- Full structural characterization of homoleptic complexes of diacetylcurcumin with Mg, Zn, Cu, and Mn: Cisplatin-level Cytotoxicity in Vitro with Minimal Acute Toxicity in Vivo
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At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the β-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the β-diketone function, while the 1H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 μM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)2Mg), or ca. 2-fold higher ((DAC)2Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds.
- Meza-Morales, William,Mirian Estévez-Carmona,Alvarez-Ricardo, Yair,Obregón-Mendoza, Marco A.,Cassani, Julia,Ramírez-Apan, María Teresa,Escobedo-Martínez, Carolina,Soriano-García, Manuel,Reynolds, William F.,Enríquez, Raúl G.
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Read Online
- Inhibition of amyloid fibril formation of β-lactoglobulin by natural and synthetic curcuminoids
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The aggregation of proteins has been associated with several aspects of daily life, including food processing, blood coagulation and many neurodegenerative infections. However, the actual mechanisms responsible for amyloidosis, the irreversible fibril for
- Maity, Sanhita,Pal, Sampa,Sardar, Subrata,Sepay, Nayim,Parvej, Hasan,Begum, Shahnaz,Dalui, Ramkrishna,Das, Niloy,Pradhan, Anirban,Halder, Umesh Chandra
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Read Online
- Synthesis and characterization of acetyl curcumin-loaded core/shell liposome nanoparticles via an electrospray process for drug delivery, and theranostic applications
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Despite substantial advancements in divergent drug delivery systems (DDS), there is still room for novel and innovative nanoparticle-mediated drug delivery methodologies such as core/shell liposomes to deliver drugs in a kinetically controlled manner into
- Reddy, Ankireddy Seshadri,Lakshmi, Buddolla Anantha,Kim, Sanghyo,Kim, Jongsung
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Read Online
- Efficient esterification of curcumin in bis(trifluoromethylsulfonyl)imide-based ionic liquids
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In this paper, the potential application of bis(trifluoromethylsulfonyl)imide based ionic liquids paired with various cations (ammonium, piperidinium, pyridinium and imidazolium) as the recyclable reaction media for the esterification of curcumin has been
- Gano, Marcin,Klebeko, Joanna,Pe?ech, Robert
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Read Online
- Preparation method of tetrahydrocurcumin and intermediate thereof
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The invention provides a preparation method of tetrahydrocurcumin and an intermediate thereof, and the preparation method of the intermediate comprises the following steps: step a, in the presence ofalkali, reacting a compound (IV) with an acetylation reagent in a solvent to obtain a compound (III); b, in the presence of a catalyst and a solvent, the compound (III) and hydrogen or a hydrogen donor are subjected to a reduction reaction to obtain a compound (II), namely the tetrahydrocurcumin intermediate; and the tetrahydrocurcumin preparation method comprises the step that acetyl is removed from the compound (II) in the solvent in the presence of alkali to obtain a compound (I), namely tetrahydrocurcumin. The selectivity of the diacetyl curcumin reduction reaction is far superior to thatof direct reduction of curcumin, and the yield is high; the method is simple and convenient in purification and high in product content, and hardly contains curcumin, hexahydrocurcumin and octahydrocurcumin; the method disclosed by the invention is simple and feasible to operate, stable and durable in process, easy to control, easy to amplify and convenient in post-reaction treatment, and can be economically and conveniently used for industrial production.
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Paragraph 0028-0031; 0033-0036; 0038-0041; 0043-0046
(2020/05/01)
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- Synthesis, antifungal evaluation and molecular docking studies of some tetrazole derivatives
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A facile and simple protocol for the [3+2] cycloaddition of alkyl nitriles (RCN) with sodium azide (NaN3) in the presence of copper bis(diacetylcurcumin) 1,2-diamin-obenzene Schiff base complex, SiO2-[Cu-BDACDABSBC] as a heterogeneous catalyst in the presence of ascorbic acid and a solution of water/i-PrOH (50:50, V/V) media at reflux condition is described. The supported catalyst was prepared by immobilization of a copper bis(diacetylcurcumin) 1,2-diaminobenzene Schiff base complex [Cu-BDACDABSBC] on silica gel. The complex has high selectivity, catalytic activity, and recyclability. The significant features of this procedure are high yields, broad substrate scope and simple and efficient work-up procedure. According to this synthetic methodology, excellent yields of 5-substituted 1H-tetrazoles having bioactive N-heterocyclic cores were synthesized. The in vitro antifungal activities of title compounds were screened against various pathogenic fungal strains, such as Candida species involving C. albicans, C. glabrata, C. krusei, C. parapsilosis as well as filamentous fungi like Aspergillus species consisting of A. fumigatus and A. flavus. The molecular docking analysis is discussed for one most potent compound against fungi. The docking study determined a remarkable interaction between the most potent compounds and the active site of Mycobacterium P450DM.
- Afsarian, Mohammad Hosein,Farjam, Mojtaba,Zarenezhad, Elham,Behrouz, Somayeh,Rad, Mohammad Navid Soltani
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p. 874 - 887
(2020/01/21)
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- Use of curcumin derivative
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The invention provides the use of a curcumin derivative. The use of the curcumin derivative shown in a formula I (please see the specification for the formula), or salts of the curcumin derivative inthe preparation of drugs of anti-inflammatory diseases and/or a COX inhibitor is particularly provided. The curcumin derivative has good COX inhibitory activity and anti-inflammatory activity and canbe used for preparing the COX inhibitor and anti-inflammatory drugs. Compound 6 and compound 7 have the best effects on COX-2 inhibitory activity and anti-inflammatory activity and can be used for preparing a COX-2 inhibitor and the anti-inflammatory drugs.
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Paragraph 0039-0042; 0047
(2019/10/23)
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- Method for restraining proliferation of tumor cells through cooperation of 4,4-dimethyl curcumin with ultrasonic
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The invention relates to a method for restraining proliferation of tumor cells through cooperation of 4,4-dimethyl curcumin with ultrasonic, and belongs to the technical field of medicine. The proliferation of the tumor cells is restrained through coopera
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Paragraph 0022; 0023; 0024
(2019/08/01)
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- Four mammalian keratinous analogue and its preparation and use
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The invention belongs to the technical field of medical technology and relates to a series of tetrahydrocurcumin analogues, a preparation and an application thereof. The tetrahydrocurcumin analogue is characterized by having a structure represented as for
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Paragraph 0020; 0026; 0027
(2017/08/25)
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- Synthesis of curcuminoids and evaluation of their cytotoxic and antioxidant properties
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Curcumin (1) and ten derivatives (2-11) were synthesized and evaluated as cytotoxic and antioxidant agents. The results of primary screening by Sulforhodamine B assay against five human cancer cell lines (U-251 MG, glioblastoma; PC-3, human prostatic; HCT-15, human colorectal; K562, human chronic myelogenous leukemia; and SKLU-1, non-small cell lung cancer) allowed us to calculate the half maximal inhibitory concentration (IC50) values for the more active compounds against HCT-15 and K562 cell lines. Compounds 2 and 10 were the most active against both cell lines and were more active than curcumin itself. Thiobarbituric acid reactive substances (TBARS) assay showed that 7 has potent activity; even stronger than curcumin, α-tocopherol, and quercetin.
- Lozada-García, María Concepción,Enríquez, Raúl G.,Ramírez-Apán, Teresa O.,Nieto-Camacho, Antonio,Palacios-Espinosa, Juan Francisco,Custodio-Galván, Zeltzin,Soria-Arteche, Olivia,Pérez-Villanueva, Jaime
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- Curcumin analogues and preparation and application thereof
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The invention belongs to the field of medical technology and relates to preparation and application of a series of curcumin analogues. The curcumin analogues have structures as shown in the formula I, formula II and formula III, wherein R, R1 and R2 are a
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Paragraph 0125; 0126
(2016/10/07)
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- A three-enzyme-system to degrade curcumin to natural vanillin
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The symmetrical structure of curcumin includes two 4-hydroxy-3-methoxyphenyl substructures. Laccase catalyzed formation of a phenol radical, radical migration and oxygen insertion at the benzylic positions can result in the formation of vanillin. As vanillin itself is a preferred phenolic substrate of laccases, the formation of vanillin oligomers and polymers is inevitable, once vanillin becomes liberated. To decelerate the oligomerization, one of the phenolic hydroxyl groups was protected via acetylation. Monoacetyl curcumin with an approximate molar yield of 49% was the major acetylation product, when a lipase from Candida antarctica (CAL) was used. In the second step, monoacetyl curcumin was incubated with purified laccases of various basidiomycete fungi in a biphasic system (diethyl ether/aqueous buffer). A laccase from Funalia trogii (LccFtr) resulted in a high conversion (46% molar yield of curcumin monoacetate) to vanillin acetate. The non-protected vanillin moiety reacted to a mixture of higher molecular products. In the third step, the protecting group was removed from vanillin acetate using a feruloyl esterase from Pleurotus eryngii (PeFaeA) (68% molar yield). Alignment of the amino acid sequences indicated that high potential laccases performed better in this mediator and cofactor-free reaction.
- Esparan, Vida,Krings, Ulrich,Struch, Marlene,Berger, Ralf G.
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p. 6640 - 6653
(2015/05/06)
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- Synthesis and antiproliferative effect of novel curcumin analogues
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Novel curcumin analogues with α,β-unsaturated ketone moiety and/or α,β-saturated ketone structure were synthesized from curcumin via alkylation at the central carbon and the phenolic hydroxy groups, and hydrogenation of α,β-unsaturated ketone moiety. The antiproliferative activities were tested in five human solid tumor cell lines in vitro. Most of the compounds exhibited increased antiproliferative activities comparing with that of curcumin. Structure-activity relationship (SAR) analysis revealed that the α,β-unsaturated ketone structure was not required for antiproliferative activity of these curcumin analogues. Among these compounds, 1,7-bis(3-methoxy-4-(3-(4-methylpiperazinyl-1-yl)propoxy)phenyl)-4, 4-dibenzylheptane-3,5-dione (16f) was the most effective one with IC 50 value below 1μM, which was 9- to 81-fold more potent than curcumin.
- Liu, Bingmi,Xia, Mingyu,Ji, Xiaoling,Xu, Liying,Dong, Jinhua
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p. 757 - 763
(2013/07/26)
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- Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species
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The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1:1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Trypanosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC50 for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 μM, respectively). Among 43 curcuminoid analogs and 8 pairs of 1:1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in submicromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one (40) was the most active compound, with an EC50 value of 0.053 ± 0.007 μM; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC50 0.12 ± 0.01 μM). Using a previously characterized diminazene-resistant T. b. brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against T. b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC50 values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16 ± 3 and 37 ± 6 μM, respectively) while the control drug, pentamidine, displayed an EC50 of 16 ± 2 μM. Among the active curcuminoid analogs, four compounds exhibited EC50 values of less than 5 μM against Leishmania major promastigotes and four against L. mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T. b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T. b. brucei ranged from 3-fold to 1500-fold. The selectivity index for the most active analog, the enone 40, was 453-fold.
- Changtam, Chatchawan,de Koning, Harry P.,Ibrahim, Hasan,Sajid, M. Sohail,Gould, Matthew K.,Suksamrarn, Apichart
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experimental part
p. 941 - 956
(2010/04/24)
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- Isoxazole analogs of curcuminoids with highly potent multidrug-resistant antimycobacterial activity
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Curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3), the curcuminoid constituents of the medicinal plant Curcuma longa L., have been structurally modified to 55 analogs and antimycobacterial activity against Mycobacterium tuberculosis has been evaluated. Among the highly active curcuminoids, the isoxazole analogs are the most active group, with mono-O-methylcurcumin isoxazole (53) being the most active compound (MIC 0.09 μg/mL). It was 1131-fold more active than curcumin (1), the parent compound, and was approximately 18 and 2-fold more active than the standard drugs kanamycin and isoniazid, respectively. Compound 53 also exhibited high activity against the multidrug-resistant M. tuberculosis clinical isolates, with the MICs of 0.195-3.125 μg/mL. The structural requirements for a curcuminoid analog to exhibit antimycobacterial activity are the presence of an isoxazole ring and two unsaturated bonds on the heptyl chain. The presence of a suitable para-alkoxyl group on the aromatic ring which is attached in close proximity to the nitrogen function of the isoxazole ring and a free para-hydroxyl group on another aromatic ring enhances the biological activity.
- Changtam, Chatchawan,Hongmanee, Poonpilas,Suksamrarn, Apichart
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experimental part
p. 4446 - 4457
(2010/10/19)
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- Synthesis and exploration of novel curcumin analogues as anti-malarial agents
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Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC50 of ~3.25 μM (MIC = 13.2 μM) and IC50 4.21 μM (MIC = 14.4 μM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparumgrowth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC50 of 0.48, 0.87, 0.92 μM and CQ-R P. falciparum at IC50 of 0.45 μM, 0.89, 0.75 μM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.
- Mishra, Satyendra,Karmodiya, Krishanpal,Surolia, Namita,Surolia, Avadhesha
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p. 2894 - 2902
(2008/09/19)
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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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- Design, development and synthesis of mixed bioconjugates of piperic acid-glycine, curcumin-glycine/alanine and curcumin-glycine-piperic acid and their antibacterial and antifungal properties
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In the present communication different curcumin bioconjugates viz. 4,4′-di-O-glycinoyl-curcumin, 4,4′-di-O-d-alaninoyl-curcumin, 4,4′-di-O-(glycinoyl-di-N-piperoyl)-curcumin, 4,4′-di-O-piperoyl curcumin, curcumin-4,4′-di-O-β-D-glucopyranoside, 4,4′-di-O-acetyl-curcumin along with piperoyl glycine, have been synthesised and characterised by spectra UV, 1H NMR and elemental analysis. All the covalent bonds used are biodegradable. This makes these derivatives as potent prodrugs, which can get hydrolysed at the target sites. These bioconjugates were tested in vitro against different bacteria and fungi. The 4,4′-di-O-(glycinoyl-di-N-piperoyl)-curcumin and 4,4′-di-O- acetyl-curcumin are more effective than Cefepime, an antibacterial drug available in market, at the same concentration. The 4,4′-di-O-(glycinoyl- di-N-piperoyl)-curcumin and 4,4′-di-O-piperoyl curcumin had antifungal activity in vitro almost comparable with fluconazole, the most popular antifungal drug. The enhanced activity of these bioconjugates vis-a-vis the parent molecule that is curcumin may be due to improved cellular uptake or reduced metabolism of these bioconjugates resulting in building up of enough concentration inside the infected cells. It opens a new era for exploring suitably designed curcumin bioconjugates as potential antibacterial/antifungal drugs.
- Mishra, Satyendra,Narain, Upma,Mishra, Roli,Misra, Krishna
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p. 1477 - 1486
(2007/10/03)
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- Synthesis and structure of new heterocyclic derivatives of curcumin
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New heterocyclic derivatives of curcumin (3) of different ring size were synthesized by reaction of a key intermediate, 1,7-bis(4-acetoxy-3-methoxyphenyl)hepta-3,5-dione (5) with some bi-nucleophilic molecules. These new synthetic derivatives were obtaine
- Concepcion Lozada,Enriquez, Raul G.,Lobato, Carlos E.,Ortiz, Benjamin,Soriano, Manuel,Gnecco, Dino,Reynolds, William F.
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- NOVEL CURCUMIN/TETRAHYDROCURCUMIN DERIVATIVES FOR USING IN COSMETICS, PHARMACEUTICALS AND FOR NUTRITION
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The invention relates to novel curcumin/tetrahydrocurcumin esters and the use thereof for producing cosmetic, dermatological or pharmaceutical preparations, food supplements, additives for food supplements, and foodstuff or animal feed compositions. Said
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(2008/06/13)
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