Synthesis, biological evaluation, and molecular docking investigation of 3-amidoindoles as potent tubulin polymerization inhibitors.


:A series of novel 3-amidoindole derivatives possessing 3,4,5-trimethoxylphenyl groups were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Some of them demonstrated moderate to potent activities in vitro against six cancer cell lines including MCF-7, MDA-MB-231, BT549, T47D, MDA-MB-468, and HS578T. The most active compound 27 inhibited the growth of T47D, BT549, and MDA-MB-231 cell lines with IC50 values at 0.04, 3.17, and 6.43 μM, respectively. Moreover, the flow cytometric analysis clearly revealed that compound 27 significantly inhibited growth of breast cancer cells through arresting cell cycle in G2/M phase via a concentration-dependent manner. In addition, the compound also exhibited the most potent anti-tubulin activity with IC50 values of 9.5 μM, which was remarkable, compared to CA-4. Furthermore, molecular docking analysis demonstrated the interaction of the compound 27 at the colchicine-binding site of tubulin. These preliminary results suggest that compound 27 is a very promising tubulin-binding agent and is worthy of further investigation aiming to the development of new potential anticancer agents.


Eur J Med Chem


Chen P,Zhuang YX,Diao PC,Yang F,Wu SY,Lv L,You WW,Zhao PL




Has Abstract


2019-01-15 00:00:00












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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ansari KF,Lal C

    更新日期:2009-05-01 00:00:00

  • Synthesis, local anaesthetic and antiarrhythmic activities of N-alkyl derivatives of proline anilides.

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    pub_type: 杂志文章


    authors: Kalinin DV,Pantsurkin VI,Syropyatov BY,Kalinina SA,Rudakova IP,Vakhrin MI,Dolzhenko AV

    更新日期:2013-05-01 00:00:00

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    abstract::Twenty-eight structurally diverse cytochrome 3A4 (CYP3A4) inhibitors have been subjected to quantitative structure-activity relationship (QSAR) studies. The analyses were performed with electronic, spatial, topological, and thermodynamic descriptors calculated using Cerius 2 version 10 software. The statistical tools ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Roy K,Pratim Roy P

    更新日期:2009-07-01 00:00:00

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    abstract::A series of 32 derivatives and isosteres of the mTOR inhibitor 2 were synthesized and compared for their cytotoxicity in radioresistant SQ20B cancer cell line. Several of these compounds, in particular 30b, were significantly more cytotoxic than 2. Importantly, 30b was shown to block both mTORC1 and Akt signaling, sug...

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    pub_type: 杂志文章


    authors: Salomé C,Ribeiro N,Chavagnan T,Thuaud F,Serova M,de Gramont A,Faivre S,Raymond E,Désaubry L

    更新日期:2014-06-23 00:00:00

  • Pyridazine as a privileged structure: An updated review on anticancer activity of pyridazine containing bioactive molecules.

    abstract::Identification of potent anticancer agents with high selectivity and low toxicity remains on the way to human health. Pyridazine featuring advantageous physicochemical properties and antitumor potential usually is regarded as a central core in numerous anticancer derivatives. There are several approved pyridazine-base...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: He ZX,Gong YP,Zhang X,Ma LY,Zhao W

    更新日期:2021-01-01 00:00:00

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    abstract::Classification models of estrogen receptor-beta ligands were proposed using linear and nonlinear models. The data set was divided into active and inactive classes on the basis of their binding affinities. The two-class problem (active, inactive) was firstly explored by linear classifier approach, linear discriminant a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Luan F,Liu HT,Ma WP,Fan BT

    更新日期:2008-01-01 00:00:00

  • Design, synthesis and bioactivities of TAR RNA targeting beta-carboline derivatives based on Tat-TAR interaction.

    abstract::A series of new beta-carboline derivatives 3-14 bearing guanidinium group or amino group-terminated side chain targeting the TAR RNA were designed and synthesized. Molecular modeling studies indicated that the minimal interaction energy was obtained for compound 11, which contained the optimal linker of three methylen...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yu X,Lin W,Pang R,Yang M

    更新日期:2005-09-01 00:00:00

  • Design and synthesis of pironetin analogue/combretastatin A-4 hybrids containing a 1,2,3-triazole ring and evaluation of their cytotoxic activity.

    abstract::We here describe the preparation of a series of hybrid molecules containing a combretastatin A-4 moiety and a pironetin analogue fragment connected through a spacer of variable length which includes a 1,2,3-triazole ring. The cytotoxic activities of these compounds have been measured. Relations between structure and c...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Vilanova C,Torijano-Gutiérrez S,Díaz-Oltra S,Murga J,Falomir E,Carda M,Alberto Marco J

    更新日期:2014-11-24 00:00:00

  • Design, selective alkylation and X-ray crystal structure determination of dihydro-indolyl-1,2,4-triazole-3-thione and its 3-benzylsulfanyl analogue as potent anticancer agents.

    abstract::Three sets of substituted indolyl-triazoles were synthesized by the alkylation of 1,2-dihydro-5-(1H-indol-2-yl)-1,2,4-triazole-3-thione with different alkyl halides. The use of pyridine restricted the alkylation to sulfur. Whereas, upon using K2CO3, the alkylation exceeded sulfur to one of the remaining triazole nitro...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Boraei AT,Gomaa MS,El Ashry ES,Duerkop A

    更新日期:2017-01-05 00:00:00

  • Synthesis, antiarrhythmic and anticoagulant activities of novel thiazolo derivatives from methyl 2-(thiazol-2-ylcarbamoyl)acetate.

    abstract::A series of novel thiazolo derivatives were synthesized by initial condensation of methyl 2-(thiazol-2-ylcarbamoyl)acetate with phenyl isothiocyanate and further reactions using different organic reagents. The structures of newly synthesized compounds were confirmed by IR, 1H NMR, EIMS spectral data and elemental anal...

    journal_title:European journal of medicinal chemistry

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    authors: Amr Ael-G,Sabrry NM,Abdalla MM,Abdel-Wahab BF

    更新日期:2009-02-01 00:00:00

  • Green synthesis and antimicrobial evaluation of some new trifluoromethyl-substituted hexahydropyrimidines by grinding.

    abstract::A series of trifluoromethyl-substituted hexahydropyrimidine derivatives were efficiently synthesized in excellent yields via one-pot three-component reaction of aromatic aldehydes, ethyl trifluoroacetoacetate and thiourea(urea) in presence of p-toluenesulfonic acid under solvent-free conditions at room temperature by ...

    journal_title:European journal of medicinal chemistry

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    authors: Zohdi HF,Rateb NM,Elnagdy SM

    更新日期:2011-11-01 00:00:00

  • Synthesis and antimicrobial activities of novel 1,5-diaryl pyrazoles.

    abstract::Novel 1,5-diaryl pyrazole derivatives viz. 5-(4-chlorophenyl)-1-(4-fluorophenyl)-1H-pyrazole-3-carboxamides (2a-e, 3, 3a-f), 2-(5-(4-chlorophenyl)-1-(4-fluorophenyl)-1H-pyrazole-3-yl)thiazoles (6a-c,7, 8, 9a-c, 10, 11) were synthesized by varying the active part (amide group) of pyrazole, characterized using IR, (1)H ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ragavan RV,Vijayakumar V,Kumari NS

    更新日期:2010-03-01 00:00:00

  • In vitro PAI-1 inhibitory activity of oxalamide derivatives.

    abstract::A number of oxalamide derivatives have been synthesized and evaluated for PAI-1 inhibitory activity. In vitro PAI-1 inhibitory activities of oxalamide derivatives are evaluated by chromogenic assay. Few compounds have shown significant PAI-1 inhibitory activity. ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Jain MR,Shetty S,Chakrabarti G,Pandya V,Sharma A,Parmar B,Srivastava S,Raviya M,Soni H,Patel PR

    更新日期:2008-04-01 00:00:00

  • Rational approach to highly potent and selective apoptosis signal-regulating kinase 1 (ASK1) inhibitors.

    abstract::Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down reg...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lovering F,Morgan P,Allais C,Aulabaugh A,Brodfuehrer J,Chang J,Coe J,Ding W,Dowty H,Fleming M,Frisbie R,Guzova J,Hepworth D,Jasti J,Kortum S,Kurumbail R,Mohan S,Papaioannou N,Strohbach JW,Vincent F,Lee K,Zapf CW

    更新日期:2018-02-10 00:00:00

  • Benzotriazole: An overview on its versatile biological behavior.

    abstract::Discovered in late 1960, azoles are heterocyclic compounds class which constitute the largest group of available antifungal drugs. Particularly, the imidazole ring is the chemical component that confers activity to azoles. Triazoles are obtained by a slight modification of this ring and similar or improved activities ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Briguglio I,Piras S,Corona P,Gavini E,Nieddu M,Boatto G,Carta A

    更新日期:2015-06-05 00:00:00

  • Molecular design, synthesis and biological research of novel pyridyl acridones as potent DNA-binding and apoptosis-inducing agents.

    abstract::A series of novel pyridyl acridone derivatives comprised of a pseudo-five-cyclic system to extend the π-conjugated acridone chromophore, were designed and synthesized as potent DNA binding antitumor compounds. Most synthesized compounds displayed good activity against human leukemia K562 cells in MTT tests, with compo...

    journal_title:European journal of medicinal chemistry

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    authors: Zhang B,Chen K,Wang N,Gao C,Sun Q,Li L,Chen Y,Tan C,Liu H,Jiang Y

    更新日期:2015-03-26 00:00:00

  • Synthesis and antibacterial activities of novel pleuromutilin derivatives with a substituted pyrimidine moiety.

    abstract::The alarming growth of multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) has become a major global health hazard. Therefore, urgent demand for new antibiotics with a unique mechanism of action is very necessary. The present study reports ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yi Y,Xu X,Liu Y,Xu S,Huang X,Liang J,Shang R

    更新日期:2017-01-27 00:00:00

  • Design, synthesis and antitumour evaluation of pyrrolo[1,2-f]-phenanthridine and dibenzo[f,h]pyrrolo[1,2-b]isoquinoline derivatives.

    abstract::A series of 1,2-bis(hydroxymethyl)pyrrolo[1,2-f]phenanthridine derivatives and their alkyl (ethyl and isopropyl) carbamates and 12,13-bis(hydroxymethyl)-9,14-dihydro-dibenzo[f,h]pyrrolo[1,2-b]isoquinoline derivatives were synthesized for antiproliferative evaluation. The preliminary antitumour studies revealed that th...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Patel AS,Jain V,Rao VN,Lin YW,Shah A,Lai KC,Su TL,Lee TC

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  • Novel inhibitors of the sodium-calcium exchanger: benzene ring analogues of N-guanidino substituted amiloride derivatives.

    abstract::A series of N-guanidino substituted 2,4-diamino-5-carbonylguanidine molecules related to amiloride were synthesised and evaluated for their ability to inhibit the sodium-calcium exchanger in rat insulinoma cells (RINm5F) and human platelets. Specific chemical pathways were used to prepare the benzene derivatives desig...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rogister F,Laeckmann D,Plasman P,Van Eylen F,Ghyoot M,Maggetto C,Liégeois J,Géczy J,Herchuelz A,Delarge J,Masereel B

    更新日期:2001-07-01 00:00:00

  • Indole based antimalarial compounds targeting the melatonin pathway: Their design, synthesis and biological evaluation.

    abstract::Malaria, one of the most severe global diseases, infects nearly 300 million people causing death of about a million population annually. Herein we have reported design, synthesis and biological evaluation of potent antimalarial compounds that target melatonin hormone as a potential pathway for the inhibition of the pa...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Luthra T,Nayak AK,Bose S,Chakrabarti S,Gupta A,Sen S

    更新日期:2019-04-15 00:00:00

  • Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease.

    abstract::Designing drugs with a specific multi-target profile is a promising approach against multifactorial illnesses as Alzheimer's disease. In this work, new indazole ethers that possess dual activity as both cannabinoid agonists CB2 and inhibitors of BuChE have been designed by computational methods. On the basis of this k...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: González-Naranjo P,Pérez-Macias N,Campillo NE,Pérez C,Arán VJ,Girón R,Sánchez-Robles E,Martín MI,Gómez-Cañas M,García-Arencibia M,Fernández-Ruiz J,Páez JA

    更新日期:2014-02-12 00:00:00

  • Synthesis and antiinflammatory activity of heterocyclic indole derivatives.

    abstract::Chalcones of indole 1-5 and their corresponding products; pyrazolines 6-10 and azo compounds 11-15 were synthesised and evaluated for their antiinflammatory activity against carrageenan induced oedema in albino rats at a dose of 50 mg x kg(-1) oral. The structure of compounds was confirmed by IR, (1)H-NMR and mass spe...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rani P,Srivastava VK,Kumar A

    更新日期:2004-05-01 00:00:00

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Mortazavi H,Nikfar B,Esmaeili SA,Rafieenia F,Saburi E,Chaichian S,Heidari Gorji MA,Momtazi-Borojeni AA

    更新日期:2020-02-01 00:00:00

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Álvarez R,Aramburu L,Gajate C,Vicente-Blázquez A,Mollinedo F,Medarde M,Peláez R

    更新日期:2021-01-01 00:00:00

  • Prenylflavonoids and prenyl/alkyl-phloroacetophenones: synthesis and antitumour biological evaluation.

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Basabe P,de Román M,Marcos IS,Diez D,Blanco A,Bodero O,Mollinedo F,Sierra BG,Urones JG

    更新日期:2010-09-01 00:00:00

  • Dihydropyrimidinone/1,2,3-triazole hybrid molecules: Synthesis and anti-varicella-zoster virus (VZV) evaluation.

    abstract::By combining the structural features of dihydropyrimidinone and 1,2,3-triazole heterocycles, novel hybrid compounds were synthesized using a simple and convenient method. A series of novel mono and bis 1,2,3-triazole was synthesized via copper-catalyzed Huisgen azide-alkyne cycloadditions (CuAAC) under microwave irrad...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kaoukabi H,Kabri Y,Curti C,Taourirte M,Rodriguez-Ubis JC,Snoeck R,Andrei G,Vanelle P,Lazrek HB

    更新日期:2018-07-15 00:00:00

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


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    更新日期:2019-10-01 00:00:00

  • Substitution at the indole 3 position yields highly potent indolecombretastatins against human tumor cells.

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Álvarez R,Gajate C,Puebla P,Mollinedo F,Medarde M,Peláez R

    更新日期:2018-10-05 00:00:00

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    abstract::Pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X₃ receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS inc...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cho JH,Jung KY,Jung Y,Kim MH,Ko H,Park CS,Kim YC

    更新日期:2013-01-01 00:00:00

  • Platinated benzonaphthyridone is a stronger inhibitor of poly(ADP-ribose) polymerase-1 and a more potent anticancer agent than is the parent inhibitor.

    abstract::Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer and other diseases, and lots of efforts have been put into the development of organic compounds as more potent PARP-1 inhibitors. Here we describe a strategy to conveniently obtain metal-based PARP-1 inhib...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wang B,Qian H,Yiu SM,Sun J,Zhu G

    更新日期:2014-01-01 00:00:00