitis Effects of Curcumin
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Curcumin, a dietary compound from turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease. Most previous studies have focused on the structure-activity relationship of the thiol-reactive α,β-unsaturated carbonyl groups of curcumin, so little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogues with different substitution groups (R = H-, Br-, Cl-, F-, NO2-, CH3-, and OH-) to replace the methoxy group and evaluated their biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 μM) suppressed 74.91 ± 0.88, 77.75 ± 0.89, and 71.75 ± 0.90% of LPS-induced NO production, respectively (P 2, were inactive (P > 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse model, the Cur-Br analogue also showed a beneficial effect the same as curcumin (P 2 analogue had no effect in the animal model (P > 0.05). Together, the analogues have dramatically different effects on inflammation, supporting that the substitution group on the methoxy position plays an important role in the anti-inflammatory effects of curcumin. The methoxy group is a potential structural candidate for modification to design curcumin-based drugs for inflammatory diseases.
- Yang, Haixia,Du, Zheyuan,Wang, Weicang,Song, Mingyue,Sanidad, Katherine,Sukamtoh, Elvira,Zheng, Jennifer,Tian, Li,Xiao, Hang,Liu, Zhenhua,Zhang, Guodong
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p. 4509 - 4515
(2017/06/13)
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- METHODS AND FORMULATIONS FOR INCREASING CHEMICAL STABILITY AND BIOLOGICAL ACTIVITY OF PHENOLIC COMPOUNDS
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The present teachings show that co-addition of a series of redox active antioxidants with diverse chemical structures dramatically increases the chemical stability of dietary phenolic compounds, enhanced their biological activities in cells, and boosted the circulating concentrations of these compounds in animal models.
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Paragraph 0039
(2017/04/04)
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- Curcumin-amino acid conjugate and application
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The invention discloses curcumin-amino acid conjugate and application.The curcumin-amino acid conjugate has the following structure (please see the structure in the description).Experiments show that the curcumin-amino acid conjugate can obviously reduce release of mouse mononuclear macrophage RAW264.7 inflammation model NO induced by lipopolysaccharide, and the curcumin-amino acid conjugate shows an excellent inflammation resisting effect, has the advantages of being simple in preparation method, low in production cost, high in inflammation resisting activity, low in toxicity, easy to dissolve in water and high in bioavailability, and has great potential value in the aspect of anti-inflammatory drug development.
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Paragraph 0068; 0069
(2017/02/24)
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- The effectiveness of natural diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, ultrastructural alterations and molecular modeling studies
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Curcumin (CUR) is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC50 10.13 μM on epimastigotes). Demethoxycurcumin (DMC) was equipotent to CUR (IC50 11.07 μM), but bisdemethoxycurcumin (BDMC) was less active (IC50 45.33 μM) and cyclocurcumin (CC) was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel's mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of T. cruzi in a homology model and the results obtained showed that the observed interactions are in accordance with the IC50 values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations.
- Sueth-Santiago, Vitor,De Moraes, Jullianede B. B.,Alves, Eliomara Sousa Sobral,Vannier-Santos, Marcos Andre,Freire-De-lima, Celio G.,Castro, Rosane N.,Mendes-Silva, Gustavo Peron,De Nigris Del Cistia, Catarina,Magalh?es, Luma Godoy,Andricopulo, Adriano Defini,Santánna, Carlos Mauricio R.,Decote-Ricardo, Debora,Edilsonfreiredelima, Marco
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- Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson’s Disease
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Curcumin (CUR), a dietary polyphenol has diverse pharmacologic effects, but is limited by poor bioavailability. This is probably due to decreased solubility, cellular uptake and stability. In order to enhance its solubility and bioavailability, we synthesized the CUR bioconjugate curcumin monoglucoside (CMG) and tested its bioavailability, neuroprotective and anti-apoptotic propensity against rotenone (ROT) induced toxicity in N27 dopaminergic neuronal cells and Drosophila models. Our results elucidate that CMG showed improved bioavailability than CUR in N27 cells. Pre-treatment with CMG protected against ROT neurotoxicity and exerted antioxidant effects by replenishing cellular glutathione levels and significantly decreasing reactive species. CMG pre-treatment also restored mitochondrial complex I and IV activities inhibited by ROT. ROT-induced nuclear damage was also restored by CMG as confirmed by comet assay. CMG induced anti-apoptotic effects was substantiated by decreased phosporylation of JNK3 and c-jun, which in turn decreased the cleavage of pro-caspase 3. Q-PCR analysis of redox genes showed up-regulation of NOS2 and down-regulation of NQO1 upon ROT exposure and this was attenuated by CMG pre-treatment. Studies in the Drosophila ROT model revealed that, CMG administration showed better survival rate and locomotor activity, improved antioxidant activity and dopamine content than ROT treated group and was comparable with the CUR group. Based on these data, we surmise that CMG has improved bioavailability and offered neuroprotection comparable with CUR, against ROT-induced toxicity both in dopaminergic neuronal cell line and Drosophila models, with therapeutic implications for PD.
- Pandareesh,Shrivash,Naveen Kumar,Misra,Srinivas Bharath
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p. 3113 - 3128
(2016/11/11)
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- Identification of a new curcumin synthase from ginger and construction of a curcuminoid-producing unnatural fusion protein diketide-CoA synthase::curcumin synthase
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The biosynthesis and metabolic engineering of curcuminoids received considerable attention for their important pharmaceutical properties. In the present study, a new curcumin synthase (ZoCURS) was identified from ginger (Zingiber officinale). Notably, ZoCURS efficiently accepts 3-(4-hydroxyphenyl)propionyl-CoA to produce tetrahydrobisdemethoxycurcumin, which would be meaningful to further understand the biosynthesis of curcuminoids in ginger. In addition, a curcuminoid-producing unnatural fusion protein diketide-CoA synthase::curcumin synthase (DCS::CURS) was constructed. Comparing to ZoCURS, DCS::CURS indicated similar substrate specificities and catalytic potentials to catalyze the formation of various curcuminoids, however, the yield of curcuminoids produced by DCS::CURS was obviously increased, which would be useful for metabolic engineering of pharmaceutically important curcuminoid analogs, particularly including asymmetric dihydrocurcuminoids such as 3-(4-hydroxyphenyl)propionyl-feruloylmethane, 3-(4-hydroxyphenyl)propionyl-p-coumaroylmethane, and 3-(4-hydroxyphenyl)propionyl-cinnamoylmethane.
- Zhang, Le,Gao, Bowen,Wang, Xiaohui,Zhang, Zhongxiu,Liu, Xiao,Wang, Juan,Mo, Ting,Liu, Yuyu,Shi, Shepo,Tu, Pengfei
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p. 12519 - 12524
(2016/02/12)
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- COMPOUNDS FOR PREVENTING, REDUCING AND/OR ALLEVIATING ITCHY SKIN CONDITION(S)
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The present invention primarily relates to the use of one or more specific compounds and/or one or more respective salt(s) thereof for preventing, reducing or alleviating itchy skin condition(s), and/or as PAR-2 antagonist. Furthermore, the present invention relates to compositions (products or, respectively, formulations), in particular for topical administration, preferably cosmetic or pharmaceutical compositions, in particular for preventing, reducing or alleviating one or more itchy skin conditions and/or for providing a PAR-2 antagonistic effect, comprising or consisting of an effect amount of such compound(s) and/or salt(s) and one or more cosmetically and/or pharmaceutically acceptable carriers.
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Paragraph 0230; 0231; 0234; 0235
(2016/02/10)
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- Mechanochemical Synthesis and Antioxidant Activity of Curcumin-Templated Azoles
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A solvent-free, mechanochemical method for the synthesis of curcumin (1) derived 3,5-bis(styryl)pyrazoles and 3,5-bis(styryl)isoxazole (2a-g) at room temperature, with very short reaction time, is reported. Such earlier structural modifications of curcumin, at its β-diketone unit by transforming it into an isosteric pyrazole or isoxazole unit, required prolonged heating. The evaluation of the antioxidant activity of these compounds, based on DPPH, FRAP, and β-carotene bleaching assays, showed that several of these azoles are better antioxidants than curcumin, with the isoxazole derivative 2g being overall the best. Typically, the inhibition of 2,2-diphenyl-1-picrylhydrazyl (10-2 mmol), expressed as EC50 values, by curcumin (1), 3,5-bis(4-hydroxy-3-methoxystyryl)pyrazole (2a), and 3,5-bis(4-hydroxy-3-methoxystyryl)isoxazole (2g) are 40 ± 0.06, 14 ± 0.18, and 8 ± 0.11 μmol, respectively. Moreover, the reported method is useful in accessing 3,5-bis(4-hydroxy-3-methoxystyryl)-1-phenylpyrazole (2b), which is important in studies related to neuroprotection and Alzheimer's disease, and 2a and 2g, which are inhibitors of protein kinases involved in neuronal excitotoxicity.
- Sherin, Daisy R.,Rajasekharan, Kallikat N.
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p. 908 - 914
(2015/12/24)
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- METHOD FOR THE SYNTHESIS OF CURCUMIN
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The invention relates to a method for producing curcumin, characterized in that the boron-curcumin complex formed after condensation is isolated by filtration. The invention also relates to monohydrate curcumin and to methods for converting monohydrate cu
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Paragraph 0037; 0038
(2015/04/15)
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- Synthesis and biological evaluation of novel curcuminoid derivatives
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Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a-h, 15a-h and 19a-d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 μ M /mL against selected medically important Gram-positive cocci (S aureus and S viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 μ M.
- Cao, Ya-Kun,Li, Hui-Jing,Song, Zhi-Fang,Li, Yang,Huai, Qi-Yong
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p. 16349 - 16372
(2015/01/08)
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- Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents
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To improve the potential of curcumin to treat advanced hormone-refractory prostate cancer, three series (A-C) of heteroaromatic analogs (thirty two compounds) with different monoketone linkers have been synthesized and evaluated for cytotoxicity against two human androgen-independent prostate cancer cell lines (PC-3 and DU-145). Among them, thirty analogs are more potent than curcumin against PC-3 cells, and twenty one analogs are more cytotoxic towards DU-145 cells relative to curcumin. The most potent compounds (44, 45, 51, and 52) also showed impressive cytotoxicity against three other metastatic cancer cell lines (MDA-MB-231, HeLa, and A549), with IC50 values ranging from 50 nM to 390 nM. All four most potent analogs exhibited no apparent cytotoxicity towards the MCF-10A normal mammary epithelial cells. Taken together, selective enhancement of cell death in prostate cancer cell lines and other aggressive cancer cell lines suggests that nitrogen-containing heteroaromatic rings are promising bioisosteres of the substituted phenyl ring in curcumin. Published by Elsevier Masson SAS.
- Samaan, Nawras,Zhong, Qiu,Fernandez, Jayjoel,Chen, Guanglin,Hussain, Ali M.,Zheng, Shilong,Wang, Guangdi,Chen, Qiao-Hong
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p. 123 - 131
(2014/03/21)
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- Synthesis and evaluation of curcumin derivatives toward an inhibitor of beta-site amyloid precursor protein cleaving enzyme 1
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To research a new non-peptidyl inhibitor of beta-site amyloid precursor protein cleaving enzyme 1, we focused on the curcumin framework, two phenolic groups combined with an sp2 carbon spacer for low-molecular and high lipophilicity. The structure-activity relationship study of curcumin derivatives is described. Our results indicate that phenolic hydroxy groups and an alkenyl spacer are important structural factors for the inhibition of beta-site amyloid precursor protein cleaving enzyme 1 and, furthermore, non-competitive inhibition of enzyme activity is anticipated from an inhibitory kinetics experiment and docking simulation.
- Konno, Hiroyuki,Endo, Hitoshi,Ise, Satomi,Miyazaki, Keiki,Aoki, Hideo,Sanjoh, Akira,Kobayashi, Kazuya,Hattori, Yasunao,Akaji, Kenichi
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supporting information
p. 685 - 690
(2014/01/23)
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- NOVEL MODIFIED CURCUMINS AND THEIR USES
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This invention provides a compound having the structure (I) wherein α, β, A, B, and R1-R4 are defined herein. This invention also provides pharmaceutical compositions comprising the above compounds, a method of accelerating the healing of a wound, a method of inhibiting the activity and/or levels of a matrix metalloproteinase (MMP), a method of inhibiting the production of a cytokine in a population of cells, a method of inhibiting the production of a growth factor in a population of cells, and a method of inhibiting NFK-B activation in a population of cells.
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Page/Page column 50; 51
(2013/05/09)
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- Synthesis of thiophene and NO-curcuminoids for antiinflammatory and anti-cancer activities
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In search of better NSAIDs four novel nitric oxide donating derivatives of curcumin (compounds 9a-d), and four thiophene curcuminoids (compounds 10a-c, 11) have been synthesised. The cytotoxic effects of these compounds along with the lead compound curcumin (7) and their effect on the production of the reactive oxygen species nitric oxide and pro-inflammatory cytokines IL-1β, TNF-α and chemokine CXCL-8 were evaluated using human monocytic THP-1 and colon adenocarcinoma CACO-2 cell lines. All of the nitric oxide donating curcuminoids 9a-d and the thiophene curcuminoids 10a-c and 11 were non-cytotoxic to THP-1 cells over a concentration range of 10-100 μM and compared with curcumin compounds 10b and 10c, were more toxic. In CACO-2 cells, 10b and 11 appeared to be non-toxic at 10 to 50 μM, whereas 10a and 10c were non-cytotoxic at 10 μM only. These results clearly indicate that the introduction of a nitroxybutyl moiety to curcumin and replacement of phenyl rings with thiophene units reduces the cytotoxic effect of the parent curcumin, whereas a methyl substituted thiophene increases the cytotoxic effects. In THP-1 cells, drugs 10a and 11 significantly decreased IL-1-β production at their non-cytotoxic concentrations, whereas, they did not decrease TNF-α production in CACO-2 cells. Compound 11 showed a significant decrease in CXCL-8 production.
- Ahmed, Mahera M.,Khan, M. Akram,Rainsford, Kim Drummond
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p. 1483 - 1501
(2013/04/23)
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- BF3·OEt2-promoted concise synthesis of difluoroboron-derivatized curcumins from aldehydes and 2,4-pentanedione
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A concise and one-pot cascade method has been developed to achieve the synthesis of difluoroboron-derivatized curcumins (BF2C). Treatment of 2,4-pentanedione with BF3·OEt2, followed by condensation with aldehydes in the pr
- Liu, Kai,Chen, Jiangmin,Chojnacki, Jeremy,Zhang, Shijun
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p. 2070 - 2073
(2013/05/08)
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- Composition For The Prevention And Treatment Of Influenza Virus Infection And Composition For Suppressing Neuraminidase Activity Comprising Turmeric Extract
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Disclosed is a composition comprising a turmeric extract for preventing and treating influenza virus infection and for inhibiting neuraminidase activity. A turmeric extract, its fraction, and a curcuminoid-based compound separated therefrom may inhibit neuraminidase activity and have antiviral and cell degeneration inhibitory effects on influenza virus, and may be useful in preventing and treating influenza virus infection.
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- Curcumin is an inhibitor of calcium/calmodulin dependent protein kinase II
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Calcium/calmodulin dependent protein kinase II (CaMKII) is involved in the mechanisms underlying higher order brain functions such as learning and memory. CaMKII participates in pathological glutamate signaling also, since it is activated by calcium influx through the N-methyl-d-aspartate type glutamate receptor (NMDAR). In our attempt to identify phytomodulators of CaMKII, we observed that curcumin, a constituent of turmeric and its analogs inhibit the Ca2+-dependent and independent kinase activities of CaMKII. We further report that a heterocyclic analog of curcumin I, (3,5-bis[β-(4- hydroxy-3-methoxyphenyl)ethenyl]pyrazole), named as pyrazole-curcumin, is a more potent inhibitor of CaMKII than curcumin. Microwave assisted, rapid synthesis of curcumin I and its heterocyclic analogues is also reported.
- Mayadevi, M.,Omkumar, R. V.,Sherin, D. R.,Keerthi, V. S.,Rajasekharan, K. N.
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p. 6040 - 6047,8
(2020/08/20)
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- Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids
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A variety of novel aromatic and heterocyclic aromatic curcuminoids were synthesised, characterised and their anti-inflammatory activities (AIA) determined in vivo. Some of these compounds also were tested for inflammatory mediator production. The AIA of t
- Khan, M. Akram,El-Khatib, Riyad,Rainsford,Whitehouse
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experimental part
p. 30 - 38
(2012/03/26)
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- Synthesis, characterization and biological evaluation of succinate prodrugs of curcuminoids for colon cancer treatment
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A novel series of succinyl derivatives of three curcuminoids were synthesized as potential prodrugs. Symmetrical (curcumin and bisdesmethoxycurcumin) and unsymmetrical (desmethoxycurcumin) curcuminoids were prepared through aldol condensation of 2,4-pentanedione with different benzaldehydes. Esterification of these compounds with a methyl or ethyl ester of succinyl chloride gave the corresponding succinate prodrugs in excellent yields. Anticolon cancer activity of the compounds was evaluated using Caco-2 cells. The succinate prodrugs had IC50 values in the 1.8-9.6 μM range, compared to IC50 values of 3.3-4.9 μM for the parent compounds. Curcumin diethyl disuccinate exhibited the highest potency and was chosen for stability studies. Hydrolysis of this compound in phosphate buffer at pH 7.4 and in human plasma followed pseudo first-order kinetics. In phosphate buffer, the κobs and t1/2 for hydrolysis indicated that the compound was much more stable than curcumin. In human plasma, this compound was able to release curcumin, therefore our results suggest that succinate prodrugs of curcuminoids are stable in phosphate buffer, release the parent curcumin derivatives readily in human plasma, and show anti-colon cancer activity.
- Wichitnithad, Wisut,Nimmannit, Ubonthip,Wacharasindhu, Sumrit,Rojsitthisak, Pornchai
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experimental part
p. 1888 - 1900
(2011/04/25)
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- Biological evaluation of synthetic analogues of curcumin: Chloro-substituted-20-hydroxychalcones as potential inhibitors of tubulin polymerization and cell proliferation
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A series of chloro-substituted-20-hydroxychalcones were prepared and evaluated for their cytotoxic effects against K562 and SK-N-MC human cancer cell lines and as the inhibitors of tubulin polymerization. The 3,50-dichloro- analogue (compound 3) inhibited the assembly of protofilaments with 89% inhibition. Compound 3 was found to be bound to tubulin with a dissociation constant of 3.7 lM and altered far-UV circular dichroism spectrum of tubulin and altered far-UV circular dichroism spectrum of tubulin.
- Aryapour, Hassan,Riazi, Gholam Hossein,Foroumadi, Alireza,Ahmadian, Shahin,Shafiee, Abbas,Karima, Oveis,Mahdavi, Majid,Emami, Saeed,Sorkhi, Maedeh,Khodadady, Sirus
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body text
p. 503 - 510
(2012/04/11)
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- Reactions of reactive oxygen species (ROS) with curcumin analogues: Structure-activity relationship
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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 (O2?-?), singlet oxygen (1O2) and peroxyl radicals (CCl3O2 ?) and the bimolecular rate constants were determined. The DPPH radical reactions were followed by stopped-flow spectrometer, 1O2 reactions by transient luminescence spectrometer, and CCl3O 2? reactions using pulse radiolysis technique. The rate constants indicate that the presence of o-methoxy phenolic OH increases its reactivity with DPPH and CCl3O2?, while for molecules lacking phenolic OH, this reaction is very sluggish. Reaction of O2?-? and 1O2 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.
- Singh, Umang,Barik, Atanu,Singh, Beena G.,Priyadarsini, K. Indira
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body text
p. 317 - 325
(2012/01/14)
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- Antioxidant capacity of curcumin-directed analogues: Structure-activity relationship and influence of microenvironment
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Curcumin is the active ingredient of turmeric powder with a variety of biological activities including antioxidative activity. In order to find more active antioxidants with curcumin as the lead compound we synthesised a series of enone analogues of curcumin. The present work studied and compared the capacity of curcumin-directed analogues to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH{radical dot}) and protect human red blood cells (RBCs) from oxidative haemolysis. It was found that these compounds which bear o-diphenoxyl and o-dimethoxyphenoxyl groups exhibited significantly higher DPPH{radical dot}-scavenging and anti-haemolysis activities than those which bear no such groups. In contrast to curcumin analogues that retained the 7-carbon spacer, the compounds with a 5-carbon linker had lower activity. In the case of the latter, the introduction of a ring further decreased DPPH{radical dot}-scavenging activity. However, the introduction of a ring did increase anti-haemolysis activity, suggesting that the lipophilicity of these compounds might play an important role in the antioxidant activity.
- Shang, Ya-Jing,Jin, Xiao-Ling,Shang, Xian-Ling,Tang, Jiang-Jiang,Liu, Guo-Yun,Dai, Fang,Qian, Yi-Ping,Fan, Gui-Juan,Liu, Qiang,Zhou, Bo
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experimental part
p. 1435 - 1442
(2012/01/04)
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- Synthesis and identification of new 4-arylidene curcumin analogues as potential anticancer agents targeting nuclear factor-κB signaling pathway
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A series of curcumin analogues including new 4-arylidene curcumin analogues (4-arylidene-1,7-bisarylhepta-1,6-diene-3,5-diones) were synthesized. Cell growth inhibition assays revealed that most 4-arylidene curcumin analogues can effectively decrease the growth of a panel of lung cancer cells at submicromolar and low micromolar concentrations. High content analysis technology coupled with biochemical studies showed that this new class of 4-arylidene curcumin analogues exhibits significantly improved NF-κB inhibition activity over the parent compound curcumin, at least in part by inhibiting IκB phosphorylation and degradation via IKK blockage; selected 4-arylidene curcumin analogues also reduced the tumorigenic potential of cancer cells in a clonogenic assay.
- Qiu, Xu,Du, Yuhong,Lou, Bin,Zuo, Yinglin,Shao, Weiyan,Huo, Yingpeng,Huang, Jianing,Yu, Yanjun,Zhou, Binhua,Du, Jun,Fu, Haian,Bu, Xianzhang
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scheme or table
p. 8260 - 8273
(2011/02/21)
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- Phenolic and enolic hydroxyl groups in curcumin: Which plays the major role in scavenging radicals?
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The aim of this work is to clarify the antioxidant abilities of phenolic and enolic hydroxyl groups in curcumin. 1,7-Bis(4-benzyloxy-3-methoxyphenyl)-1, 6-heptadiene-3,5-dione (BEC), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol (OHC), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dlone (THC), and 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (BDC) are synthesized to determine the antioxidant activities by using antiradical assays against 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical, galvinoxyl radical, and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS?+) and by protecting DNA and erythrocyte against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) induced oxidation. The phenolic hydroxyl is the main group for curcumin to trap DPPH, galvinoxyl, and ABTS?+ radicals. The conjugative system between enolic and phenolic hydroxyl groups is beneficial for curcumin to protect erythrocytes against hemin-induced hemolysis and to protect DNA against AAPH-lnduced oxidation, but is not beneficial for curcumin to protect erythrocytes against AAPH-induced hemolysis. More hydroxyl groups enhance the antioxidant effectiveness of curcumin in the experimentel systems employed herein. Therefore, curcumin acts as an antioxidant through the phenolic hydroxyl group.
- Feng, Jian-Ying,Liu, Zai-Qun
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experimental part
p. 11041 - 11046
(2010/09/04)
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- Synthesis, cytotoxic and combined cDDP activity of new stable curcumin derivatives
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New curcumin derivatives are synthesized in order to improve chemical properties of curcumin. The aromatic ring glycosylation of curcumin provides more water-soluble compounds with a greater kinetic stability which is a fundamental feature for drug bioavailability. The glycosylation reaction is quite simple, low cost, with high yield and minimum waste. NMR data show that the ability of curcumin to coordinate metal ion, in particular Ga(III), is maintained in the synthesized products. Although the binding of glucose to curcumin reduces the cytotoxicity of the derivatives towards cisplatin (cDDP)-sensitive and -resistant human ovarian carcinoma cell lines, the compounds display a good selectivity since they are much less toxic against non-tumourigenic Vero cells. The combination of cDDP with the most active glycosyl-curcuminoid drug against both cDDP-sensitive and -resistant as well as against Vero cell lines is tested. The results show an improvement of cDDP efficacy with higher selectivity towards cancer cells than non-cancer cells. These studies indicate the need for developing new valid components of drug treatment protocols to cDDP-resistant cells as well.
- Ferrari, Erika,Lazzari, Sandra,Marverti, Gaetano,Pignedoli, Francesca,Spagnolo, Ferdinando,Saladini, Monica
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experimental part
p. 3043 - 3052
(2009/09/30)
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- Structure-activity relationship studies of curcumin analogues
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Two series of curcumin analogues, a total of twenty-four compounds, were synthesized and evaluated. The most potent compound, compound 23, showed potent growth inhibitory activities on both prostate and breast cancer lines with IC50 values in sub-micromolar range, fifty times more potent than curcumin. Curcumin analogues might be potential anti-tumor agents for breast and prostate cancers.
- Fuchs, James R.,Pandit, Bulbul,Bhasin, Deepak,Etter, Jonathan P.,Regan, Nicholas,Abdelhamid, Dalia,Li, Chenglong,Lin, Jiayuh,Li, Pui-Kai
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scheme or table
p. 2065 - 2069
(2009/11/30)
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- Method for the Synthesis of Curcumin Analogues
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The present invention relates to improved methods for achieving the synthesis of 1,7-diaryl-1,6-heptadiene-3,5-diones, and in particular curcumin and its analogues. The invention provides a process for synthesizing such compounds in substantial yield and purity using environmentally benign processes and materials. The invention also relates to the use of such synthesized products in the treatment of Alzheimer's Disease and other diseases.
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Page/Page column 6-7
(2008/06/13)
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- CURCUMIN SYNTHESIS
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Process for the preparation of curcumin by condensation of vanillin with acetylacetone in the presence of boric acid and an aliphatic or araliphatic amine in a highly polar, aprotic solvent, under concomitant removal of water.
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Page/Page column 5
(2008/06/13)
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- Method and compounds for cancer treatment utilizing NFkB as a direct or ultimate target for small molecule inhibitors
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A method is described for cancer treatment through NFκB inhibition. NFκB is a direct or ultimate target for small molecule inhibitors. These small molecule inhibitors are aimed at suppression of NFκB directly or by indirect suppression of IKK, SFK kinases, or other upstream kinases. The present invention includes small molecule inhibitors comprising three, five, and seven carbon unsaturated spacers having one or two carbonyls, flanked by substituted aryl rings. The small molecule inhibitors can be symmetrical or unsymmetrical.
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Page/Page column 4; sheet 1
(2008/06/13)
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- Methods for treating neural disorders and conditions, and compounds useful therefor
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In accordance with the present invention, there are provided novel compounds that protect neurons and/or promote neuroregeneration and/or promote memory formation. Such compounds are useful for treatment of a variety of neural disorders and conditions. In another aspect of the present invention, there are also provided formulations containing one or more of the above-described compounds, optionally further containing additional neurologically active compound(s) and/or adjuvants to facilitate delivery thereof across the blood/brain barrier. In still another aspect of the present invention, there are further provided methods for treating a wide variety of neurological indications, e.g., acute neural injuries, chronic injuries, promoting memory formation, and the like.
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Page/Page column 2
(2008/06/13)
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- Synthesis and biological evaluation of polyhydroxycurcuminoids
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A series of curcumin analogs (1-3, 5a-5t) was synthesized through the condensation of appropriately protected hydroxybenzaldehydes with acetylacetone, followed by deprotection. The antioxidant activity of these analogs was determined by superoxide free radical nitroblue tetrazolium and DPPH free radical scavenging methods and the polyhydroxycurcuminoids (5l-5s) displayed excellent antioxidant activity. These analogs showed cytotoxicity to lymphocytes and promising tumor-reducing activity on Dalton's lymphoma ascites tumor cells.
- Venkateswarlu, Somepalli,Ramachandra, Marellapudi S.,Subbaraju, Gottumukkala V.
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p. 6374 - 6380
(2007/10/03)
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- Anti-oxidant activities of curcumin and related enones
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The natural product curcumin (diferuloylmethane, 1,7-bis(4-hydroxy-3- methoxyphenyl)-1,6-heptadiene-3,5-dione), obtained from the spice turmeric, exhibits numerous biological activities including anti-cancer, anti-inflammatory, and anti-angiogenesis activities. Some of these biological activities may derive from its anti-oxidant properties. There are conflicting reports concerning the structural/electronic basis of the anti-oxidant activity of curcumin. Curcumin is a symmetrical diphenolic dienone. A series of enone analogues of curcumin were synthesized that included: (1) curcumin analogues that retained the 7-carbon spacer between the aryl rings; (2) curcumin analogues with a 5-carbon spacer; and (3) curcumin analogues with a 3-carbon spacer (chalcones). These series included members that retained or were devoid of phenolic groups. Anti-oxidant activities were determined by the TRAP assay and the FRAP assay. Most of the analogues with anti-oxidant activity retained the phenolic ring substituents similar to curcumin. However, a number of analogues devoid of phenolic substituents were also active; these non-phenolic analogues are capable of forming stable tertiary carbon-centered radicals.
- Weber, Waylon M.,Hunsaker, Lucy A.,Abcouwer, Steve F.,Deck, Lorraine M.,Vander Jagt, David L.
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p. 3811 - 3820
(2007/10/03)
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