- Synthesis and biological evaluation of novel hybrid compounds derived from gallic acid and the 2-aminothiophene derivatives
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Abstract: Gallic acid (GA) and its benzamide derivatives have a wide variety of biological activities, such as antimicrobial, antioxidant, anticancer. In this study, we have reported the synthesis of some new hybrid compounds comprised of the 2-aminothiophene and GA moieties and evaluation of their cytotoxic activities against HeLa (cervical cancer), HCT116 (human colon cancer), and FT (fibroblast) cell lines as well as antimicrobial activities against some Gram-positive and Gram-negative bacteria. The reaction of some 2-aminothiophene derivatives (previously prepared from the Gewald reaction) with galloyl chloride having the acetylated hydroxyl groups and the subsequent deprotection of the hydroxyl groups gave the desired hybrid compounds. Then, the antimicrobial activity of the compounds was evaluated using disc diffusion and minimum inhibitory concentration assays. Finally, the MTT assay was carried out to evaluate the cytotoxicity of the synthesized compounds on the mentioned cell lines. The structure of the synthesized compounds was elucidated by conventional spectroscopic methods such as NMR, FT-IR, and UV–Vis spectroscopy. All compounds prevented the growth of Staphylococcus coagulase more than the positive control of chloramphenicol, and one compound was more sensitive to the growth of Klebsiella pneumonia compared to the standard antibiotic. All compounds showed acceptable activity against cancer cells. The highest activity was observed against HeLa with an IC50 value of 3.2 μg/mL for compound 3d and against HCT116 with IC50 of 59.4 μg/mL for 3b. The high anticancer activity of compound 3d against HeLa allows us to consider it as a good lead compound for the development of new potent anticancer agents for the treatment of cervical cancer. Graphic abstract: [Figure not available: see fulltext.]
- Falanji, Farahnaz,Hosseyni-Tabar, Seyed Mahmood,Mahdavi, Behnam,Rezaei-Seresht, Esmail,Rezaei-Seresht, Hasan
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p. 809 - 815
(2020/03/11)
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- Design, synthesis, and cytotoxicity screening of 5-aryl-3-(2-(pyrrolyl) thiophenyl)-1, 2, 4-oxadiazoles as potential antitumor molecules on breast cancer MCF-7 cells
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The work representing the design and the cytotoxic screening of synthetic small molecules (SSMs) such as carbonitriles 3a-c, carboximidamides 4a-c, and oxadiazoles 5–19 as antitumor molecules. Molecules 4c, 9, 12, and 14 show promising cytotoxicity profiles against two cell lines higher than prodigiosin (PG). The results of topoisomerase enzyme inhibition assay show that compounds 4c and 14 display potent inhibitory activity in nano-molar concentration. In addition, DNA-flow cytometry and annexin V analysis also display that compounds 4c, 9, 12, and 14 exhibit antiproliferative activities over MCF-7 cells by cell cycle arrest at G1 phase and apoptosis-inducing activity by increasing cell percentages at pre G1 phase. Moreover, Elisa measurement of p53 and apoptosis mediators, show that carboximidamide 4c and oxadiazoles 9, 12, and 14 significantly up-regulate p53 and cell death mediators as puma and Bax/Bcl-2 ratio levels. Subsequently, pro-apoptotic activities are confirmed by active caspase 3/7 percentages green fluorescence assay.
- Abd el hameid, Mohammed K.,Mohammed, Manal R.
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p. 609 - 623
(2019/02/26)
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- Design, Synthesis, and Screening of 5-Aryl-3-(2-(pyrrolyl)thiophenyl)-1,2,4-oxadiazoles as Potential Antitumor Molecules on Breast Cancer MCF-7 Cell Line
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The work reported the design and cytotoxic screening of synthetic small molecules: carbonitriles 3a–c, carboximidamides 4a–c, and oxadiazoles 5–19 as antitumor molecules. Molecules 4c, 9, 12, and 14 show promising cytotoxicity profiles against two cell lines higher than prodigiosin (PG). The results of topoisomerase enzyme inhibition assay show that carboximidamide 4c and oxadiazole 14 display potent inhibitory activity in nano-molar concentration higher than PG. In addition, carboximidamide 4c and oxadiazoles 9, 12, and 14 exhibit antiproliferative activities over MCF-7 cells by cell cycle arrest at G1 phase and apoptosis inducing activity by increasing cell population percentages at pre G1 and G2/M phases as shown by DNA-flow cytometry assay and annexin V analysis. Moreover, measurement of p53 and cell death mediators, show that carboximidamide 4c and oxadiazoles 9, 12, and 14 significantly up-regulate p53, Puma and Bax/Bcl-2 ratio levels. Subsequently, pro-apoptotic activities are confirmed by active caspase 3/7 percentages green fluorescence assay.
- Abd el hameid, Mohammed K.
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p. 1181 - 1195
(2018/12/10)
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- Basic Ionic Liquid [bmIm]OH-Mediated Gewald Reaction as Green Protocol for the Synthesis of 2-Aminothiophenes
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A simple, efficient, and environmental friendly procedure was developed based on the Gewald reaction for the synthesis of 2-aminothiophenes using a basic ionic liquid [bmIm]OH as both catalyst and solvent. Besides being a green protocol, the method offers advantages of successful synthesis of a variety of alkyl, aryl, alkoxy, and alkylamino-2-aminothiophenes in good yields.
- Kaki, Venkata Rao,Akkinepalli, Raghuram Rao,Deb, Pran Kishore,Pichika, Mallikarjuna Rao
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p. 119 - 126
(2015/10/20)
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- A convenient synthesis of new 2-cyanomethylthieno[3,2-e]1[1,2,4]- triazolo[1,5-c]pyrimidine derivatives
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A new series of 2-cyanomethylthienotriazolopyrimidines has been synthesized in good yield through a facile method using substituted aminothiophene-3- carbonitrile as building block and cyanoacetic acid hydrazide as reagent in one framework. The structure of the synthesized compounds was established on the basis of their mass and spectral data.
- Jabli, Dhiab,Dridi, Khaireddine,El Efrit, Mohamed L.
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p. 403 - 408
(2014/05/20)
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- Bovine serum albumin-catalyzed one-pot synthesis of 2-aminothiophenes via Gewald reaction
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A novel bovine serum albumin (BSA)-catalyzed Gewald reaction in one-pot was developed in this work. The influence of reaction conditions including solvent, temperature and catalyst loading was investigated, and 12 multi-substituted 2-aminothiophene derivatives were prepared with moderate to excellent yields. Recycle experiments were designed to demonstrate the reusability of BSA. This novel activity of BSA to catalyze Gewald reaction is of practical significance in expanding the application of biocatalysts.
- Zhao, Dan-Dan,Li, Li,Xu, Fan,Wu, Qi,Lin, Xian-Fu
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- KG-60-piperazine as a new heterogeneous catalyst for gewald three-component reaction
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Piperazine supported on amorphous silica (KG-60-piperazine) as a basic catalyst acts in the Gewald three-component reaction of some aldehydes and ketones with malononitrile as well as ethyl cyanoacetate. The catalyst shows general utility with a variety of starting carbonyl compounds. Moreover, the catalyst can be reused for four additional cycles without significant loss of the activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Rezaei-Seresht, Esmail,Tayebee, Reza,Yasemi, Mohammad
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p. 1859 - 1864
(2013/05/21)
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- New insight into adenosine receptors selectivity derived from a novel series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamides and furamides
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A series of [5-substituted-4-phenyl-1,3-thiazol-2-yl] benzamide and furamide analogues were investigated in radioligand binding studies at adenosine receptor subtypes with an aim to obtain potent and selective adenosine receptor ligands. Benzamide and furamide linked to thiazole was found to be crucial for high adenosine receptor affinity. The most potent compound indentified in this study was 5d with low nanomolar affinity for all four adenosine receptor subtypes. Compounds 5a and 5g showed moderate selectivity for A2A adenosine receptors. Molecular docking versus all four human adenosine receptors combined with membrane molecular dynamics studies were performed to rationalise the peculiar selectivity profile of 5d antagonist.
- Inamdar, Gajanan S.,Pandya, Amit N.,Thakar, Hardik M.,Sudarsanam, Vasudevan,Kachler, Sonja,Sabbadin, Davide,Moro, Stefano,Klotz, Karl-Norbert,Vasu, Kamala K.
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p. 924 - 934
(2013/07/27)
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- Mg/La mixed oxide as an efficient heterogeneous basic catalyst for synthesis of 2-aminothiophenes under microwave irradiation
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Microwave-assisted synthesis of 2-aminothiophenes via a Gewald reaction using a heterogeneous strong basic Mg/La mixed oxide catalyst is described.
- Moeinpour, Farid,Dorostkar, Nadieh,Vafaei, Majid
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experimental part
p. 2367 - 2374
(2012/06/18)
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- A facile and practical one-pot synthesis of multisubstituted 2-aminothiophenes via imidazole-catalyzed Gewald reaction
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A simple and efficient procedure was developed for the synthesis of multisubstituted 2-aminothiophene derivatives. In the presence of catalytic amount of imidazole, ketones or aldehydes, dicyanomethane and elemental sulfur were converted into the corresponding 2-aminothiophene derivatives in moderate to high yields in DMF at 60 °C.
- Huang, Xian-Gui,Liu, Jia,Ren, Jiangmeng,Wang, Tao,Chen, Weidong,Zeng, Bu-Bing
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experimental part
p. 6202 - 6205
(2011/09/19)
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- 2-Aminothiophene derivatives in a novel synthesis of phthalimidines
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New aminophthalides were synthesized from o-formylbenzoic acid and substituted 2-aminothiophenes. Two of these compounds underwent recyclization in boiling Ac2O to give the previously unknown 3-acetoxy-2-(3-cyano-4, 5-dimethylthiophen-2-yl)-1,3-dihydroisoindol-1-one and 3-acetoxy-2-(3-cyano-4,5- tetramethylenethiophen-2-yl)-1,3-dihydroisoindol-1-one. The possible reaction mechanism and factors preventing the recyclization, in particular, the formation of intramolecular hydrogen bonds in the starting phthalides, were discussed. Some reactions of the resulting compounds with C-nucleophiles in trifluoroacetic acid were investigated. Two derivatives containing 4-hydroxy-3,5-di-tert- butylphenyl substituents were studied by X-ray diffraction.
- Ukhin,Shepelenko,Belousova,Orlova,Borodkin,Suponitsky
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body text
p. 352 - 360
(2011/11/05)
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- Design, synthesis, and molecular-modeling study of aminothienopyridine analogues of tacrine for Alzheimer's disease
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2-Amino-3-cyanothiophenes were successfully condensed with a number of cycloalkanones to afford tacrine analogues in a one-step reaction mediated with Lewis acid. The newly synthesized compounds have been tested for their ability to inhibit acetylcholine esterase (AChE) activity using tacrine as standard drug. Some of the tested compounds showed moderate inhibitory activity in comparison with tacrine, especially compounds 6a which displayed the highest inhibitory activity. Furthermore, molecular-modeling studies were performed in order to rationalize the obtained biological results.
- Badran, Mohga M.,Hakeem, Maha Abdel,Abuel-Maaty, Suzan M.,El-Malah, Afaf,Salam, Rania M. Abdel
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scheme or table
p. 590 - 601
(2011/06/26)
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- Iodine catalysed synthesis and antibacterial evaluation of thieno-[2,3-d]pyrimidine derivatives
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A new route via iodine catalysed heterocyclisation of 2-amino-4,5- dimethylthiophene-3-carboxamide with aromatic aldehydes affording a series of thieno[2,3-d]pyrimidine derivatives in a single step have been developed. Some of these compounds exhibited an
- Bakavoli, Mehdi,Bagherzadeh, Ghodsieh,Vaseghifar, Maryam,Shiri, Ali,Pordeli, Parvaneh
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scheme or table
p. 653 - 655
(2010/03/24)
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- MODULATION OF CHEMOSENSORY RECEPTORS AND LIGANDS ASSOCIATED THEREWITH
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The present invention provides screening methods for identifying modifiers of chemosensory receptors and their ligands, e.g., by determining whether a test entity is suitable to interact with one or more interacting sites within the Venus flytrap domains of the chemosensory receptors as well as modifiers capable of modulating chemosensory receptors and their ligands.
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Page/Page column 57
(2009/01/20)
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- Synthesis of substituted amino-cycloalkyl[b]thieno-[3,2-e]pyridines
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(Chemical Equation Presented) An efficient two respectively three steps procedure for the synthesis of cycloalkyl[b]thieno[3,2-e]-pyridine amines was developed and in general good to very good yields were obtained.
- Seek, Pierre,Thomae, David,Kirsch, Gilbert
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p. 853 - 857
(2008/09/21)
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- Microwave accelerated Gewald reaction: synthesis of 2-aminothiophenes
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Microwave-promoted synthesis of 2-aminothiophenes by multicomponent reactions of a ketone with an active nitrile and elemental sulfur under KF-alumina catalysis is described.
- Sridhar, Madabhushi,Rao, Rayankula Mallikarjuna,Baba, Nanduri H.K.,Kumbhare, Ravindra M.
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p. 3171 - 3172
(2007/10/03)
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- FUNGICIDES
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A method of combating phytopathogenic diseases on plants and harvested food crops which comprises applying to a plant, to the seed of a plant, to the locus of the plant or seed or to a harvested crop a fungicidally effective amount of 2-aminothiophene derivatives of formula (1). The invention further relates to fungicidal compositions containing these compounds, processes for preparing these compounds and to some of the compounds themselves.
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Page/Page column 107
(2010/02/11)
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- Fused pyrimidines: Part-I: Synthesis of imidazo[1,2-a]thieno[2,3-d]- pyrimidin-5(1H)-imine and pyrimido[1,2-a] thieno[2,3-d] pyrimidin-6-imine
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Annelating reagents, 2-(methylthio)-2-imidazoline (2) and 1,4,5,6-tetrahydro-2-methylthiopyrimidine (4) were prepared from 1,2-diaminoethane and 1,3-diaminopropane via 2-imidazolidinethione and 1,4,5,6-tetrahydropyrimidin-2-thione respectively. The substrate, 2-amino-4,-5-dimethylthiophen-3-carbonitrile (5) was prepared from butanone. The reaction of substrate (5) with the annelating reagents,(2) and (4), in HMPT led to 2,3-dihydro-6,7-dimethylimidazo[1,2-a]thieno[2,3-d]pyrimidin-5(1H)-imine (6) and 1,2,3,4-tetrahydro-7,8-dimethylpyrimido[1,2-a]thieno[2,3-d]pyrimidin-6- imine (7) in good yields.
- Bhuiyan,Rahman, Khandker M. M.,Hossain,Fakruddin
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p. 256 - 258
(2007/10/03)
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- Organic reactions in ionic liquids: Gewald synthesis of 2-aminothiophenes catalyzed by ethylenediammonium diacetate
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Ionic liquids based on 1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF4) and 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) were used as reusable alternatives to volatile organic solvents (VOCs) for ethylenediammonium diacetate (EDDA) catalyzed Gewald synthesis of 2-aminothiophenes. Significant rate enhancement and improvement of the yield were observed. The ionic liquids containing catalyst EDDA were recycled several times with no decreases in yields and reaction rates.
- Hu, Yi,Chen, Zhen-Chu,Le, Zhang-Gao,Zheng, Qin-Guo
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p. 3801 - 3806
(2007/10/03)
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- Novel substituted 3-cyanothiophene acetamides as glucagon receptor antagonists
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The present invention relates to compounds of formula (I) wherein R1, R2, R3, R4 and n are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the antagonism of the glucagon receptor, such as diabetes.
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Page/Page column 5
(2008/06/13)
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- Calcined Mg-Al hydrotalcite as a heterogeneous base catalyst for gewald aminothiophene synthesis
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Calcined Mg-Al hydrotalcite (Mg/Al=4) has been conveniently employed as a heterogeneous base catalyst in the synthesis of 2-amino-3-cyanothiophenes adopting a one pot Gewald aminothiophene methodology.
- Rajagopal,Jyothi,Daniel,Srinivasan,Rao
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p. 3113 - 3117
(2007/10/03)
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