- Design, synthesis of novel pyrazolopyridine derivatives and CREBBP bromodomain inhibitors docking and molecular dynamics
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A sequence of novel compounds pyrazolopyridine have been prepared by a general synthetic method. Due to high efficiency and selectivity, anticancer agents consisting of combined molecules have gained great interests. The IC50 values have been determined against cell line U937, the results obtained indicate the potential effects against cancer cell line. The cell potency of cell line is best for compounds 4a IC50 = 62.5 μM, 5b IC50 = 62.5 μM,4b IC50 = 31.2 μM, 4e IC50 = 31.2 μM), selectivity and in vivo. Further, the molecular docking studies indicate that substituted pyrazolo[4,3-c]pyridine derivatives show good anticancer activity in the medicinal field. The ease of synthesis and the significant biological activities make these compounds potential new frameworks for progress of cancer therapeutics. Compound 4f shows anticancer effect in cancer cell lines and in vivo that corresponds with antitumor activity in an AML cancer type. For the molecular docking with the ligands, the RMSD value has been calculated, the protein with the least RMSD is found to be 5KTU screening with 20 small molecules.
- Aruna, S.,Girija, R.,Saamanthi, M.,Vinod, D.
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p. 746 - 754
(2021/09/28)
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- Structure activity relationship analysis of antiproliferative cyclic C5-curcuminoids without DNA binding: Design, synthesis, lipophilicity and biological activity
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The chemical susceptibility of the β-diketone linker between the two aromatic rings in the structure of curcumin to hydrolysis and metabolism has made it crucial to investigate structurally modified analogs of curcumin without such shortcomings. The synth
- Huber, Imre,Rozmer, Zsuzsanna,Gy?ngyi, Zoltán,Budán, Ferenc,Horváth, Péter,Kiss, Eszter,Perjési, Pál
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- Disubstituted aryl compound and application thereof
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The invention relates to bis-substituted aryl compounds and application thereof. The structure of the bis-substituted aryl compounds is disclosed as Formula I, II or III. The experimental verification detects that the bis-substituted aryl compounds can be
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Paragraph 0115-0117
(2019/08/06)
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- Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
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Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.
- Deck, Lorraine M.,Hunsaker, Lucy A.,Vander Jagt, Thomas A.,Whalen, Lisa J.,Royer, Robert E.,Vander Jagt, David L.
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p. 854 - 865
(2017/12/13)
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- For anti-tumor N - methyl - 3, 5 - aryl methylene - 4 - piperidone and its quaternary ammonium salt derivatives
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The invention relates to antitumor drugs and particularly relates to an anti-tumor N-methyl-3,5-diarylmethylene-4-piperidone and quaternary ammonium derivatives thereof. The preparation method comprises the following steps of carrying out Claisen-Schmidt
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Paragraph 0064-0066
(2017/10/13)
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- Synthesis, Antiproliferative, and Multidrug Resistance Reversal Activities of Heterocyclic α,β-Unsaturated Carbonyl Compounds
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A series of heterocyclic α,β-unsaturated carbonyl compounds (1a-1d, 2a-2d, 3a-3d, 4a-3d, and 5a-5d) with 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore were synthesized for the development of anticancer and multidrug resistance reverting agents. The antiproliferative activities were tested against nine human cancer cell lines. Approximately 73% of the IC50 values were below 5 μm, while 35% of these figures were submicromolar, and compounds 3a-3d with 4-trifluoro methyl in the arylidene benzene rings were the most potent, since their IC50 values are between 0.06 and 3.09 μm against all cancer cell lines employed. Meanwhile, their multidrug resistance reversal properties and cellular uptake were further examined. The data displayed that all of these compounds could reverse multidrug resistance, particularly, compounds 3a and 4a demonstrated both potent multidrug resistance reverting properties and strong antiproliferative activities, which can be taken as leading molecules for further research of dual effect agents in tumor chemotherapy.
- Sun, Ju-feng,Hou, Gui-ge,Zhao, Feng,Cong, Wei,Li, Hong-juan,Liu, Wen-shuai,Wang, Chunhua
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p. 534 - 541
(2016/10/06)
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- Synthesis and molecular modeling studies of indole-based antitumor agents
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Indole-based compounds 30-63 were synthesized by the multi-component 1,3-dipolar cycloaddition reaction of 1-alkyl-3,5-bis(arylidene)-4-piperidones 11-25 with azomethine ylides (generated by the condensation of isatins 26-28 with sarcosine 29). The single crystal X-ray studies of 46 and 48 supported the regio- and stereoselectivity of the reaction. Most of the synthesized spiro-indoles exhibited potent antitumor properties against the HeLa (cervical cancer) cell line through in vitro sulfo-rhodamine-B bioassay, higher than that of cisplatin. Only compound 54 showed bio-potency against the HepG2 (hepatocellular cancer) cell line, comparable to that of doxorubicin hydrochloride (standard reference). 3D-Pharmacophore and 2D-QSAR studies were used to validate the observed biological data and determine the most important parameters controlling activity. The estimated bio-properties from the computational studies showed high approximations to the experimental data.
- George, Riham F.,Panda, Siva S.,Shalaby, El-Sayed M.,Srour, Aladdin M.,Farag, I. S. Ahmed,Girgis, Adel S.
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p. 45434 - 45451
(2016/06/06)
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- Synthesis and biological evaluation of new curcumin analogues as antioxidant and antitumor agents: Molecular modeling study
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New curcumin analogues have been synthesized and their antioxidant activities were investigated by measuring their free radical scavenging capacities. The in vitro and in vivo antitumor activities of the synthesized compounds on Ehrlich ascites carcinoma (EAC) cell line were evaluated. 4-(4-Chlorophenyl)-2-(5-ethyl-7-(4-methoxybenzylidene)-3-(4-methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c] pyridin-2-yl)thiazole 7h showed excellent antineoplastic activity in both in vitro and in vivo studies more than that of tested compounds and reference drug, cisplatin. Different molecular modeling studies were performed, where docking of compound 7h into telomerase active site suggested that it could exert its antitumor potential by telomerase inhibition.
- Bayomi, Said M.,El-Kashef, Hassan A.,El-Ashmawy, Mahmoud B.,Nasr, Magda N.A.,El-Sherbeny, Magda A.,Abdel-Aziz, Naglaa I.,El-Sayed, Magda A.-A.,Suddek, Ghada M.,El-Messery, Shahenda M.,Ghaly, Mariam A.
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p. 584 - 594
(2015/07/28)
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- Amino functionalized mesoporous silica decorated with iron oxide nanoparticles as a magnetically recoverable nanoreactor for the synthesis of a new series of 2,4-diphenylpyrido[4,3-d]pyrimidines
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(Fe2O3)-MCM-41-nPrNH2 as a magnetically recoverable nanoreactor, was prepared through the reaction of (Fe 2O3)-MCM-41 with 3-aminopropyltriethoxysilane in refluxing dry toluene. The catalyst with 10 wt% of loaded iron oxide nanoparticles was found to be a highly efficient nanocatalyst for the synthesis of a new class of 2,4-diphenylpyrido[4,3-d]pyrimidines under solvent free conditions in high to quantitative yields. By using an external magnet the catalyst was recovered and reused several times without any loss of efficiency. The prepared catalyst was characterized by transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray powder diffraction (XRD), and nitrogen physisorption measurements.
- Shadjou, Nasrin,Hasanzadeh, Mohammad
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p. 18117 - 18126
(2014/05/20)
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- Microwave-assisted synthesis of pyrimido[4,5-b][1,6]naphthyridin-4(3H)-ones with potential antitumor activity
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The 6,7,8,9-tetrahydropyrimido[4,5-b][1,6]naphthyridin-4(3H,5H,10H)-ones 4,5a-g and their oxidized forms 6,7a-g were obtained from the catalyst-free reaction of 6-amino-2-methylthiopyrimidin-4(3H)-one 3 and (E)-3,5- bis(benzylidene)-1-alkyl-4-piperidones
- Insuasty, Braulio,Becerra, Diana,Quiroga, Jairo,Abonia, Rodrigo,Nogueras, Manuel,Cobo, Justo
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- Application of MCM-41-SO3H as an advanced nanocatalyst for the solvent free synthesis of pyrano[3,2-c]pyridine derivatives
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MCM-41-SO3H, an ordered mesoporous silica material in which MCM-41 with covalently anchored sulfonic acid groups was used as an acidic catalyst for the rapid and 'green' synthesis of pyrano[3,2-c]pyridine derivatives under solvent-free conditions. Reusability of the catalyst, high yields, short reaction times, simplicity and easy workup are advantages of this novel synthetic procedure compared to the conventional methods reported in the literature.
- Rostamizadeh, Shahnaz,Shadjou, Nasrin,Hasanzadeh, Mohammad
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experimental part
p. 866 - 871
(2012/08/07)
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- A highly atom economic, chemo-, regio- and stereoselective synthesis and evaluation of spiro-pyrrolothiazoles as antitubercular agents
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The 1,3-dipolar cycloaddition of azomethine ylides derived from substituted isatins and 1,3-thiazolane-4-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolothiazoles chemo-, regio- and stereoselectively in quantitative yields. These compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB) using agar dilution method. Among the synthesized compounds, spiro[5.3′′]-5′′-nitrooxindole-spiro-[6.3′]-1′-methyl-5′-(2,4-di-chlorophenylmethylidene)tetrahydro-4′(1H)-pyridinone-7-(2,4-dichlorophenyl)tetra-hydro-1H-pyrrolo[1,2-c][1,3]thiazole (9k) was found to be the most active with a minimum inhibitory concentration (MIC) of 0.6 μM against MTB and MDR-TB.
- Karthikeyan, Subramanian Vedhanarayanan,Bala, Balasubramanian Devi,Raja, Velanganni Paul Alex,Perumal, Subbu,Yogeeswari, Perumal,Sriram, Dharmarajan
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supporting information; experimental part
p. 350 - 353
(2010/04/05)
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- The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones
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This study demonstrated that replacement of the axial protons on the C2 and C6 atoms of various 1-methyl-3,5-bis(benzylidene)-4-piperidones 3 by a dimethylene bridge leading to series 2 lowered cytotoxic potencies. Four compounds 2a and 3a-c emerged as lead molecules based on their toxicity towards different neoplasms and their selective toxicity for malignant rather than normal cells. Some possible reasons for the disparity between the IC50 values in the two series of compounds are presented based on molecular modeling, log P values and respiration in rat liver mitochondria.
- Pati, Hari N.,Das, Umashankar,Das, Swagatika,Bandy, Brian,De Clercq, Erik,Balzarini, Jan,Kawase, Masami,Sakagami, Hiroshi,Quail, J. Wilson,Stables, James P.,Dimmock, Jonathan R.
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experimental part
p. 54 - 62
(2009/04/07)
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- An efficient and chemoselective synthesis of 1,6-naphthyridines and pyrano[3,2-c]pyridines under microwave irradiation
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A series of 1,6-naphthyridines and pyrano[3,2-c]pyridines were selectively synthesized via microwave-assisted reactions controlled by the nature of the solvent. This has resulted in an efficient and promising synthetic method for constructing the 1,6-naph
- Han, Zheng-Guo,Tu, Shu-Jiang,Jiang, Bo,Yan, Shu,Zhang, Xiao-Hong,Wu, Shan-Shan,Hao, Wen-Juan,Cao, Xu-Dong,Shi, Feng,Zhang, Ge,Ma, Ning
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experimental part
p. 1639 - 1646
(2009/12/09)
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- Synthesis and biological evaluation of some polymethoxylated fused pyridine ring systems as antitumor agents
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A series of 3,5-bis(arylidene)-4-piperidones like chalcone analogues carrying variety of methoxylated aryl groups, pyrazolo[4,3-c]pyridines, pyrido[4,3-d]pyrimidines, and pyrido[3,2-c]pyridines, carrying an arylidene moiety, and some pyrano[3,2-c]pyridine
- Rostom, Sherif A. F.,Hassan, Ghada S.,El-Subbagh, Hussein I.
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scheme or table
p. 584 - 590
(2009/12/10)
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- Discovery of antimycobacterial spiro-piperidin-4-ones: An atom economic, stereoselective synthesis, and biological intervention
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An atom economic and stereoselective synthesis of several spiro-piperidin-4-ones through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin and α-amino acids viz. proline, phenylglycine, and sarcosine to a series of 1-methyl-3,5-bis[(E)- arylmethylidene]tetrahydro-4(1H)-pyridinones is described. These compounds were evaluated for their in vitro and in vivo activity against Mycobacterium tuberculosis H37Rv (MTB), multidrug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2). Compound 4-(4-fluorophenyl)-5-phenylpyrrolo(spiro[2.3″]oxindole)spiro[3.3′] -1′-methyl-5′-(4-fluorophenylmethylidene)piperidin-4′-one (4e) was found to be the most active in vitro with a MIC value of 0.07 μM against MTB and was 5.1 and 67.2 times more potent than isoniazid and ciprofloxacin, respectively. In vivo, compound 4e decreased the bacterial load in lung and spleen tissues with 1.30 and 3.73-log 10 protections respectively and was considered to be promising in reducing bacterial count in lung and spleen tissues.
- Kumar, Raju Ranjith,Perumal, Subbu,Senthilkumar, Palaniappan,Yogeeswari, Perumal,Sriram, Dharmarajan
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experimental part
p. 5731 - 5735
(2009/09/25)
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- Synthesis and spectroscopic and structural studies of cross-conjugated dienones derived from cyclic ketones and aromatic aldehydes
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Cross-conjugated dienones were synthesized by the reactions of cyclic ketones with two equivalents of aromatic aldehydes under basic conditions. An NMR spectroscopic study and X-ray diffraction analysis demonstrated that all reaction products are formed as E,E isomers. Spontaneous photochemical trans-cis isomerization of cross-conjugated dienones under the scattered light in solution was observed for the first time. The degree of isomerization depends mainly on the nature of the central fragment of the dienone molecule. The previously unknown product of photochemical [2+2]-cycloaddition of 2,5-bis[(E)-(3-pyridyl)methylidene]cyclopentanone was synthesized and characterized by spectroscopic methods and X-ray diffraction. Under the conditions used, only one isomer of the cyclobutane adduct was obtained. Springer Science+Business Media, Inc. 2006.
- Vatsadze,Manaenkova,Sviridenkova,Zyk,Krut'ko,Churakov,Antipin,Howard,Lang
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p. 1184 - 1194
(2008/02/02)
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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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- Ene reactions of arylmethylenedihydropyrazoles with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione
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2-Acetyl-3-aryl-7-arylmethylene-3,4,5,6,7,9-hexahydro-2H-indazoles enter into the ene reaction with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione to give the corresponding monoene adducts. Under analogous conditions, 3-aryl-7-arymethylene-2-methyl-3,4,5,6,7,9-hexahydro-2H-indazoles give mono- and polyaddition products. The structures of compounds obtained were established using UV, IR, 1H and 13C NMR spectroscopy and X-ray diffraction analysis.
- Klimova,Martinez,Klimova,Damian,Ortega,Mendez,Gutiérrez,Vazquez
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p. 1891 - 1897
(2007/10/03)
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- Ene synthesis of bicyclic arylmethylenedihydropyrazoles using 4-phenyl-4,5-dihydro-3H-1,2,4-triazole-3,5-dione
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8-Acetyl-7-aryl-2-arylmethylene-8,9-diaza- and 4,8,9-triazabicyclo[4.3.0]non-9-enes react with 4-phenyl-4,5-dihydro-3H-1,2,4-triazole-3,5-dione, following the ene addition pattern. Under similar conditons 7-aryl-2-arylmethylene-8-methyl-8,9-diazabicyclo[4.3.0]non-9-enes give rise to both mono- and polyaddition products. The product structures were studied by 1H and 13C NMR, IR, and UV spectroscopy and single crystal X-ray diffraction.
- Martinez,Klimova-Berestneva,Damian-Zea,Meleshonkova,Klimova
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p. 1132 - 1140
(2007/10/03)
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- Synthesis and biological evaluation of certain α,β-unsaturated ketones and their corresponding fused pyridines as antiviral and cytotoxic agents
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A new series of 3,5-bis(arylidene)-4-piperidones, as chalcone analogues carrying variety of aryl and heteroaryl groups, pyrazolo[4,3-c]pyridines, pyrido[4,3-d]pyrimidines, and pyrido[3,2-c]-pyridines, carrying an arylidene moiety, and a series of pyrano[3
- El-Subbagh, Hussein I.,Abu-Zaid, Suhair M.,Mahran, Mona A.,Badria, Farid A.,Al-Obaid, Abdulrahman M.
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p. 2915 - 2921
(2007/10/03)
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