- Mesophase behavior and DFT conformational analysis of new symmetrical diester chalcone liquid crystals
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Synthesis, geometrical structures, conformational analysis, mesomorphic and optical characterizations of new angular chalcone liquid crystals, 4-(1,5-(3-oxopenta-1,4-dienyl))diphenyl bis-4-alkoxybenzoates, were investigated. These compounds contain chalcone core and diester phenyl rings attached to symmetrical terminal alkoxy chains with different number (n) of carbons from 6 to 16. Mesomorphic and optical properties were studied for the prepared homologues by differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Elemental analyses, FT-IR, 1H, and 13C NMR spectroscopy were used for molecular structure confirmation. Density functional theory (DFT) theoretical calculations were estimated to confirm the experimental data and to deduce the most stable confirmal of prepared compounds. The results indicate that the stability of the conformers and the type of the mesophase are dependent on the length of the terminal alkoxy chains. Thermal parameters, dipole moments and polarizability of all estimated conformers were discussed. The relationships between the values of these parameters and the conformer type as well as the mesophase stability were illustrated.
- Hagar,Ahmed,El-Sayed,Alnoman
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Read Online
- Method for efficiently synthesizing 1, 5-bis (4-hydroxyphenyl)-1, 4-pentadiene-3-ketone
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The invention discloses a method for efficiently synthesizing 1, 5-di (4hydroxyphenyl)-1, 4-pentadiene-3-ketone, and belongs to the field of organic chemical synthesis. According to the method, a ClaisenSchmidt reaction is carried out, p-hydroxybenzaldehyde and acetone are taken as reactants, boron trifluoride diethyl ether is taken as a catalyst, acetone and part of the catalyst are simultaneously and gradually added into p-hydroxybenzaldehyde separately, a drying agent is added into a reaction system, so that side reactions are effectively inhibited, and the reaction is optimized to obtain the product. After the reaction is finished, the product solution is dropwise added into deionized water, precipitates are collected, and the precipitates are dried. The method is simple in process andeasy to implement, can realize high-selectivity (purity is greater than or equal to 98%) and high-yield (greater than or equal to 95%) synthesis of 1, 5-di (4hydroxy phenyl)-1, 4-pentadiene-3-ketone,solves the problems of single-ended substitution and low yield all the time, and has important practical application value.
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Paragraph 0012; 0025-0032
(2021/01/11)
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- Supramolecular polymeric aggregation behavior and its impact on catalytic properties of imidazolium based hydrophilic ionic liquids
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Ionic Liquids (ILs) self-assemble to form supramolecular polymeric clusters/aggregates. The aggregation behavior of ILs influences its activity in the organic synthesis. However, the precise role of ILs in organic reactions is still unknown. It is, therefore, important to comprehend the supramolecular polymeric aggregation behavior of ILs. We are exploring the supramolecular polymeric aggregation behavior of ILs using Electrospray Ionization Mass Spectrometry (ESI-MS). We have synthesized four hydrophilic ILs (1–4) and investigated their aggregation behavior and its impact on catalytic activity in Carbon-Carbon bond formation (Knoevenagel and Claisen-Schmidt condensation). Here, we show that the aggregation behavior of ILs depends on the type and nature of cation and anion. ESI-MS (?ve) spectra reveals two different type of aggregation i.e. [CnAn+1]? & [A2 + H+]?. We have found that catalytic activity increases with increased [CnAn+1]? supramolecular aggregation. Consequently, highest yield of products obtained in ILs which show decreased anion-anion aggregation [A2 + H+]? abundance in ESI-MS. We anticipate our results to be a starting point for the establishment of desired ILs for organic synthesis.
- Muhammad, Shoaib,Javed, Muhammad Naveed,Ali, Firdous Imran,Bari, Ahmed,Hashmi, Imran Ali
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- Electrospray ionization tandem mass spectrometry of monoketone curcuminoids
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Rationale: Although monoketone curcuminoids (MKCs) have been largely investigated due to their biological activities, data on the gas-phase fragmentation reactions of protonated MKCs under collision-induced dissociation (CID) conditions are still scarce. Here, we combined electrospray ionization tandem mass spectrometry (ESI-MS/MS) data, multiple-stage mass spectrometry (MSn), deuterium exchange experiments, accurate-mass data, and thermochemical data estimated by computational chemistry to elucidate and to rationalize the fragmentation pathways of eleven synthetic MKCs. Methods: The MKCs were synthesized by Claisen-Schmidt condensation under basic (1–9) or acidic (10–11) conditions. ESI-CID-MS/MS analyses and deuterium-exchange experiments were carried out on a triple quadrupole mass spectrometer. MSn analyses on an ion trap mass spectrometer helped to elucidate the fragmentation pathways. Accurate-mass data and thermochemical data, obtained at the B3LYP/6–31+G(d,p) level of theory, were used to support the ion structures. Results: The most intense product ions were the benzyl ions ([C7H2R1R2R3R4R5]+) and the acylium ions ([M + H ? C8H3R1R2R3R4R5]+), which originated directly from the precursor ion as a result of two competitive hydrogen rearrangements. Product ions [M + H – H2O]+ and [M + H ? C6HR1R2R3R4R5]+, which are formed after Nazarov cyclization, were also common to all the analyzed compounds. In addition, ?Br and ?Cl eliminations were diagnostic for the presence of these halogen atoms at the aromatic ring, whereas ?CH3 eliminations were useful to identify the methyl and methoxy groups attached to this same ring. Nazarov cyclization in the gas phase occurred for all the investigated MKCs and did not depend on the presence of the hydroxyl group at the aromatic ring. However, the presence and the position of a hydroxyl group at the aromatic rings played a key role in the Nazarov cyclization mechanism. Conclusions: Our results reinforce some aspects of the fragmentation pathways previously published for 1,5-bis-(2-methoxyphenyl)-1,4-pentadien-3-one and 1,5-bis-(2-hydroxyphenyl)-1,4-pentadien-3-one. The alternative fragmentation mechanism proposed herein can explain the fragmentation of a wider diversity of monoketone curcuminoids.
- Vieira, Tatiana M.,Orenha, Renato P.,Crevelin, Eduardo J.,Furtado, Saulo S.P.,Vessecchi, Ricardo,Parreira, Renato L.T.,Crotti, Ant?nio E.M.
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- BENZOXAZINES WITH PHOTO-CURABLE LINKAGES, THERMOSETS THEREOF, AND PREPARATION OF THE SAME
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The subject invention provides benzoxazines with photo-curable linkages, thermosets thereof, and preparation methods of the same. The compounds of the subject invention can be used in manufacture of many kinds of cross-linking polymer material, and the obtained material is improved in terms of many properties, especially high thermal properties. Moreover, the preparation method of the subject invention can precisely synthesize the targeted products by simply steps.
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Page/Page column 11-12
(2021/01/12)
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- Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors
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EF24 is an IKKβ inhibitor (IC50: 72 μM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKβ were designed and synthesized. Several IKKβ inhibitors with better activities than EF24 were screened out and B3 showed best IKKβ inhibitory (IC50: 6.6 μM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKβ phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKKβ-NF-κB signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKKβ inhibitor as anti-tumor precursor.
- Jin, Rong,Chen, Qiuxiang,Yao, Song,Bai, Encheng,Fu, Weitao,Wang, Ledan,Wang, Jiabing,Du, Xiaojing,Wei, Tao,Xu, Haineng,Jiang, Chengxi,Qiu, Peihong,Wu, Jianzhang,Li, Wulan,Liang, Guang
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p. 218 - 228
(2018/01/26)
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- Design, in silico and in?vitro evaluation of curcumin analogues against Plasmodium falciparum
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The polyphenolic compound curcumin has been reported for its antimalarial properties in various scientific studies. Plasmodium falciparum ATP6, the parasite orthologue of mammalian sarcoplasmic Ca2+ ATPase (SERCA) has been identified as a key molecular target of both artemisinin and curcumin. The work was thereby undertaken to study the anti-malarial properties of two different series of curcumin analogues based on their docking interactions with PfATP6 and correlating the results with their anti-malarial activity. The compounds were designed retaining similar functional groups as that of the parent curcumin nucleus while incorporating changes in the carbon chain length, unsaturated groups and the number of ketone groups. The compounds (1E, 4E)-1,5-bis(4-methylphenyl)penta-1,4-dien-3-one (CD-9), (1E, 4E)-1,5-bis(4-methoxyphenyl)penta-1,4-dien-3-one (CD-8) and (E)-1,3-bis(4-hydroxylphenyl)prop-2-en-1-one (CD-1) showed IC50 values of 1.642?μM, 1.764?μM and 2.59?μM in 3D7 strain and 3.039?μM, 7.40?μM and 11.3?μM in RKL-2 strain respectively. Detailed structure-activity relationship studies of the compounds showed that CD-9 and CD-8 had a common hydrophobic interaction with the residue Leu268 of the PfATP6 protein and has been postulated through our study to be the reason for their antimalarial activity as seen after corroborating the results with the in?vitro study. The study provided valuable insight about the ligand-protein interaction of the various functional groups of curcumin and its analogues against the PfATP6 protein and their importance in imparting antimalarial action.
- Dohutia, Chandrajit,Chetia, Dipak,Gogoi, Kabita,Sarma, Kishore
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- Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.
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Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro. Most of these compounds showed good synergistic activities against C. tropicalis. Among them, compound 9 exhibited significant synergistic activities against Candida spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 μg ml-1 fluconazole and 64 μg ml-1 or 128 μg ml-1 compound 9 showed the most potent fungicidal effect against C. tropicalis. The synergistic effect may be associated with the changes of the intracellular ATP content and cell membrane permeability. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for fluconazole-resistant candidiasis.
- Zhao, Fei,Dong, Huai-Huai,Wang, Yuan-Hua,Wang, Tian-Yi,Yan, Ze-Hao,Yan, Fang,Zhang, Da-Zhi,Cao, Ying-Ying,Jin, Yong-Sheng
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p. 1093 - 1102
(2017/07/12)
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- TRPV-1 RECEPTOR ANTAGONIST COMPOUND DERIVED FROM 1,3,4-THIADIAZOLE ALKYLAMIDES AND CHALCONES
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This technology encompasses compounds derived from 1, 3, 4-thiadiazole alkylamides and chalcone, which inhibit the activation of the TRPV-1 receptor using capsaicin and temperature. Also disclosed is the use of these compounds in the treatment of diseases with TRPV-1 overexpression, such as chronic pain.
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Paragraph 0048
(2015/11/11)
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- Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway
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Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/β-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of β-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of β-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than 1a (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma.
- Leow, Pay-Chin,Bahety, Priti,Boon, Choon Pei,Lee, Chong Yew,Tan, Kheng Lin,Yang, Tianming,Ee, Pui-Lai Rachel
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- Bent shaped H-bonded mesogens derived from 1, 5-bis (4-hydroxyphenyl) penta-1, 4-dien-3-one: Synthesis, photophysical, mesomorphism and computational studies
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The synthesis, characterization, photophysical and mesomorphism of new hydrogen bonded (H-bonded) bent shaped mesogens derived from 1, 5-bis (4-hydroxyphenyl) penta-1, 4-dien-3-one are reported. The H-bonded bent shaped mesogens are formed by the complexation of 1: 2 molar ratio of 1, 5-bis (4-hydroxyphenyl) penta-1, 4-dien-3-one as bending unit and polar nitrile terminated ligands containing different linking groups (viz., imine (CHN), azo (NN), ester (COO)) as side wing. The transition temperatures and phase characterization have been investigated by differential scanning calorimetry and polarized optical microscopy. The bent core unit is fluorescent and non-mesogenic, whereas, all the nitrile terminated polar ligands are non-fluorescent and displayed enantiotropic smectic A phase. The H-bonded complexes are fluorescent and mesogenic. Nematic phase is induced in two H-bonded complexes whereas one of the H-bonded complexes displayed unidentified Bx phase. The computation studies are performed to obtain optimized stable molecular structures of the compounds, to investigate their electronic transitions and compared with experimental results.
- Paul, Manoj Kr.,Paul, Popita,Saha, Sandip Kumar,Choudhury, Sudip
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p. 226 - 235
(2014/06/24)
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- Mono-carbonyl curcumin analogues as 11β-hydroxysteroid dehydrogenase 1 inhibitors
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A series of structurally novel mono-carbonyl curcumin analogues have been synthesized and biologically evaluated to test their inhibitory potencies and the structure-activity relationship (SAR) on human and rat 11β- hydroxysteroid dehydrogenase isoform (11β-HSD1) activities. 11β-HSD1 selective inhibitors have been discovered and compound A10 is discovered as a very potent with an IC50 value of 97 nM without inhibiting 11β-HSD2.
- Lin, Han,Hu, Guo-Xin,Guo, Jingjing,Ge, Yufei,Liang, Guang,Lian, Qing-Quan,Chu, Yanhui,Yuan, Xiaohuan,Huang, Ping,Ge, Ren-Shan
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p. 4362 - 4366
(2013/07/25)
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- Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: Potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin
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A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin.
- Fang, Xubin,Fang, Lei,Gou, Shaohua,Cheng, Lin
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supporting information
p. 1297 - 1301
(2013/03/28)
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- Inhibitory effect of curcumin analogs on tissue factor procoagulant activity and their preliminary structure-activity relationships
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With the aim to explore the multifunctional behaviors of curcumin analogs and to discover new small molecular tissue factor inhibitors, twelve mono carbonyl curcumin analogs of three classes were synthesized and their effect on tissue factor procoagulant activity was evaluated in the human monoblastic leukemia THP-1 cells stimulated by LPS. The most potent compounds 2a exhibited the dramatically enhanced activity with the IC50 values of 0.053 nM. Their preliminary structure-activity relationship was also discussed.
- Ge, Hai-Xia,Chen, Ling,Zhang, Jian,Kou, Jun-Ping,Yu, Bo-Yang
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p. 3242 - 3246
(2013/07/27)
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- CURCUMIN ANALOGS AND METHODS OF USE THEREOF
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Curcumin analogs and methods of use thereof are provided.
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Page/Page column 20; 23
(2012/03/09)
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- Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors
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Anti-melanogenesis screening of 47 synthesized curcumin-like diarylpentanoid analogues was performed to show that some had a potent inhibitory effect on the melanogenesis in B16 melanoma cells. Their actions were considered to be mostly due to tyrosinase inhibition, tyrosinase expression inhibition, and melanin pigment degradation. The structure-activity relationships of those curcumin-like diarylpentanoid analogues which inhibited the melanogenesis and tyrosinase activity were also discussed. Of those compounds assayed, (2E,6E)-2,6-bis(2,5- dimethoxybenzylidene)cyclohexanone showed the most potent anti-melanogenesis effect, the mechanism of which is considered to be the degradation of the melanin pigment in B16 melanoma cells, affecting neither the tyrosinase activity nor tyrosinase expression. The Japanese Society of Pharmacognosy and Springer 2011.
- Hosoya, Takahiro,Nakata, Asami,Yamasaki, Fumie,Abas, Faridah,Shaari, Khozirah,Lajis, Nordin Hj,Morita, Hiroshi
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experimental part
p. 166 - 176
(2012/05/20)
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- Synthesis and evaluation of curcumin-related compounds for anticancer activity
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Sixty-one curcumin-related compounds were synthesized and evaluated for their anticancer activity toward cultured prostate cancer PC-3 cells, pancreas cancer Panc-1 cells and colon cancer HT-29 cells. Inhibitory effects of these compounds on the growth of PC-3, Panc-1 and HT-29 cells were determined by the MTT assay. Compounds E10, F10, FN1 and FN2 exhibited exceptionally potent inhibitory effects on the growth of cultured PC-3, Panc-1 and HT-29 cells. The IC50 for these compounds was lower than 1 μM in all three cell lines. E10 was 72-, 46- and 117-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. F10 was 69-, 34- and 72-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. FN1 and FN2 had about the same inhibitory effect as E10 and F10 toward Panc-1 cells but were less active than E10 and F10 toward PC-3 and HT-29 cells. The active compounds were potent stimulators of apoptosis. The present study indicates that E10, F10, FN1 and FN2 may have useful anticancer activity.
- Wei, Xingchuan,Du, Zhi-Yun,Zheng, Xi,Cui, Xiao-Xing,Conney, Allan H.,Zhang, Kun
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experimental part
p. 235 - 245
(2012/08/28)
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- Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes
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Objectives A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro. Methods The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol-based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique. Key findings Compounds 6, 17, 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7, 17, 18, 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration. Conclusions The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.
- Jantan, Ibrahim,Bukhari, Syed Nasir Abbas,Lajis, Nordin Haji,Abas, Faridah,Wai, Lam Kok,Jasamai, Malina
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experimental part
p. 404 - 412
(2012/07/02)
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- Synthesis and study of oxygen bridged liquid crystalline copolyesters
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Six new thermotropic liquid crystalline random copolyesters with ethereal linkages were prepared from mesogenic 4,4'-oxybis(benzoic acid) by direct polycondensation with different aromatic diols in pyridine solution. Diphenylchlorophosphate (DPCP) was employed as the condensation agent. The solution viscosity numbers ranged from 0.41-0.81 dL/g. The glass transition temperature of these polymers were determined by thermal studies (DSC and optical polarizing microscopy) and found to lie between 41.4 and 61.5 °C. Spectral studies (1H, 13C NMR and FT IR) gave an insight about the microstructure and copolymer compositions. The polyester composite film was exposed to UV irradiation to find changes in morphology by SEM analysis.
- Roopsingh,Malathy,Sathyamurthy,Kannappan
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experimental part
p. 81 - 84
(2011/11/28)
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- Photoactive liquid crystalline polyesters based on bisbenzylidene and pyridine moieties
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Photoactive main chain liquid crystalline polyesters containing bis(benzylidene)acetone and aromatic heterocyclic pyridine were synthesized by solution polycondensation. Chemical structure of monomers and polymers were confirmed by FT-IR, 1H and 13C NMR spectroscopy. Thermal property was investigated by TGA and DSC. Optical property of polyesters was studied in chloroform solution and in thin film under UV irradiation and exhibited cis-trans-photoisomerization. This behavior was witnessed by solubility, carbonyl group absorption band in FT-IR, optical microscopy as well as DSC analysis through existence of liquid crystallinity after irradiation of polymers.
- Deepa,Balamurugan,Kannan
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experimental part
p. 219 - 227
(2010/03/30)
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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, crystal structure and anti-inflammatory properties of curcumin analogues
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Curcuminoids have been reported to possess multifunctional bioactivities, especially the ability to inhibit proinflammatory induction. Since it has been suggested that the seven-carbon β-diketone linker in curcumin is responsible for its instability, nine mono-carbonyl five-carbon linker containing analogues were designed and synthesized. Their bioactivity against lipopolysaccharide-induced TNF-α amd IL-6 secretion was evaluated by using mouse J774.1 macrophages. The results showed that the 3′-methoxyl plays an important role in bioactivity and cyclohexanone containing analogues exhibited stronger inflammatory inhibition than acetone and cyclopentanone analogues. Subsequently the most active analogue 3c was determined using single-crystal X-ray diffraction. X-ray analysis and comparison with curcumin reveals that the presence of cyclohexanone in 3c, which remotely resembles the 6-membered ring in the enol tautomer in curcumin, may play an important role in the bioactivity. It is suggested that five-carbon linker analogues containing a cyclohexane ring which are synthetically assessable may be pharmacologically important.
- Liang, Guang,Yang, Shulin,Zhou, Huiping,Shao, Lili,Huang, Kexin,Xiao, Jian,Huang, Zhifeng,Li, Xiaokun
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experimental part
p. 915 - 919
(2009/09/08)
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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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- Synthesis and anti-bacterial properties of mono-carbonyl analogues of curcumin
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The synthesis of three series of curcumin analogues with mono-carbonyl is described. Their in vitro antibacterial activities against seven Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the aryl ring and the space structure of the linking strain were discussed. It was observed that part of the derivatives displayed significant activity when compared with curcumin and most of them exhibited activity against the ampicillin-resisted Enterobacter cloacae. Compounds A12, B09, B13, B14 and C09 show remarkable antibacterial activity in vitro. The result showed that heterocycle or long-chain substituents may enhance the activity of curcumin analogues.
- Liang, Guang,Yang, Shulin,Jiang, Lijuan,Zhao, Yu,Shao, Lili,Xiao, Jian,Ye, Faqing,Li, Yueru,Li, Xiaokun
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p. 162 - 167
(2008/09/19)
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- Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin
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Curcumin has been extensively studied for its anti-inflammatory activities. However, its potential beneficial effects on various disease preventions and treatments are limited by its unstable structure. The β-diketone moiety renders curcumin to be rapidly metabolized by aldo-keto reductase in liver. In the present study, a series of curcumin analogues with more stable chemical structures were synthesized and several compounds showed an enhanced ability to inhibit lipopolysaccharide (LPS)-induced TNF-α and IL-6 synthesis in macrophages.
- Liang, Guang,Li, Xiaokun,Chen, Li,Yang, Shulin,Wu, Xudong,Studer, Elaine,Gurley, Emily,Hylemon, Phillip B.,Ye, Faqing,Li, Yueru,Zhou, Huiping
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p. 1525 - 1529
(2008/09/19)
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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 2
(2008/06/13)
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- α-Glucosidase inhibition of natural curcuminoids and curcumin analogs
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Natural curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) isolated from Curcuma longa (turmeric), and synthetic curcumin analogs (A 1-7, B1-7, C1-6 and D1-7) were evaluated in vitro for the α-glucosidase inhibitory activity via UV and circular dichroism (CD) spectroscopy. The results indicated that natural curcuminoid compound 3 showed a remarkable inhibitory effect with IC 50 of 23.0 μM, and the synthetic compounds A2, B 2, C2 and D2 showed potent inhibitory effects with IC50 of 2.8, 2.6, 1.6 and 8.2 μM, respectively. Kinetic study exhibited that the mechanism of α-glucosidase inhibition of both 3 and C2 was non-competitive. The structure activity relationship revealed that the ortho dihydroxyl groups could form a more tight interaction with α-glucosidase to exert more potential inhibitory activities.
- Du, Zhi-Yun,Liu, Rong-Rong,Shao, Wei-Yan,Mao, Xue-Pu,Ma, Lin,Gu, Lian-Quan,Huang, Zhi-Shu,Chan, Albert S.C.
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p. 213 - 218
(2007/10/03)
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- Curcumin analogs as potent aldose reductase inhibitors
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In the present study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A2), 2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B2), 1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C2), and 3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D2) showed remarkably potent inhibitory effects on aldose reductase with IC50 of 2.9 μM, 2.6 μM, 3.4 μM, and 4.9 μM, respectively. The structure-activity relationship revealed that the curcumin analogs with ortho-dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities.
- Du, Zhi-Yun,Bao, Ya-Dan,Liu, Zhong,Qiao, Wei,Ma, Lin,Huang, Zhi-Shu,Gu, Lian-Quan,Chan, Albert S. C.
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p. 123 - 128
(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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- 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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- Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents
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A series of novel curcumin analogs were synthesized and screened for anti-cancer and anti-angiogenesis activities at Emory University and at the National Cancer Institute (NCI). These compounds are symmetrical α,β-unsaturated and saturated ketones. The majority of the analogs demonstrated a moderate degree of anti-cancer activity. Compounds 10, 11, and 14 exhibited a high degree of cytotoxicity in the NCI in vitro anti-cancer cell line screen. In addition, this screen revealed that these compounds inhibit tumor cell growth with a higher potency than the commonly used chemotherapeutic drug, cisplatin. In independent in vitro screens conducted at Emory, the same compounds plus 4, 5, 8, 9, and 13 exhibited a high degree of cytotoxicity to tumor cells. Analogs that were effective in the anti-cancer screens were also effective in in vitro anti-angiogenesis assays. Compounds 4, 9, 11, and 14 were most effective in the anti-angiogenesis assays run at Emory. In the assays conducted by the NCI, compound 14 was almost as potent as the anti-angiogenic drug TNP-470, which has undergone clinical trials. Based on the favorable in vitro anti-cancer and anti-angiogenesis results with 14, further in vivo tests were conducted. This compound effectively reduced the size of human breast tumors grown in female athymic nude mice and showed little toxicity. This data, coupled with the remarkable in vitro data, suggests that compound 14 may potentially be an effective chemotherapeutic agent. As a follow-up, a 3D quantitative structure relationship based on 14 has been developed. It shows a cross-validated r2(q2)=0.83 and a predictive r 2(p2)=0.71. COMPARE analysis suggests the compound to be a possible RNA/DNA antimetabolite, but also implies that the compound's cytotoxicity may arise from a presently unknown mechanism.
- Adams, Brian K.,Ferstl, Eva M.,Davis, Matthew C.,Herold, Marike,Kurtkaya, Serdar,Camalier, Richard F.,Hollingshead, Melinda G.,Kaur, Gurmeet,Sausville, Edward A.,Rickles, Frederick R.,Snyder, James P.,Liotta, Dennis C.,Shoji, Mamoru
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p. 3871 - 3883
(2007/10/03)
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- Curcumin analogs with anti-tumor and anti-angiogenic properties
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The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.
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- Geometrically and conformationally restrained cinnamoyl compounds as inhibitors of HIV-1 integrase: Synthesis, biological evaluation, and molecular modeling
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Various cinnammoyl-based structures were synthesized and tested in enzyme assays as inhibitors of the HIV-1 integrase (IN). The majority of compounds were designed as geometrically or conformationally constrained analogues of caffeic acid phenethyl ester (CAPE) and were characterized by a syn disposition of the carbonyl group with respect to the vinylic double bond. Since the cinnamoyl moiety present in flavones such as quercetin (inactive on HIV-1-infected cells) is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and conformational properties of the designed compounds were taken into account through analysis of X-ray structures available from the Cambridge Structural Database. The polyhydroxylated analogues were prepared by reacting 3,4-bis(tetrahydropyran- 2-yloxy)benzaldehyde with various compounds having active methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3-diacetylbenzene, 2,4- dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro-1,3-indandione, and others. While active against both 3'-processing and strand-transfer reactions, the new compounds, curcumin included, failed to inhibit the HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they specifically inhibited the enzymatic reactions associated with IN, being totally inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA polymerase II) nucleic acid-processing enzymes. On the other hand, title compounds were endowed with remarkable antiproliferative activity, whose potency correlated neither with the presence of catechols (possible source of reactive quinones) nor with inhibition of topoisomerases. The SARs developed for our compounds led to novel findings concerning the molecular determinants of IN inhibitory activity within the class of cinnamoyl-based structures. We hypothesize that these compounds bind to IN featuring the cinnamoyl residue C=C-C=O in a syn disposition, differently from flavone derivatives characterized by an anti arrangement about the same fragment. Certain inhibitors, lacking one of the two pharmacophoric catechol hydroxyls, retain moderate potency thanks to nonpharmacophoric fragments (i.e., a m-methoxy group in curcumin) which favorably interact with an 'accessory' region of IN. This region is supposed to be located adjacent to the binding site accommodating the pharmacophoric dihydroxycinnamoyl moiety. Disruption of coplanarity in the inhibitor structure abolishes activity owing to poor shape complementarity with the target or an exceedingly high strain energy of the coplanar conformation.
- Artico, Marino,Santo, Roberte Di,Costi, Roberta,Novellino, Ettore,Greco, Giovanni,Massa, Silvio,Tramontano, Enzo,Marongiu, Maria E.,De Montis, Antonella,Colla, Paolo La
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p. 3948 - 3960
(2007/10/03)
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- Antibacterials and antimycotics: Part 1: Synthesis and activity of 2- pyrazoline derivatives
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A series of 3-styryl-1,5-diphenyl and 5-styryl-1,3-diphenyl 2- pyrazolines of different substitutions has been synthesized by condensation of substituted α,β-unsaturated ketones with phenylhydrazine hydrochloride in presence of catalytic amount of concentrated HCl. Compounds in the 3- styryl series had OMe, NMe2, NO2, OH and isopropyl substituents and those in the 5-styryl series had OMe, NMe2 and NO(s). The 3-styryl-1,5-diphenyl compounds showed little variation in antibacterial activity towards gram- positive and gram-negative bacteria in terms of geometric mean minimum inhibitory concentrations (MIC). The 4',4-NMe2, 4',4-NO2 and 4',4-OMe compounds were found to possess the highest activity in the series. The 5- styryl-1,3-diphenyl series showed lower activities than the 3-styryl series. The in vitro antimycotic activity of the 4',4-OH and 2',2-OH substituted compounds showed good activity than the other molecules in the two series.
- Nauduri, Dhananjaya,Reddy, Gopu Bala Show
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p. 1254 - 1260
(2007/10/03)
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- 1,5-Diphenyl-1,4-pentadiene-3-ones and cyclic analogues as antioxidative agents. Synthesis and structure-activity relationship
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A series of 1,5-diphenyl-1,4-pentadiene-3-ones and cyclic analogues with OH-groups in the para position of the phenyl rings and various meta substituents were prepared and their antioxidant activity compared with that of curcumin. Most of them exhibited potent antioxidative activity, especially when all the meta positions were substituted by methoxy groups.
- Sardjiman,Reksohadiprodjo,Hakim,Van Der Goot,Timmerman
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p. 625 - 630
(2007/10/03)
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- Bisbenzoxazines and pharmaceutical use
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Compounds of the formula: STR1 wherein, R is H, alkyl, cycloalkyl, aryl, or heteroaryl; R1 is H, alkyl, cycloalkyl, aryl, heteroaryl, substituted heteroaryl, aralkyl, substituted aryl, halo, OR2, SR2, NR2, CF3, NO2, CN, COOR2, CHO, SO3 H or SO2 NH2, wherein R2 is H, methyl, ethyl or propyl; Y is STR2 Z is O, S, NH or CH2 ; X is --CH2 --, STR3 or --(CH2)n CHOH(CH2)n --; wherein R2 is H, methyl, ethyl or propyl; n is 1-10, and pharmaceutically acceptable salts thereof have antiallergy and antiinflammatory activity.
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