- Preparation method 1,7 - di (4 -hydroxy) heptyl -3-5 - glycol ester
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The invention discloses a preparing method of 1,7-bis(4-benzene hydroxyl)heptyl-3,5-glycol ester. The method includes the following steps of firstly, conducting a -C=C- reduction reaction with bisdemethoxycurcumin as the raw material to obtain a product 3; secondly, conducting a reduction reaction of carbonyl on the premise of protecting hydroxyl on a benzene ring to obtain a product 5; secondly,conducting an esterification reaction on the product 5 to obtain a product 6, and conducting a protecting group removing reaction on the product 6 to obtain the final product, namely 1,7-bis(4-benzenehydroxyl)heptyl-3,5-glycol ester. By means of the method, through the reduction reaction, the reaction of protecting hydroxyl on the benzene ring, the reaction of reducing carbonyl, the esterification reaction and the protecting group removing reaction, 1,7-bis(4-benzene hydroxyl)heptyl-3,5-glycol ester can be obtained; the reaction process is simple, operation is simple, applied raw materials are low in cost, yield is high, and the method is suitable for industrially producing 1,7-bis(4-benzene hydroxyl)heptyl-3,5-glycol ester on a large scale.
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Paragraph 0026; 0035; 0037; 0039-0040
(2021/01/30)
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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 0026-0027; 0031-0032; 0050-0052
(2020/05/30)
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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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- Synthesis, spectral characterization and thermal analysis of rubrocurcumin and its analogues
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Rubrocurcumin and its analogues were synthesized and characterized by UV, IR, NMR and FT-MS spectral data. Thermal analysis of compounds has been carried out using TG-DTG techniques using non-isothermal heating conditions. Flynn–Wall–Ozawa and Kissinger–Akahira–Sunose isoconversional methods were used to determine the apparent activation energies (Ea) for the thermal decomposition rubrocurcumin and its analogues. The Ea values obtained using these methods were used as reference to determine the most suitable kinetic model using Coats–Redfern method. A possible mechanism is suggested to explain the thermal decomposition process. From the TG-DTG data, kinetic parameters have been calculated and were used to evaluate the thermal stability of compounds and the substituent effect on its thermal stability.
- John, Jeena,Devi, R. Sudha,Balachandran,Babu, K. V. Dinesh
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p. 2301 - 2314
(2017/10/06)
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- 3,3′-OH curcumin causes apoptosis in HepG2 cells through ROS-mediated pathway
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In this paper, we synthesized a series of curcumin analogs and evaluated their cytotoxicity against HepG2 cells. The results exhibited that the hydroxyl group at 3,3′-position play an essential role in enhancing their anti-proliferation activity. More importantly, 3,3′-hydroxy curcumin (1b) caused apoptosis in HepG2 cells with the ROS generation, which may be mainly composed of hydroxyl radicals (HO[rad]) and H2O2. The more cytotoxic activity and ROS-generating ability of 1b may be due to the more stable in (RPMI)-1640 medium and more massive uptake than curcumin. Then the generation of ROS can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 3,3′-hydroxy curcumin (1b) may cause HepG2 cells apoptosis through ROS-mediated pathway, but also offer an important information for design of curcumin analog.
- Liu, Guo-Yun,Sun, Yong-Zheng,Zhou, Na,Du, Xiu-Mei,Yang, Jie,Guo, Shang-Jing
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p. 157 - 163
(2018/05/25)
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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
-
-
- Synthesis and cytotoxic activities of a curcumin analogue and its bis-Mannich derivatives
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Mannich bases (2-6) of curcumin analogue 1, [1,5-bis(4-hydroxy-phenyl)penta-1,4-dien-3-one], were synthesized.Their cytotoxicity against human HL-60 promyelocytic leukemia and HSC-2, HSC-3, and HSC-4 oral squamous carcinoma cell lines, as well as against normal oral cells was evaluated. Mannich bases 2-5 displayed more potent cytotoxicity than curcumin and curcumin analogue 1 towards malignant cells with high PSE values (93.7-136.6). PARP1 cleavage assay demonstrated the induction of apoptosis of HSC-2 cells by the most potent and tumor selective compound 4, which is a bis Mannich base having N-methyl piperazine moieties. The results obtained suggest that preparation of Mannich bases of a curcumin analogue 1 was a useful chemical modification for cytotoxicity and tumour-selectivity for the compounds synthesized, and apoptosis can be one of the possible mechanisms of action for the cytotoxicity.
- Yerdelen, Kadir Ozden,Gul, Halise Inci,Sakagami, Hiroshi,Umemura, Naoki,Sukuroglu, Murat
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p. 643 - 649
(2015/09/01)
-
- Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes of curcuminoids
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Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc-tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4) (4), of 4′-ferrocenyl-2,2′: 6′,2″-terpyridine (Fc-tpy) and 4′-phenyl-2,2′:6′, 2″-terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo-induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc+/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay.
- Balaji, Babu,Balakrishnan, Babita,Perumalla, Sravanakumar,Karande, Anjali A.,Chakravarty, Akhil R.
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p. 458 - 467
(2014/11/08)
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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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- Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor
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Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed.
- Endo, Hitoshi,Nikaido, Yuri,Nakadate, Mamiko,Ise, Satomi,Konno, Hiroyuki
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supporting information
p. 5621 - 5626
(2015/01/08)
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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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- 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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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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- METHOD TO PREPARE PURE CURCUMIN
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This invention describes a preparation of at least 99% by weight pure curcumin from less pure grades of curcumin utilizing phenol protecting groups to favor a selective recrystallization of curcumin in the presence of demethoxycurcumin and bis-demethoxycurcumin and other curcuminoids of minor composition.
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Page/Page column 4-5
(2010/03/31)
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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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- Different curcuminoids inhibit T-lymphocyte proliferation independently of their radical scavenging activities
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Purpose. We investigated the inhibitory effects of curcumin, curcumin derivatives and degradation products on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation and the role of their radical scavenging activity. Methods. OKT3-induced human PBMC proliferation was determined by measuring 3H-thymidine incorporation. Radical scavenging activity was evaluated by using an in vitro DPPH assay. Results. OKT3-induced PBMC proliferation was inhibited by curcumin, isocurcumin, bisdesmethoxy-, diacetyl-, tetrahydro-, hexahydro-, and octahydrocurcumin as well as by vanillin, ferulic acid, and dihydroferulic acid with IC50-values of 2.8, 2.8, 6.4, 1.0, 25, 38, 82, 729, 457, and >1,000 μM, respectively. The investigated substances with the strongest effect on radical scavenging were tetrahydro-, hexahydro-, and octahydrocurcumin with IC50 values of 10.0, 11.7, and 12.3 μM, respectively. IC50-values of dihydroferulic acid, ferulic acid, and curcumin were 19.5, 37, and 40 μM. The substances with the lowest radical scavenging activities were vanillin, isocurcumin, diacetylcurcumin, and bisdesmethoxycurcumin with IC50 values higher than 100 μM each. Conclusions. Curcuminoid-induced inhibition of OKT3-induced PBMC proliferation depends on the number of carbon atoms and double bonds of the 1,6-heptadiene-3,5-dione structure as well as on the phenolic ring substitutes of the curcuminoids but is not correlated to their respective radical scavenging activity.
- Deters, Michael,Knochenwefel, Heiko,Lindhorst, Daniel,Koal, Therese,Meyer, Hartmut H.,Haensel, Wolfram,Resch, Klaus,Kaever, Volkhard
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p. 1822 - 1827
(2008/09/21)
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- PROCESS FOR PRODUCING ENRICHED FRACTIONS OF TETRAHYDROXYCURCUMIN AND TETRAHYDROTETRAHYDROXY-CURCUMIN FROM THE EXTRACTS OF CURCUMA LONGA
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A process for producing an enriched fraction of tetrahydoxycurcumin containing, tetrahydroxycurcumin, demethylcurcumin, demethylmonodemethoxycurcumin and bisd.emethoxycurcumin and colorless tetrahydroderivatives thereof. The process consists of demethylation of natural curcumins, obtained, in turn, from the organic solvent extract of turmeric from Curcuma species. The said enriched fraction of tetrahydroxycurcumin is subjected to hydrogenation to get colorless tetrahydrotetrahydroxycurcumin enriched fraction. The enriched fractions of tetrahydroxycurcumin and colorless tetrahydrotetrahydroxycurcumin exhibits potent antioxidative action and reduces inflammation.
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Page/Page column 11-12
(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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- 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)
-
- Synthesis of Curcumin Analogues as Potential Antioxidant, Cancer Chemopreventive Agents
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New series of 3,5-bis(substituted benzylidene)-4-piperidones, 2,7-bis(substituted benzylidene)cycloheptanones, 1,5-bis(substituted phenyl)-1,4-pentadien-3-ones, 1,7-bis(substituted phenyl)-1,6-heptadien-3,5-diones, 1,1-bis(substituted cinnamoyl)-cyclopentanes, and 1,1-bis(substituted cinnamoyl)cyclohexanes have been synthesized and tested for their antioxidant activity. Among the tested compounds, compounds II 4, II9 II10, II11, V1, and V4 exhibited higher free radical scavenger activity with % inhibition values of 90.71, 91.24, 96.91, 94.26, 99.23, and 99.85%, respectively. Moreover, compound V1 is the safest member toward peripheral multinuclear neutrophils (PMNs) with a % viability value of 91%. Detailed synthesis, spectroscopic, and biological data are reported.
- Youssef, Khairia M.,El-Sherbeny, Magda A.,El-Shafie, Faiza S.,Farag, Hassan A.,Al-Deeb, Omar A.,Awadalla, Sit Albanat A.
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-
- Cytotoxicity of curcuminoids and some novel compounds from Curcuma zedoaria
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Bioassay-directed fractionation of an EtOH extract of Curcuma zedoaria led to isolation of an active curcuminoid, which was identified as demethoxycurcumin (2) by comparison of its 1H and 13C NMR spectra with literature data and by direct comparison with synthetic material. Curcumin (1) and bisdemethoxycurcumin (3) were also obtained. Curcuminoids (1-3) were synthesized and demonstrated to be cytotoxic against human ovarian cancer OVCAR-3 cells. The observed CD50 values of 1, 2, and 3 were 4.4, 3.8, and 3.1 μg/mL, respectively. Three additional novel compounds, 3,7- dimethylindan-5-carboxylic acid (4), curcolonol (5), and guaidiol (6), were also isolated from the EtOH extract. The structures and relative stereochemistry of 4-6 were determined by spectroscopic methods and X-ray crystallographic analysis.
- Syu,Shen,Don,Ou,Lee,Sun
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p. 1531 - 1534
(2007/10/03)
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- Curcumin analogs with altered potencies against HIV-1 integrase as probes for biochemical mechanisms of drug action
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We have previously reported the inhibitory activity of curcumin against human immunodeficiency virus type one (HIV-1) integrase. In the present study, we have synthesized and tested analogs of curcumin to explore the structure-activity relationships and mechanism of action of this family of compounds in more detail. We found that two curcumin analogs, dicaffeoylmethane (6) and rosmarinic acid (9), inhibited both activities of integrase with IC50 values below 10 μM. We have previously demonstrated that lysine 136 may play a role in vital DNA binding. We demonstrated equivalent potencies of two curcumin analogs against both this integrase mutant and wild-type integrase, suggesting that the curcumin-binding site and the substrate-binding site may not overlap. Combining one curcumin analog with the recently described integrase inhibitor NSC 158393 resulted in integrase inhibition which was synergistic, reflective of drug-binding sites which may not overlap. We have also determined that these analogs can inhibit binding of the enzyme to the viral DNA but that this inhibition is independent of divalent metal ion. Furthermore, kinetic studies of these analogs suggest that they bind to the enzyme at a slow rate. These studies can provide mechanistic and structural information which may guide the future design of integrase inhibitors.
- Mazumder, Abhijit,Neamati, Nouri,Sunder, Sanjay,Schulz, Jutta,Pertz, Heinz,Eich, Eckart,Pommier, Yves
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p. 3057 - 3063
(2007/10/03)
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