- Application of human PCID2 protein in preparation or screening of anti-tumor drugs and compound with anti-tumor activity
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The invention belongs to the technical field of biotechnology and gene therapy, and particularly relates to application of human PCID2 protein in preparation or screening of anti-tumor drugs and an anti-tumor compound. It is found that the PCID2 gene promotes tumor cell proliferation and regulates the cell cycle, is a key molecule for regulating tumor generation and development, and can be used as a target protein for preparing or screening anti-tumor drugs; meanwhile, human PCID2 protein is used as target protein, a class of PCID2 protein targeting antitumor compounds are screened out through a molecular docking technology, and the compounds can significantly inhibit tumor cell proliferation and promote tumor cell apoptosis.
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Paragraph 0094-0096; 0102-0103; 0123
(2021/06/02)
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- Novel chromenone derivatives having substituted biphenyl group and a pharmaceutical composition for prevention or treatment of allergic diseases compring the same
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The present invention relates to: a novel chromenone derivative compound capable of effectively suppressing an allergic immune response by inhibiting signal transduction mediated by thymic stromal lymphopoietin (TSLP); and a pharmaceutical composition capable of fundamentally preventing or treating various allergic diseases by using the same.COPYRIGHT KIPO 2021
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Paragraph 0076-0083; 0085-0089
(2020/11/26)
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- Melanogenic inhibition and toxicity assessment of flavokawain A and B on B16/F10 melanoma cells and zebrafish (Danio rerio)
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Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 μM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
- Abdul Bahari, Mohammad Nazri,Ahmad, Syahida,Akhtar, Muhammad Nadeem,Balia Yusof, Zetty Norhana,Latif, Naimah,Md Razip, Nurliyana Najwa,Mohd Ma’in, Farah Idayu,Sakeh, Nurshafika Mohd
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- Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation
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Inflammation is a complex biological response to stimuli. Activated macrophages induced excessively release of pro-inflammatory cytokines and mediators such as endogenous radical nitric oxide (NO) play a significant role in the progression of multiple inflammatory diseases. Both natural and synthetic chalcones possess a wide range of bioactivities. In this work, thirty-nine chalcones and three related compounds, including several novel ones, based on bioactive kava chalcones were designed, synthesized and their inhibitory effects on NO production in RAW 264.7 cells were evaluated. The novel compound (E)-1-(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (53) exhibited a better inhibitory activity (84.0%) on NO production at 10 μM (IC50 = 6.4 μM) with the lowest cytotoxicity (IC50 > 80 μM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress the progression of inflammation on collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models. In addition, the structure-activity relationship (SAR) of the kava chalcones based analogs was also depicted.
- Chen, Lijuan,Fan, Tiantian,Lei, Xiangui,Teichmann, Alexander Tobias,Wang, Amu,Wang, Chao,Wei, Zhe,Wieland, Frank Heinrich,Yang, Youzhe,Yin, Jinxiang,Zhou, Li,Zhu, Yue
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- Design, synthesis and biological evaluation of dimethyl cardamonin (DMC) derivatives as P-glycoprotein-mediated multidrug resistance reversal agents
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Background: P-glycoprotein (P-gp) has been regarded as an important factor in the multidrug resistance (MDR) of tumor cells within the last decade, which can be solved by inhibiting P-gp to reverse MDR. Thus, it is an effective strategy to develop inhibitor of P-gp. Objective: In this study, the synthesis of a series of derivatives had been carried out by bioisosterism design on the basis of Dimethyl Cardamonin (DMC). Subsequently, we evaluated their reversal activities as potential P-glycoprotein (P-gp)-mediated Multidrug Resistance (MDR) agents. Methods: Dimethyl cardamonin derivatives were synthesized from acetophenones and the corresponding benzaldehydes in the presence of 40% KOH by Claisen-Schmidt reaction. Their cytotoxicity and reversal activities in vitro were assessed with MTT. Moreover, the compound B4 was evaluated by Doxorubicin (DOX) accumulation, Western blot and wound-healing assays deeply. Results and Discussion: The results showed that compounds B2, B4 and B6 had the potency of MDR reversers with little intrinsic cytotoxicity. Meanwhile, these compounds also demonstrated the capability to inhibit MCF-7 and MCF-7/DOX cells migration. Besides, the most compound B4 was selected for further study, which promoted the accumulation of DOX in MCF-7/DOX cells and inhibited the expressionof P-gp at protein levels. Conclusion: The above findings may provide new insights for the research and development of P-gp-mediated MDR reversal agents.
- Liu, Jianwen,Ma, Lei,Shi, Ximeng,Yin, Huanhuan,Zhao, Yuyu,Zhou, Licheng
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p. 1270 - 1282
(2020/10/06)
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- Total synthesis of wikstrol A and wikstrol B
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The first total synthesis of wikstrol A and wikstrol B was achieved by employing aldol reaction, Sharpless asymmetric dihydroxylation, regioselective iodination, Sonogashira coupling, and rhodium-catalyzed oxidative coupling as key steps. The structure of the key intermediate for wikstrol A was confirmed via its derivative by single-crystal X-ray analysis.
- Lu, Kui,Li, Ming,Huang, Yuna,Sun, Yuanyuan,Gong, Zhi,Wei, Qijun,Zhao, Xia,Zhang, Yongmin,Yu, Peng
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p. 8206 - 8213
(2019/09/19)
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- Targeting the MDM2-p53 protein-protein interaction with prenylchalcones: Synthesis of a small library and evaluation of potential antitumor activity
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Prenylation of several bioactive scaffolds is a very interesting strategy used in Medicinal Chemistry in order to improve biological/pharmacological effects. A small library of prenylchalcones was synthesized and evaluated for the ability to inhibit the MDM2-p53 interaction using a yeast-based assay. The capacity of all synthesized prenylchalcones and their non-prenylated precursors to inhibit the growth of human colon tumor HCT116 cells was also evaluated. The obtained results led to the identification of a hit compound, prenylchalcone 2e, which behaved as potential inhibitor of the MDM2-p53 interaction in yeast, and showed improved cytotoxicity against human tumor cells expressing wild-type p53, including liver hepatocellular carcinoma HepG2, breast adenocarcinoma MCF-7, and malignant melanoma A375 cells. In colon cancer cells, it was also shown that the growth inhibitory effect of prenylchalcone 2e was associated with the induction of cell cycle arrest, apoptosis, and increased protein expression levels of p53 transcriptional targets. Moreover, computational docking studies were performed in order to predict docking poses and residues involved in the MDM2-p53 potential interaction.
- Brand?o, Pedro,Loureiro, Joana B.,Carvalho, Sylvie,Hamadou, Meriem Hadjer,Cravo, Sara,Moreira, Joana,Pereira, Daniela,Palmeira, Andreia,Pinto, Madalena,Saraiva, Lucília,Cidade, Honorina
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p. 711 - 721
(2018/07/29)
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- Synthesis of Benzopyran-Fused Flavone Derivatives via Microwave-Assisted Intramolecular C-H Activation
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A microwave-assisted intramolecular direct arylation method for the synthesis of benzopyran-fused flavone derivatives containing natural flavone backbones is described. Different polyalkoxy flavones were synthesized and functionalized with 2-bromobenzyl bromide. The resulting compounds were subjected to palladium-catalyzed intramolecular direct arylation reactions supported by microwave irradiation to produce fused tetracyclic flavones. In the case of the 7-substituted chrysin derivative, the regioselectivity of the coupling was also examined.
- Sipos, Zoltán,Kónya, Krisztina
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p. 1610 - 1620
(2018/03/21)
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- Design, synthesis and docking studies of flavokawain B type chalcones and their cytotoxic effects on MCF-7 and MDA-MB-231 cell lines
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Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure-activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by 1H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques.
- Bakar, Addila Abu,Akhtar, Muhammad Nadeem,Ali, Norlaily Mohd,Yeap, Swee Keong,Quah, Ching Kheng,Loh, Wan-Sin,Alitheen, Noorjahan Banu,Zareen, Seema,Ul-Haq, Zaheer,Shah, Syed Adnan Ali
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- Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives
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22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study to understand the structural requirements for optimum and selective cytotoxicity. FKd and natural flavokawains A and B found into kava, a South Pacific traditional beverage, were evaluated against nine cancer and one healthy cell lines. The targeted cell cycle phases as well as the effects on the induction of apoptosis and cell cycle protein levels were investigated. Therapeutic improvements (more activity and selectivity) were achieved with FKd compared to natural flavokawains and notably with the 2′,3,4′,6′-tetramethoxychalcone (FKd 19). FKd induced a G1/S arrest on p53 wild-type cells and an M arrest on p53 mutant-type, via the up-regulation of p21 and cyclin B1 proteins, followed by apoptosis. Moreover, FKd exhibited a 24?h-effect on Akt/mTor normal cells versus a 48?h-effect on Akt/mTor up-regulated cells. The SAR study resulted in the conclusion that trimethoxy A-ring allowed the best compromise between cytotoxicity and selectivity, as well as the substitution of the meta position on the B-ring and the use of halogens substituents.
- Thieury, Charlotte,Lebouvier, Nicolas,Le Guével, Rémy,Barguil, Yann,Herbette, Ga?tan,Antheaume, Cyril,Hnawia, Edouard,Asakawa, Yoshinori,Nour, Mohammed,Guillaudeux, Thierry
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p. 1817 - 1829
(2017/03/08)
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- Synthesis of 5-subsituted flavonols via the Algar-Flynn-Oyamada (AFO) reaction: The mechanistic implication
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Herein, we report a synthetic method with improved selectivity for 5-substituted flavonols via the Algar-Flynn-Oyamada reaction (AFO), by using of sodium carbonate/hydrogen peroxide A series of 5-substituted flavonols was obtained with moderate to high yields. The mechanism of the AFO reaction was elucidated. LCMS analysis and in situ 1H NMR analysis indicated that the epoxide was involved in the transformation from chalcone to flavonol and/or aurone under alkaline base/peroxide conditions.
- Shen, Xianyan,Zhou, Qiang,Xiong, Wei,Pu, Wenchen,Zhang, Wei,Zhang, Guolin,Wang, Chun
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p. 4822 - 4829
(2017/07/17)
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- New developments in the synthesis of (e)-8-styrylflavones
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A novel route for the synthesis of new (E)-8-styrylflavones is reported. This methodology involves the regio- and stereoselective Heck cross-coupling reaction of 8-iodoflavones and styrene derivatives. The Heck precursors, 8-iodoflavones, were obtained through an efficient regioselective one-pot oxidative cyclization-iodination reaction of (E)-2′-hydroxychalcones by applying the iodine/dimethyl sulfoxide system.
- De Azevedo, Orlando D. C. C.,Seixas, Raquel S. G. R.,Silva, Artur M. S.
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p. 1379 - 1384
(2015/06/16)
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- Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship
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Browning of fruits and vegetables is a serious issue in the food industry, as it damages the organoleptic properties of the final products. Overproduction of melanin causes aesthetic problems such as melisma, freckles and lentigo. In this study, a series of chalcones (1-10) have been synthesized and examined for their tryrosinase inhibitory activity. The results showed that flavokawain B (1), flavokawain A (2) and compound 3 were found to be potential tyrosinase inhibitors, indicating IC50 14.20-14.38 μM values. This demonstrates that 4-substituted phenolic compound especially at ring A exhibited significant tyrosinase inhibition. Additionally, molecular docking results showed a strong binding affinity for compounds 1-3 through chelation between copper metal and ligands. The detailed molecular docking and SARs studies correlate well with the tyrosinase inhibition studies in vitro. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and single X-ray crystallographic techniques. These findings could lead to design and discover of new tyrosinase inhibitors to control the melanine overproduction and overcome the economic loss of food industry.
- Akhtar, Muhammad Nadeem,Sakeh, Nurshafika M.,Zareen, Seema,Gul, Sana,Lo, Kong Mun,Ul-Haq, Zaheer,Shah, Syed Adnan Ali,Ahmad, Syahida
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- Chalcones with electron-withdrawing and electron-donating substituents: Anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins
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In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.
- Mai, Chun Wai,Yaeghoobi, Marzieh,Abd-Rahman, Noorsaadah,Kang, Yew Beng,Pichika, Mallikarjuna Rao
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supporting information
p. 378 - 387
(2014/04/17)
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- Flavokawain a induces apoptosis in MCF-7 and MDA-MB231 and inhibits the metastatic process in vitro
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Introduction: The kava-kava plant (Piper methsyticum) is traditionally known as the pacific elixir by the pacific islanders for its role in a wide range of biological activities. The extract of the roots of this plant contains a variety of interesting mol
- Abu, Nadiah,Akhtar, M. Nadeem,Yeap, Swee Keong,Lim, Kian Lam,Ho, Wan Yong,Zulfadli, Aimi Jamil,Omar, Abdul Rahman,Sulaiman, Mohd Roslan,Abdullah, Mohd Puad,Alitheen, Noorjahan Banu
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- Synthesis and biological evaluation of flavones and benzoflavones as inhibitors of BCRP/ABCG2
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Multidrug resistance (MDR) often leads to a failure of cancer chemotherapy. Breast Cancer Resistance Protein (BCRP/ABCG2), a member of the superfamily of ATP binding cassette proteins has been found to confer MDR in cancer cells by transporting molecules with amphiphilic character out of the cells using energy from ATP hydrolysis. Inhibiting BCRP can be a solution to overcome MDR.We synthesized a series of flavones, 7,8-benzofl avones and 5,6-benzo flavones with varying substituents at positions 3, 3′ and 4′ of the (benzo)fl avone structure. All synthesized compounds were tested for BCRP inhibition in Hoechst 33342 and pheophorbide A accumulation assays using MDCK cells expressing BCRP. All the compounds were further screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity by calcein AM accumulation assay to check the selectivity towards BCRP. In addition most active compounds were investigated for their cytotoxicity. It was observed that in most cases 7,8-benzoflavones are more potent in comparison to the 5,6-benzoflavones. In general it was found that presence of a 3-OCH3 substituent leads to increase in activity in comparison to presence of OH or no substitution at position 3. Also, it was found that presence of 3′,4′-OCH3 on phenyl ring lead to increase in activity as compared to other substituents. Compound 24, a 7,8-benzoflavone derivative was found to be most potent being 50 times selective for BCRP and showing very low cytotoxicity at higher concentrations.
- Juvale, Kapil,Stefan, Katja,Wiese, Michael
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p. 115 - 126
(2013/10/01)
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- Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein
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Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the current study was to investigate different multi-substituted chalcones for their BCRP inhibition. We synthesized chalcones and benzochalcones with different substituents (viz. OH, OCH3, Cl) on ring A and B of the chalcone structure. All synthesized compounds were tested by Hoechst 33342 accumulation assay to determine inhibitory activity in MCF-7 MX and MDCK cells expressing BCRP. The compounds were also screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity in the calcein AM accumulation assay and were found to be selective towards inhibition of BCRP. Substituents at position 2′ and 4′ on chalcone ring A were found to be essential for activity; additionally there was a great influence of substituents on ring B. Presence of 3,4-dimethoxy substitution on ring B was found to be optimal, while presence of 2- and 4-chloro substitution also showed a positive effect on BCRP inhibition.
- Juvale, Kapil,Pape, Veronika F.S.,Wiese, Michael
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experimental part
p. 346 - 355
(2012/03/09)
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- COMPOUNDS, THEIR SYNTHESES, AND THEIR USES
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Embodiments of the present invention provide compounds (such as Formula (I) compounds, Formula (II) compounds, and various embodiments thereof). Compositions comprising those compounds are also provided. Methods for their preparation are included. Also, uses of the compounds are included, such as administering and treating diseases (e.g., cancer and infections).
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- Natural and synthetic 2′-hydroxy-chalcones and aurones: Synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity
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A series of 2′-hydroxy-chalcones and their oxidative cyclization products, aurones, have been synthesized and tested for their antioxidant and lipoxygenase inhibitory activity. The natural product aureusidin (31) was synthesized in high yield by a new approach. An extensive structure-relationship study was performed and revealed that several chalcones and aurones possess an appealing pharmacological profile combining high antioxidant and lipid peroxidation activity with potent soybean LOX inhibition.
- Detsi, Anastasia,Majdalani, Maya,Kontogiorgis, Christos A.,Hadjipavlou-Litina, Dimitra,Kefalas, Panagiotis
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experimental part
p. 8073 - 8085
(2010/03/24)
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- Synthesis, cytotoxicity, and anti-Trypanosoma cruzi activity of new chalcones
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Synthesis of a cytotoxic dihydrochalcone, first isolated from a traditional Amazonian medicinal plant Iryanthera juruensis Warb (Myristicaceae), followed by a comprehensive SAR analysis of saturated and unsaturated chalcone synthetic intermediates, led to the identification of analogues with selective and significant in vitro anti-Trypanosoma cruzi activity. Further SAR studies were undertaken with the synthesis of 21 new chalcones containing two allyloxy moieties that resulted in the discovery of 2′,4′-diallyloxy- 6′-methoxy chalcones with improved selectivity against this parasite at concentrations below 25 μM, four of which exhibited a selectivity index greater than 12.
- Aponte, José C.,Verástegui, Manuela,Málaga, Edith,Zimic, Mirko,Quiliano, Miguel,Vaisberg, Abraham J.,Gilman, Robert H.,Hammond, Gerald B.
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experimental part
p. 6230 - 6234
(2009/09/25)
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- Structural basis for the activity of the RSK-specific inhibitor, SL0101
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Inappropriate activity of p90 ribosomal S6 kinase (RSK) has been implicated in various human cancers as well as other pathologies. We previously reported the isolation, characterization, and synthesis of the natural product kaempferol 3-O-(3″,4″-di-O-acetyl-α-l-rhamnopyranoside), termed SL0101 [Smith, J. A.; Poteet-Smith, C. E.; Xu, Y.; Errington, T. M.; Hecht, S. M.; Lannigan, D. A. Cancer Res., 2005, 65, 1027-1034: Xu, Y.-M; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Bioorg. Med. Chem., 2006, 14, 3974-3977: Maloney, D. J.; Hecht, S. M. Org. Lett., 2005, 7, 1097-1099]. SL0101 is a potent and specific inhibitor of RSK; therefore, we performed an analysis of the structural basis for the inhibitory activity of this lead compound. In in vitro kinase assays we found that acylation of the rhamnose moiety and the 4′, 5, and 7-hydroxyl groups are responsible for maintaining a high affinity interaction of RSK with SL0101. It is likely that the hydroxyl groups facilitate RSK binding through their ability to form hydrogen bonds. To determine whether the SL0101 derivatives were specific for inhibition of RSK we analyzed their ability to preferentially inhibit the growth of the human breast cancer line, MCF-7, compared to the normal human breast line, MCF-10A. We have previously validated this differential growth assay as a convenient readout for analyzing the specificity of RSK inhibitors [Smith, J. A.; Maloney, D. J.; Clark, D. E.; Xu, Y.-M.; Hecht, S. M.; Lannigan, D. A. Bioorg. Med. Chem., 2006, 14, 6034-6042]. We found that acylation of the rhamnose moiety was essential for maintaining the selectivity for RSK inhibition in intact cells. Further, the efficacy of SL0101 in intact cells is limited by cellular uptake as well as possible hydrolysis of the acetyl groups on the rhamnose moiety by ubiquitous intracellular esterases. These studies should facilitate the development of a RSK inhibitor, based on the SL0101 pharmacophore, as an anti-cancer chemotherapeutic agent.
- Smith, Jeffrey A.,Maloney, David J.,Hecht, Sidney M.,Lannigan, Deborah A.
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p. 5018 - 5034
(2008/03/12)
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- Synthetic chalcones, flavanones, and flavones as antitumoral agents: Biological evaluation and structure-activity relationships
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A series of synthetic chalcones, flavanones, and flavones has been synthesized and evaluated for antitumor activity against the human kidney carcinoma cells TK-10, human mammary adenocarcinoma cells MCF-7 (estrogen receptor-positive), and human colon adenocarcinoma cells HT-29. The most active series is the chalcone ones with the best results against TK-10 and HT-29 cells. Fourteen out of 53 analyzed compounds resulted very active against at least two of the studied tumoral cells. Alkaline single cell gel electrophoresis, comet assay, was performed as a study of the chromosomal aberrations promoted by the compounds on normal cells. Four active and two inactive chalcones were studied in the comet assay against normal human kidney cells (HK-2). A structure-activity relationship analysis of these compounds was performed and for 4- and 3,4-disubstituted derivatives a quantitative correlation was obtained in the case of anti-HT-29 activity.
- Cabrera, Mauricio,Simoens, Macarena,Falchi, Gabriela,Lavaggi, M. Laura,Piro, Oscar E.,Castellano, Eduardo E.,Vidal, Anabel,Azqueta, Amaia,Monge, Antonio,de Cerain, Adela Lopez,Sagrera, Gabriel,Seoane, Gustavo,Cerecetto, Hugo,Gonzalez, Mercedes
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p. 3356 - 3367
(2008/02/07)
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- Synthesis of isoflavones containing naturally occurring substitution pattern by oxidative rearrangement of respective flavanones using thallium(III) p-tosylate
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Claisen condensation of substituted 2′-hydroxyacetophenones 1a-c with aromatic aldehydes affords respective substituted 2′-hydroxychalcones 2a-n which on base catalyzed cyclization in pyridine:methanol:water (1:1:1) give respective flavanones 3a-n. The oxidative rearrangement of flavanones with thallium(III) p-tosylate furnishes respective isoflavones 4a-n in overall 62-72% yields starting from 1. The present methodology has been successfully applied for the synthesis of naturally occurring isoflavones such as di-O-methyldaidzein 4a, cabruvin 4b, pseudobabtigenin methylether 4d, 5,7-dimethoxyisoflavone 4f, 5,7,4′-trimethoxyisoflavone 4g, derrustone 4i, 7,8,3′,4′- tetramethoxyisoflavone 41, purpuranin-A 4m and 7,8,3′,4′,5′- pentamethoxyisoflavone 4n and thus the first synthesis of 4n is reported.
- Singh, Om V.,Muthukrishnan,Sunderavadivelu
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p. 2575 - 2581
(2007/10/03)
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- Total synthesis of kaempferol and methylated kaempferol derivatives
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Kaempferol (1), a natural product from various plants, was synthesized in which the longest linear sequence is only seven steps in overall yields of 47% from commercially available 1,3,5-trimethoxybenzene (10). The methylated kaempferols 2-5 were also prepared by use of this concise synthetic methodology. The key transformations in this synthesis involved the I2 oxidative-promoting-cyclization and DDO oxidative hydroxylation. Several strategies to achieve 1 are provided.
- Lee, Yean-Jang,Wu, Tsao-Dong
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p. 201 - 206
(2007/10/03)
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- Insect antifeedant flavonoids from Gnaphalium affine D. Don
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The antifeedant flavonoids, 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (1), 5-hydroxy-3,6,7,8-tetramethoxyflavone (2), 5,6-dihydroxy-3,7- dimethoxyflavone (3), and 4,4',6'-trihydroxy-2'-methoxychalcone (4), have been isolated from cudweed Gnaphalium affine D. Don (Compositae). Four natural flavonoids showed insect antifeedant activity against the common cutworm (Spodoptera litura F.). These flavonoids were detected in small amounts in the plant by HPLC analysis, but these natural compounds had strong antifeedant activity against the common cutworm. On the other hand, 4 was detected in a large amount in the plant, but this compound had only a slight activity. Therefore, these natural compounds were regarded as one of the plant's defensive systems against phytophagous insects along with the woolly plant surface. As for the structure-activity relationship, it is an advantage for antifeedant activity to have no oxy-substituents on the B-ring of the flavonoid but have an ether linkage such as a pyran in the chemical structure.
- Morimoto, Masanori,Kumeda, Sumiko,Komai, Koichiro
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p. 1888 - 1891
(2007/10/03)
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- Anti-ulcer agent comprising chalcone derivative as effective ingredient and novel chalcone derivative
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The present invention relates to an anti-ulcer agent comprising a compound represented by the following general formula I as the effective ingredient, and a novel chalcone derivative included in the compound represented by this general formula I: STR1 wherein X and Y independently stand for a hydrogen atom or together form a single bond, R1 stands for a hydroxyl group, an acetoxy group, a carboxymethoxy group or a methoxycarbonylmethoxy group, R2 stands for a hydrogen atom, an isoprenyl group, isopentyl group or a propyl group, R3 stands for hydroxyl group or a methoxy group, R4 stands for a hydrogen atom, a hydroxyl group or a methoxy group, R5 stands for a hydrogen atom, a hydroxyl group, a methoxy group or an isopentyl group, R6 stands for a hydroxyl group, a methoxy group or a carboxymethoxy group, and R7 stands for a hydrogen atom or a methoxy group.
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- 13C Nuclear Magnetic Resonance Studies on 1,3-Diphenylprop-2-enones
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The 13C NMR spectra of 48 differently substituted chalcones (1,3-diphenylprop-2-enones) have been recorded and the results are discussed.The data will be useful in the identification of new/natural chalcones.
- Parmar, V. S.,Sharma, Sunil,Rathore, J. S.,Garg, Meenu,Gupta, Sandhya,et al.
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p. 470 - 474
(2007/10/02)
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- Synthesis of a New Flavone
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The structure of the naturally occuring flavone 5-O-methylacacetin (I) has been confirmed by its synthesis. 5,7-Di-O-methylacacetin has been synthesised.
- Srivastava, Savitri D.,Srivastava, Santosh K.
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- Substituted acetophenones and compositions containing them
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Antivirally active compounds of the formula STR1 wherein R1 represents hydroxy, acyloxy derived from an aliphatic acid having 2-18 carbon atoms or a heterocyclic carboxylic acid containing nitrogen atom(s), lower alkoxycarbonyloxy, aminoacyloxy or carboxyalkanoyloxy; R2 represents lower alkoxy; R3 represents hydrogen or lower alkoxy; and R4 represents phenyl which may be substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, benzyloxy, allyloxy, alkylthio, dialkylamino, amino, cyano, hydroxy, halo and alkylenedioxy; or pyridyl, furyl, thienyl or pyrrolyl which may be substituted by lower alkyl, pharmaceutical compositions containing them and a process for the preparation of those compounds of formula I which are novel.
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