- Synthesis and antiproliferative activity of cyclic arylidene ketones: a direct comparison of monobenzylidene and dibenzylidene derivatives
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Abstract To give further insight into the influence of the structural modifications of enones and dienones on their antiproliferative properties, 25 derivatives of enones: (E)-2-benzylidene-1-cyclohexanones, (E)-2-benzylidene-1-tetralones, (E)-2-benzylidene-1-indanone, and dienones: (E,E)-2,5- or 2,6-dibenzylidene-1-cyclanones, (E,E)-3,5-dibenzylidene-4-piperidones were synthesized using a newly developed "one-pot" synthetic method. Due to the fact that all of them have the same aryl substituents (phenyl or 4-chlorophenyl) in the arylidene moiety, it is possible to compare the relevant contribution of the single-point structural modifications (type of ring or N-substitution) on their potency on the basis of their IC 50 values. Their antiproliferative activity was evaluated against the following four human adherent cancer cell lines: HeLa, A431, A2780, and MCF7. The cytotoxicity screen has revealed that the dibenzylidene dienones in general dominate the monobenzylidene enones in this respect. The nitrogen-containing heterocyclic dienones at the same time displayed higher inhibitory properties toward these human carcinoma cell lines compared with their homocyclic dienone analogs. One of the eight newly prepared 4-piperidone derivatives, N-(γ-oxobutyl)-(E,E)-3,5-bis(p-chlorobenzylidene)-4-piperidone is as potent a cell growth inhibitor (IC 50 of 0.438-1.409 μM) as the N-methyl-(E,E)-3,5-bis(p-chlorobenzylidene)-4-piperidone (IC 50 of 0.447-1.048 μM), one of the most active among the previously described compounds in this series. Catalytic hydrogen-transfer isomerization of compounds with two exocyclic benzylidene double bonds to derivatives with endocyclic double bonds results in the complete loss of antiproliferative activity. The structural modifications and 50 % inhibitory concentration (IC 50) values resulted in correlations which can promote the design of more potent derivatives of the 4-piperidone dienones.
- Huber, Imre,Zupk, Istvn,Kovcs, Ida J.,Minorics, Renta,Gulys-Fekete, Gergely,Masz, Gbor,Perjsi, Pl
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- Anticancer activities of novel chalcone and bis-chalcone derivatives
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A series of novel chalcones and bis-chalcones containing boronic acid moieties has been synthesized and evaluated for antitumor activity against the human breast cancer MDA-MB-231 (estrogen receptor-negative) and MCF7 (estrogen receptor-positive) cell lin
- Modzelewska, Aneta,Pettit, Catherine,Achanta, Geetha,Davidson, Nancy E.,Huang, Peng,Khan, Saeed R.
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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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- 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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- Microwave accelerated facile and efficient synthesis of piperido[3′,4′:5,6]pyrano[2,3-d] pyrimidinones catalyzed by basic ionic liquid [BMIM]OH
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A basic ionic liquid [BMIM]OH could very efficiently catalyze the synthesis of piperido[3′,4′:5,6]pyrano[2,3-d]pyrimidinone derivatives from pyrano[3,2-c]piperidine analogues and carbonyl compounds. [BMIM]OH acted as a catalyst as well as the reaction medium and could be used for the reactions for five times without any appreciable loss of its catalytic efficiency. The synergic couple of microwave and ionic liquid provided high yields of the product in very short reaction times and allowed easy workup.
- Siddiqui,Srivastava, Arjita,Shamim, Shayna,Srivastava, Anjali,Waseem, Malik A.,Shireen,Rahila,Abumhdi, Afaf A.H.,Srivastava, Anushree,Rai, Pragati
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p. 126 - 135
(2014/01/06)
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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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- Magnetic graphene oxide anchored sulfonic acid as a novel nanocatalyst for the synthesis of N-aryl-2-amino-1,6-naphthyridines
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Magnetic graphene oxide functionalized with sulfonic acid (Fe 3O4-GO-SO3H) was used as a new recyclable nanocatalyst for one-pot synthesis of N-aryl-2-amino-1,6-naphthyridine derivatives under solvent free conditions. The catalyst could be easily recovered from the reaction mixture by an external magnet and reused without significant decrease in activity even after 4 runs. This nanocatalyst exhibited better activities to other commercially available sulfonic acid catalysts.
- Rostamizadeh, Shahnaz,Rezgi, Mina,Shadjou, Nasrin,Hasanzadeh, Mohammad
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p. 1317 - 1322
(2014/04/17)
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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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- Synthesis, cytotoxicity, and structure-activity insight of NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidones
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Twenty-one NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidone analogs of curcumin, 12 of which are novel, were synthesized and evaluated for their cytotoxicity against B16 (murine melanoma) and L1210 (murine lymphoma) cells grown in culture. These curcumi
- Gregory, Matthew,Dandavati, Armaan,Lee, Megan,Tzou, Samuel,Savagian, Mia,Brien, Kimberly A.,Satam, Vijay,Patil, Pravin,Lee, Moses
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p. 5588 - 5597
(2013/12/04)
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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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- An efficient method for synthesis of pyrano[3,2-c]pyridine derivatives under microwave irradiation
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(Chemical Equation Presented) A series of pyrano[3,2-c]pyridine derivatives were synthesized via reactions of 3,5-dibenzylidenepiperidin-4-one and malononitrile in N,N-dimethylformamide under microwave irradiation. It is a simple, efficient, and promising
- Wang, Shu-Liang,Han, Zheng-Guo,Tu, Shu-Jiang,Zhang, Xiao-Hong,Yan, Shu,Hao, Wen-Juan,Shi, Feng,Cao, Xu-Dong,Wu, Shan-Shan
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experimental part
p. 828 - 831
(2009/12/09)
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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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- 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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- 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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