New isoxazolidinone and 3,4-dehydro-β-proline derivatives as antibacterial agents and MAO-inhibitors: A complex balance between two activities.


:Among the different classes of antibiotics, oxazolidinone derivatives represent important drugs, since their unique mechanism of action overcomes commonly diffused multidrug-resistant bacteria. Anyway, the structural similarity of these molecules to monoamino oxidase (MAO) inhibitors, like toloxatone and blefoxatone, induces in many cases loss of selectivity as a major concern. A small library of compounds based on isoxazolidinone and dehydro-β-proline scaffold was designed with the aim to obtain antibacterial agents, evaluating at the same time the potential effects of structural features on MAO inhibitory behaviour. The structural modification introduced in the backbone, starting from Linezolid model, lead to a significant loss in antibiotic activity, while a promising inhibitory effect could be observed on monoamino oxidases. These interesting results are also in agreement with docking experiments suggesting a good binding pose of the synthesized compounds into the pocket of the oxidase enzymes, in particular of MAO-B.


Eur J Med Chem


Ferrazzano L,Viola A,Lonati E,Bulbarelli A,Musumeci R,Cocuzza C,Lombardo M,Tolomelli A




Has Abstract


2016-11-29 00:00:00












  • Synthesis and serotonergic activity of variously substituted (3-amido)phenylpiperazine derivatives and benzothiophene-4-piperazine derivatives: novel antagonists for the vascular 5-HT1B receptor.

    abstract::The synthesis and vascular 5-HT(1B) receptor activity of a novel series of substituted 3-amido phenylpiperazine and 4-(4-methyl-1-piperazinyl)-1-benzo[b]thiophene derivatives is described. Modifications to the amido linked sidechains of the 3-amidophenyl-piperazine derivatives and to the 2-sidechain of the 1-benzo[b]t...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Moloney GP,Garavelas A,Martin GR,Maxwell M,Glen RC

    更新日期:2004-04-01 00:00:00

  • Bimetallic titanocene-gold phosphane complexes inhibit invasion, metastasis, and angiogenesis-associated signaling molecules in renal cancer.

    abstract::Following promising recent in vitro and in vivo studies of the anticancer efficacies of heterometallic titanocene-gold chemotherapeutic candidates against renal cancer, we report here on the synthesis, characterization, stability studies and biological evaluation of a new titanocene complex containing a gold-triethylp...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Elie BT,Fernández-Gallardo J,Curado N,Cornejo MA,Ramos JW,Contel M

    更新日期:2019-01-01 00:00:00

  • Synthesis, neuronal activity and mechanisms of action of halogenated enaminones.

    abstract::Due to the excellent anticonvulsant activity of previously synthesized halogenated enaminones, more disubstituted analogs were synthesized and evaluated in vitro. The new enaminones either had no effect, depressed, or enhanced population spike (PS) amplitude in the rat hippocampus in a concentration-dependent manner. ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Edafiogho IO,Qaddoumi MG,Ananthalakshmi KV,Phillips OA,Kombian SB

    更新日期:2014-04-09 00:00:00

  • Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on CoMFA.

    abstract::Various substituted 3-aryl-1-isoquinolinamines were designed and synthesized based on the previously constructed CoMFA model. Most of the synthesized compounds showed excellent potency in eight different human tumor cell lines as expected. In order to find the exact cytotoxic mechanism of these 3-aryl-1-isoquinolinami...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yang SH,Van HT,Le TN,Khadka DB,Cho SH,Lee KT,Lee ES,Lee YB,Ahn CH,Cho WJ

    更新日期:2010-11-01 00:00:00

  • Site-directed mutagenesis provides insights into the selective binding of trityl derivatives to Plasmodium falciparum dUTPase.

    abstract::We have previously identified a series of triphenylmethane derivatives of deoxyuridine with antimalarial activity in vitro which selectively inhibit Plasmodium falciparum deoxyuridine triphosphate nucleotidohydrolase (PfdUTPase) compared to the human enzyme. The crystal structure of PfdUTPase in complex with one of th...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Recio E,Musso-Buendía A,Vidal AE,Ruda GF,Kasinathan G,Nguyen C,Ruiz-Pérez LM,Gilbert IH,González-Pacanowska D

    更新日期:2011-08-01 00:00:00

  • Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: synthesis, biological evaluation and molecular modeling studies.

    abstract::Continuous efforts in microwave-assisted synthesis and the structure-activity relationships' (SARs) studies of novel modified 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitriles, allowed identification of new amidine and imidate derivatives as potent and dual CDK1/GSK-3 inhibitors. Combination of lead optimization and mo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Logé C,Testard A,Thiéry V,Lozach O,Blairvacq M,Robert JM,Meijer L,Besson T

    更新日期:2008-07-01 00:00:00

  • Structure-guided design of pyridoclax derivatives based on Noxa / Mcl-1 interaction mode.

    abstract::Protein-protein interactions are attractive targets because they control numerous cellular processes. In oncology, apoptosis regulating Bcl-2 family proteins are of particular interest. Apoptotic cell death is controlled via PPIs between the anti-apoptotic proteins hydrophobic groove and the pro-apoptotic proteins BH3...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Hedir S,De Giorgi M,Fogha J,De Pascale M,Weiswald LB,Brotin E,Marekha B,Denoyelle C,Denis C,Suzanne P,Gautier F,Juin P,Ligat L,Lopez F,Carlier L,Legay R,Bureau R,Rault S,Poulain L,Oliveira Santos JS,Voisin-Chiret

    更新日期:2018-11-05 00:00:00

  • Combretastatin A-4 derived 5-(1-methyl-4-phenyl-imidazol-5-yl)indoles with superior cytotoxic and anti-vascular effects on chemoresistant cancer cells and tumors.

    abstract::5-(1-Methyl-4-phenyl-imidazol-5-yl)indoles 5 were prepared and tested as analogs of the natural vascular-disrupting agent combretastatin A-4 (CA-4). The 3-bromo-4,5-dimethoxyphenyl derivative 5c was far more active than CA-4 with low nanomolar IC50 concentrations against multidrug-resistant KB-V1/Vbl cervix and MCF-7/...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mahal K,Biersack B,Schruefer S,Resch M,Ficner R,Schobert R,Mueller T

    更新日期:2016-08-08 00:00:00

  • The 4-N-acyl and 4-N-alkyl gemcitabine analogues with silicon-fluoride-acceptor: Application to 18F-Radiolabeling.

    abstract::The coupling of gemcitabine with functionalized carboxylic acids using peptide coupling conditions afforded 4-N-alkanoyl analogues with a terminal alkyne or azido moiety. Reaction of 4-N-tosylgemcitabine with azidoalkyl amine provided 4-N-alkyl gemcitabine with a terminal azido group. Click reaction with silane buildi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gonzalez C,Sanchez A,Collins J,Lisova K,Lee JT,Michael van Dam R,Alejandro Barbieri M,Ramachandran C,Wnuk SF

    更新日期:2018-03-25 00:00:00

  • The enhancement of neutron irradiation of HeLa-S cervix carcinoma cells by cell-nucleus-addressed deca-p-boronophenylalanine.

    abstract::Boron neutron capture therapy (BNCT) is an experimental treatment modality which depends on a sufficient cellular uptake of Boron ((10)B) followed by an exposure to a thermal neutron beam from a nuclear reactor. High energetic particles (4He and 7Li) are created during the neutron capture reaction and produce DNA dama...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Braun K,Wolber G,Waldeck W,Pipkorn R,Jenne J,Rastert R,Ehemann V,Eisenmenger A,Corban-Wilhelm H,Braun I,Heckl S,Debus J

    更新日期:2003-06-01 00:00:00

  • Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models.

    abstract::Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-β-d-glucose substituent showed a highly potent neuroprotective effect. Further studies...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gonzalez G,Hodoň J,Kazakova A,D'Acunto CW,Kaňovský P,Urban M,Strnad M

    更新日期:2021-01-16 00:00:00

  • Bivalent bendamustine and melphalan derivatives as anticancer agents.

    abstract::The alkylating agents bendamustine and melphalan are currently used in the treatment of various tumoral diseases. In order to increase their antitumor potency and tumor selectivity both compounds were integrated in structure-activity relationship studies including new drug carrier systems. Here we describe the synthes...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Scutaru AM,Wenzel M,Gust R

    更新日期:2011-05-01 00:00:00

  • Sesquiterpene lactones from Inula falconeri, a plant endemic to the Himalayas, as potential anti-inflammatory agents.

    abstract::A phytochemical investigation of Inula falconeri, a plant endemic to the Himalayas, afforded 10 new sesquiterpenoids and 26 known sesquiterpene lactones, including those bearing guaiane, pseudoguaiane, xanthane, eudesmane, germacrane, rare secocaryophyllane, chromolaevane, and carabrane frameworks. The structures were...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cheng X,Zeng Q,Ren J,Qin J,Zhang S,Shen Y,Zhu J,Zhang F,Chang R,Zhu Y,Zhang W,Jin H

    更新日期:2011-11-01 00:00:00

  • Recent advancement of piperidine moiety in treatment of cancer- A review.

    abstract::Piperidine is an important pharmacophore, a privileged scaffold and an excellent heterocyclic system in the field of drug discovery which provides numerous opportunities in studying/exploring this moiety as an anticancer agent by acting on various receptors of utmost importance. Cancer is an uncontrolled division of c...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Goel P,Alam O,Naim MJ,Nawaz F,Iqbal M,Alam MI

    更新日期:2018-09-05 00:00:00

  • Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research.

    abstract::Triterpenoids are natural products from plants and many other organisms that have various biological activities, such as antitumor, antiviral, antimicrobial, and protective activities. This review covers the synthesis and biological evaluation of pentacyclic triterpene (PT) conjugates with other molecules that have be...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Hodon J,Borkova L,Pokorny J,Kazakova A,Urban M

    更新日期:2019-11-15 00:00:00

  • A novel series of 6-substituted 3-(pyrrolidin-1-ylmethyl)chromen-2-ones as selective monoamine oxidase (MAO) A inhibitors.

    abstract::A series of 6-substituted 3-(pyrrolidin-1-ylmethyl)chromen-2-ones (coumarins) have been synthesized and their inhibitory activity to human monoamine oxidase A (MAO A) and B (MAO B) determined. Incorporation of a basic amino function in the C3 position together with substitution at the C6 position produced novel coumar...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mattsson C,Svensson P,Sonesson C

    更新日期:2014-02-12 00:00:00

  • Synthesis and biological evaluation of novel pyranochalcone derivatives as a new class of microtubule stabilizing agents.

    abstract::Twenty-five novel pyranochalcone derivatives were synthesized and evaluated for their in vitro and in vivo antiproliferative activities. Among them, compound 10i exhibited superior potent activity against 21 tumor cell lines including multidrug resistant phenotype with the IC50 values ranged from 0.09 to 1.30 μM. In a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cao D,Han X,Wang G,Yang Z,Peng F,Ma L,Zhang R,Ye H,Tang M,Wu W,Lei K,Wen J,Chen J,Qiu J,Liang X,Ran Y,Sang Y,Xiang M,Peng A,Chen L

    更新日期:2013-04-01 00:00:00

  • Design, synthesis and docking studies of some novel (R)-2-(4'-chlorophenyl)-3-(4'-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5] imidazo [1,2-c]pyrimidin-4-ol derivatives as antitubercular agents.

    abstract::Filamenting temperature-sensitive mutant (FtsZ) is a novel target for the treatment of tuberculosis. A series of (R)-2-(4'-chlorophenyl)-3-(4'-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5] imidazo[1,2-c]pyrimidin-4-ol derivatives were designed and docked on the FtsZ protein crystal structure (PDB Id: 1RLU, resolution 2.08...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Barot KP,Jain SV,Gupta N,Kremer L,Singh S,Takale VB,Joshi K,Ghate MD

    更新日期:2014-08-18 00:00:00

  • Synthesis and evaluation of novel chlorophyll a derivatives as potent photosensitizers for photodynamic therapy.

    abstract::Chlorophyll a exhibits excellent photosensitive activity in photosynthesis. The unstability limited its application as photoensitizer drug in photodynamic therapy. Here a series of novel chlorophyll a degradation products pyropheophorbide-a derivatives were synthesized and evaluated for lung cancer in PDT. These compo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gao YH,Zhu XX,Zhu W,Wu D,Chen DY,Yan YJ,Wu XF,O'Shea DF,Chen ZL

    更新日期:2020-02-01 00:00:00

  • Synthesis, cytotoxicity and DNA-binding levels of new type binuclear platinum(II) complexes.

    abstract::Six new type binuclear platinum(II) complexes (a-f) have been synthesized and characterized by elemental analysis, conductivity, thermal analysis, IR, UV, (1)H NMR and mass spectra techniques. The cytotoxicity of the complexes was tested by MTT and SRB assays. The cell cycle analysis and the levels of total platinum b...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang J,Li Y,Sun J,Li W,Gong Y,Zheng X,Cui J,Wang R,Wu J

    更新日期:2009-11-01 00:00:00

  • Addition of thiols to o-quinone methide: new 2-hydroxy-3-phenylsulfanylmethyl[1,4]naphthoquinones and their activity against the human malaria parasite Plasmodium falciparum (3D7).

    abstract::A series of 36 new phenylsulfanylmethyl[1,4]naphthoquinones (7-42) were synthesized by a three-component reaction that involves lawsone, the appropriate aldehyde and thiols with variable substitution patterns. These reactions involve the in situ generation of o-quinone methides (o-QM) via Knoevenagel condensation and ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sharma A,Santos IO,Gaur P,Ferreira VF,Garcia CR,da Rocha DR

    更新日期:2013-01-01 00:00:00

  • Structure-activity relationship studies and pharmacological characterization of N5-heteroarylalkyl-substituted-2-(2-furanyl)thiazolo[5,4-d]pyrimidine-5,7-diamine-based derivatives as inverse agonists at human A2A adenosine receptor.

    abstract::This paper describes the synthesis and characterization of N5-(hetero)arylalkyl-substituted-thiazolo [5,4-d]pyrimidine-5,7-diamine derivatives (4-19) as novel human (h) A2A adenosine receptor (AR) inverse agonists. Competition binding and cyclic AMP assays indicate that the examined compounds behave as hA2A AR inverse...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Varano F,Catarzi D,Vincenzi F,Falsini M,Pasquini S,Borea PA,Colotta V,Varani K

    更新日期:2018-07-15 00:00:00

  • Covalent binding design strategy: A prospective method for discovery of potent targeted anticancer agents.

    abstract::Cancer remains the most serious disease that threatens human health. Molecularly targeted cancer therapies, specifically small-molecule protein kinase inhibitors, form an important part of cancer therapy. Targeted covalent modification represents a proven approach to drug discovery with the recent FDA approvals of afa...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Wang L,Zhao J,Yao Y,Wang C,Zhang J,Shu X,Sun X,Li Y,Liu K,Yuan H,Ma X

    更新日期:2017-12-15 00:00:00

  • Substituted arylsulphonamides as inhibitors of perforin-mediated lysis.

    abstract::The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Spicer JA,Miller CK,O'Connor PD,Jose J,Huttunen KM,Jaiswal JK,Denny WA,Akhlaghi H,Browne KA,Trapani JA

    更新日期:2017-09-08 00:00:00

  • Design, synthesis, and structure-activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents.

    abstract::A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to excellent activity again...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ma J,Chen D,Lu K,Wang L,Han X,Zhao Y,Gong P

    更新日期:2014-10-30 00:00:00

  • Aryl H-Phosphonates 18. Synthesis, properties, and biological activity of 2',3'-dideoxynucleoside (N-heteroaryl)phosphoramidates of increased lipophilicity.

    abstract::Recently, AZT (N-pyridyl)phosphoramidates were reported as a new type of potential anti-HIV therapeutics. In continuation of that work, here we present new (N-heteroaryl)phosphoramidate derivatives of antiviral 2',3'-dideoxynucleosides containing other types of N-heteroaryl moieties, particularly those with higher lip...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kolodziej K,Romanowska J,Stawinski J,Boryski J,Dabrowska A,Lipniacki A,Piasek A,Kraszewski A,Sobkowski M

    更新日期:2015-07-15 00:00:00

  • Discovery of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives as potent anticancer and antimicrobial agents and screening of anti-diabetic activity: synthesis and in vitro biological evaluation. Part 1.

    abstract::Series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate (DDTD) derivatives: azomethines of DDTD (2a-l) have been synthesized and screened for their anticancer, antimicrobial and anti-diabetic activities. The novel synthesized compounds were characterized by (1)H, (13)C NMR, MS and FT-IR analyses. All compounds were e...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Bozorov K,Ma HR,Zhao JY,Zhao HQ,Chen H,Bobakulov K,Xin XL,Elmuradov B,Shakhidoyatov K,Aisa HA

    更新日期:2014-09-12 00:00:00

  • Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay.

    abstract::In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rohe A,Göllner C,Wichapong K,Erdmann F,Al-Mazaideh GM,Sippl W,Schmidt M

    更新日期:2013-03-01 00:00:00

  • Synthesis and biological evaluation of pyrrolo[2,3-b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA.

    abstract::A series of thirty two novel pyrrolo[2,3-b]pyridine analogues synthesized, characterized ((1)H NMR, (13)C NMR and MS) and cytotoxic evaluation of these molecules carried out over a panel of three human cancer cell lines including A549 (lung cancer), HeLa (cervical cancer) and MDA MB-231 (breast cancer), using sulforho...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Narva S,Chitti S,Bala BR,Alvala M,Jain N,Kondapalli VG

    更新日期:2016-05-23 00:00:00

  • Fructose-1,6-bisphosphatase inhibitors: A new valid approach for management of type 2 diabetes mellitus.

    abstract::The rising incidence of diabetes and confines allied with clinical therapies emphasized the need to explore new molecular targets to develop novel, effective and safer antihyperglycemic agents. Excessive endogenous glucose production by gluconeogenesis is a primary determinant of hyperglycemia in patients with type 2 ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Kaur R,Dahiya L,Kumar M

    更新日期:2017-12-01 00:00:00