2198-19-8Relevant articles and documents
Crystal-packing modes determine the solid-state ESIPT fluorescence in highly dipolar 2′-hydroxychalcones
Bordy, Mathieu,Bretonnière, Yann,Hasserodt, Jens,Jeanneau, Erwann,Tordo, Alix
supporting information, p. 12727 - 12731 (2021/10/06)
This work describes the systematic study of the structure-luminescence relationship of 15 hydroxy-chalcones directly in the crystal state. Chalcones are easily assembled at the gram scale allowing for efficient variation of their substitution motifs. Our molecule variants combine two modes of fluorescence generation, ESIPT and ICT, both known for their potential to achieve significant quantum yields even with emission in the red to near infrared, a region preferred for technologies as diverse as optoelectronics and chemical sensing. Quantum yields as high as 48% (at 665 nm) and emission wavelengths in the deep red region (710 nm, 5%) were achieved with variants equipped with a strained amino substituent in the donor portion (azetidinyl). Systematic XRD analysis of large monocrystals allowed for the identification of the subtle interplay of several inter- and intra-molecular parameters in achieving such performances, be it intramolecular planarity, non-classical H-bonds, and stacking modes.
Natural and Semisynthetic Chalcones as Dual FLT3 and Microtubule Polymerization Inhibitors
Malik, Haleema Sadia,Bilal, Aishah,Ullah, Rahim,Iqbal, Maheen,Khan, Sardraz,Ahmed, Ishtiaq,Krohn, Karsten,Saleem, Rahman Shah Zaib,Hussain, Hidayat,Faisal, Amir
, p. 3111 - 3121 (2020/11/02)
Activating mutations in FLT3 receptor tyrosine kinase are found in a third of acute myeloid leukemia (AML) patients and are associated with disease relapse and a poor prognosis. The majority of these mutations are internal tandem duplications (ITDs) in the juxtamembrane domain of FLT3, which have been validated as a therapeutic target. The clinical success of selective inhibitors targeting oncogenic FLT3, however, has been limited due to the acquisition of drug resistance. Herein the identification of a dual FLT3/microtubule polymerization inhibitor, chalcone 4 (2′-allyloxy-4,4′-dimethoxychalcone), is reported through screening of 15 related chalcones for differential antiproliferative activity in leukemia cell lines dependent on FLT3-ITD (MV-4-11) or BCR-ABL (K562) oncogenes and by subsequent screening for mitotic inducers in the HCT116 cell line. Three natural chalcones (1-3) were found to be differentially more potent toward the MV-4-11 (FLT3-ITD) cell line compared to the K562 (BCR-ABL) cell line. Notably, the new semisynthetic chalcone 4, which is a 2′-O-allyl analogue of the natural chalcone 3, was found to be more potent toward the FLT3-ITD+ cell line and inhibited FLT3 signaling in FLT3-dependent cells. An in vitro kinase assay confirmed that chalcone 4 directly inhibited FLT3. Moreover, chalcone 4 induced mitotic arrest in these cells and inhibited tubulin polymerization in both cellular and biochemical assays. Treatment of MV-4-11 cells with this inhibitor for 24 and 48 h resulted in apoptotic cell death. Finally, chalcone 4 was able to overcome TKD mutation-mediated acquired resistance to FLT3 inhibitors in a MOLM-13 cell line expressing FLT3-ITD with the D835Y mutation. Chalcone 4 is, therefore, a promising lead for the discovery of dual-target FLT3 inhibitors.
Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation
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
supporting information, (2020/03/24)
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.
Crystal structures, Hirshfeld surface analysis and PIXEL calculations of four (E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one derivatives, containing methoxy substituents. The importance of π interactions
Gomes, Ligia R.,Low, John N.,Pinheiro, Alessandra C.,Turner, Alan B.,Wardell, James L.
, (2020/07/08)
A detailed structural analysis has been carried out on four chalcone (E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one derivatives, having a varying number of methoxy substituents, namely (E)-3-(3,4-dimethoxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one, (1),
NOTCH INHIBITORS FOR USE IN THE TREATMENT OF T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
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Page/Page column 25; 27, (2018/07/29)
Compounds of formula (I) in the capacity of compounds with anti-tumor activity for the treatment of T-cell acute lymphoblastic leukemia (T-ALL).
Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents
Vijaya Bhaskar Reddy, Mopur,Hung, Hsin-Yi,Kuo, Ping-Chung,Huang, Guan-Jhong,Chan, Yu-Yi,Huang, Shiow-Chyn,Wu, Shwu-Jen,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung,Wu, Tian-Shung
supporting information, p. 1547 - 1550 (2017/03/17)
Twenty-one chalcones were prepared via aldol condensation and subsequent reduction of these compound led to the corresponding dihydrochalcone and 1,3-diphenylpropane derivatives. The synthetic products were examined for their effects on NO inhibition in L
Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds
Borsari, Chiara,Santarem, Nuno,Torrado, Juan,Olías, Ana Isabel,Corral, María Jesús,Baptista, Catarina,Gul, Sheraz,Wolf, Markus,Kuzikov, Maria,Ellinger, Bernhard,Witt, Gesa,Gribbon, Philip,Reinshagen, Jeanette,Linciano, Pasquale,Tait, Annalisa,Costantino, Luca,Freitas-Junior, Lucio H.,Moraes, Carolina B.,Bruno dos Santos, Pascoalino,Alcantara, Laura Maria,Franco, Caio Haddad,Bertolacini, Claudia Danielli,Fontana, Vanessa,Tejera Nevado, Paloma,Clos, Joachim,Alunda, José María,Cordeiro-da-Silva, Anabela,Ferrari, Stefania,Costi, Maria Paola
supporting information, p. 1129 - 1135 (2017/01/12)
Chalcones display a broad spectrum of pharmacological activities. Herein, a series of 2’-hydroxy methoxylated chalcones was synthesized and evaluated towards Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Among the synthesized library, com
Synthesis of 5-subsituted flavonols via the Algar-Flynn-Oyamada (AFO) reaction: The mechanistic implication
Shen, Xianyan,Zhou, Qiang,Xiong, Wei,Pu, Wenchen,Zhang, Wei,Zhang, Guolin,Wang, Chun
, p. 4822 - 4829 (2017/07/17)
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.
Certain 4-iminoflavones derivatives: Synthesis, docking studies, antiasthmatic and antimicrobial agents
Khah, Shaila,Goyal, Rohit,Chabba, Ankush,Jaiswal, Varun,Sharma, Gaurav,Naushad
, p. 1687 - 1696 (2016/07/06)
In this present study, certain substituted 4-iminoflavone derivatives 5(a-j) were synthesized. All the synthesized compounds were evaluated for antiasthmatic and antimicrobial activity. Among the synthesized compounds, 5f was found to be the most promising against asthmatic models, whilst, 5h was found active against all the microbial strains. Antiasthmatic activity was correlated and evaluated with various models, e.g., citric acid induced cough model, OVA induced asthma model (biochemical estimation for cell infiltrations, estimation of lipid peroxidation and glutathione and estimation of TNF-α and IL-6 and histamine induced response). Compound 5f was found to show 2.20 ± 0.047 number of cough whilst codeine showed 1.40 ± 0.548; compound 5f produced considerable reduction in neutrophils, lymphocytes, eosinophils and leukocytes; decrease in LPO level (lung and BALF) and increment in GSH level (lungand BALF); and decreased the level of TNF-α and IL-6, respectively. On the other hand, 5h showed MIC 6.25 μg/mL against B. subtilis and S. aureus, 3.1 μg/mL against E. coli, 1.55 μg/mL against S. typhi and 6.25 μg/mL against C. albicans, respectively. In addition to gain better understanding on the biological activities of synthesized compounds, molecular docking study was performed within the binding site of human histamine H1 receptor and Glc-6-P synthase revealing compound 5f and 5h as best fit within the respective receptor pockets.
Profiling of flavonol derivatives for the development of antitrypanosomatidic drugs
Borsari, Chiara,Lucian, Rosaria,Pozzi, Cecilia,Poehner, Ina,Henrich, Stefan,Trande, Matteo,Cordeiro-Da-silva, Anabela,Santarem, Nuno,Baptista, Catarina,Tait, Annalisa,Di Pisa, Flavio,Iacono, Lucia Dello,Landi, Giacomo,Gul, Sheraz,Wolf, Markus,Kuzikov, Maria,Ellinger, Bernhard,Reinshagen, Jeanette,Witt, Gesa,Gribbon, Philip,Kohler, Manfred,Keminer, Oliver,Behrens, Birte,Costantino, Luca,Nevado, Paloma Tejera,Bifeld, Eugenia,Eick, Julia,Clos, Joachim,Torrado, Juan,Jiménez-Antón, María D.,Corral, María J.,Alunda, José Ma,Pellati, Federica,Wade, Rebecca C.,Ferrari, Stefania,Mangani, Stefano,Costi, Maria Paola
, p. 7598 - 7616 (2016/09/04)
Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 μM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies. Encapsulation of compound 2 in PLGA nanoparticles or cyclodextrins resulted in lower in vitro toxicity when compared to the free compound. Combination studies with methotrexate revealed that compound 13 (3-hydroxy-6-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one) has the highest synergistic effect at concentration of 1.3 μM, 11.7-fold dose reduction index and no toxicity toward host cells. Our results provide the basis for further chemical modifications aimed at identifying novel antitrypanosomatidic agents showing higher potency toward PTR1 and increased metabolic stability.
