Studies on self-aggregation of anthracycline drugs by restrained molecular dynamics approach using nuclear magnetic resonance spectroscopy supported by absorption, fluorescence, diffusion ordered spectroscopy and mass spectrometry.


:Self-association, a process that competes with binding to DNA and formation of hetero-complexes, is studied in anticancer drugs 4'-epiadriamycin, adriamycin and daunomycin by proton nuclear magnetic resonance spectroscopy. The 2D nuclear Overhauser enhancement spectra yield several intra-molecular and inter-molecular inter-proton connectivities suggesting specific stacking patterns of aromatic chromophores in parallel and anti-parallel orientation. Absorption, emission and diffusion ordered spectroscopy demonstrate the formation of self-aggregates. Electron spray ionization mass spectrometry gives a direct proof of the presence of dimer and absence of higher aggregates. The restrained molecular dynamics simulations show the structural differences between drugs, which have been correlated to the biological action. A clear evidence of reduced cardiotoxicity by 4'-epiadriamycin, as compared to daunomycin and adriamycin, is demonstrated by mass spectrometry data.


Eur J Med Chem


Agrawal P,Barthwal SK,Barthwal R




Has Abstract


2009-04-01 00:00:00














  • PASS-assisted design, synthesis and antioxidant evaluation of new butylated hydroxytoluene derivatives.

    abstract::New multipotent antioxidants (MPAOs), namely 1,3,4-thiadiazoles and 1,2,4-triazoles bearing the well-known free radical scavenger butylated hydroxytoluene (BHT), were designed and synthesized using an acid-(base-) catalyzed intramolecular dehydrative cyclization reaction of the corresponding 1-acylthiosemicarbazides. ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ariffin A,Rahman NA,Yehye WA,Alhadi AA,Kadir FA

    更新日期:2014-11-24 00:00:00

  • Facile synthesis of active antitubercular, cytotoxic and antibacterial agents: a Michael addition approach.

    abstract::Spiro derivatives of oxindole and isoxazole-5-one were synthesized by using Michael addition reaction, highlighting the regioselective approach towards the synthesis of Michael diadduct followed by condensation of Michael diadduct. The spiro compound 4 showed antitubercular activity against Mycobacterium tuberculosis ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chande MS,Verma RS,Barve PA,Khanwelkar RR,Vaidya RB,Ajaikumar KB

    更新日期:2005-11-01 00:00:00

  • Synthesis of [11C]FEDAA1106 as a new PET imaging probe of peripheral benzodiazepine receptor expression.

    abstract::Peripheral benzodiazepine receptor (PBR) is associated with neuroinflammation and tumor progression. [(11)C]DAA1106 and [(18)F]FEDAA1106 are two promising radioligands for positron emission tomography (PET) imaging of PBR. This study was designed to develop a new radiolabeled analog of [(11)C]DAA1106 and [(18)F]FEDAA1...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wang M,Gao M,Hutchins GD,Zheng QH

    更新日期:2009-06-01 00:00:00

  • Synthesis and evaluation of a small library of graftable thrombin inhibitors derived from (L)-arginine.

    abstract::Novel piperazinyl-amide derivatives of N-alpha-(aryl-sulfonyl)-L-arginine were synthesized as graftable thrombin inhibitors, in the context of biomaterials' design. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position and the introduction of a trifluorometh...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Salvagnini C,Gharbi S,Boxus T,Marchand-Brynaert J

    更新日期:2007-01-01 00:00:00

  • Structure-activity analysis of CJ-15,801 analogues that interact with Plasmodium falciparum pantothenate kinase and inhibit parasite proliferation.

    abstract::Survival of the human malaria parasite Plasmodium falciparum is dependent on pantothenate (vitamin B5), a precursor of the fundamental enzyme cofactor coenzyme A. CJ-15,801, an enamide analogue of pantothenate isolated from the fungus Seimatosporium sp. CL28611, was previously shown to inhibit P. falciparum proliferat...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Spry C,Sewell AL,Hering Y,Villa MVJ,Weber J,Hobson SJ,Harnor SJ,Gul S,Marquez R,Saliba KJ

    更新日期:2018-01-01 00:00:00

  • Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties.

    abstract::The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cai P,Fang SQ,Yang HL,Yang XL,Liu QH,Kong LY,Wang XB

    更新日期:2018-09-05 00:00:00

  • Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease.

    abstract::Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lemes LFN,de Andrade Ramos G,de Oliveira AS,da Silva FMR,de Castro Couto G,da Silva Boni M,Guimarães MJR,Souza INO,Bartolini M,Andrisano V,do Nascimento Nogueira PC,Silveira ER,Brand GD,Soukup O,Korábečný J,Romeiro NC,Cas

    更新日期:2016-01-27 00:00:00

  • Synthesis and antiproliferative activity of a series of novel 6-substituted pyrido[3,2-d]pyrimidines as potential nonclassical lipophilic antifolates targeting dihydrofolate reductase.

    abstract::Dihydrofolate reductase (DHFR) has been a well-recognized target for the treatment of many diseases. Based on 8,10-dideazaminopterins, which are classical antifolates that potently inhibit DHFR, we have designed a series of novel 2,4-diamino-6-substituted pyrido[3,2-d]pyrimidines. By removing the glutamate moiety and ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wang M,Yang J,Yuan M,Xue L,Li H,Tian C,Wang X,Liu J,Zhang Z

    更新日期:2017-03-10 00:00:00

  • Pharmacophore model for pentamidine analogs active against Plasmodium falciparum.

    abstract::Pentamidine and its analogs constitute a class of compounds that are known to be active against Plasmodium falciparum, which causes the most dangerous malarial infection. Malaria is a widespread disease known to affect hundreds of millions of people and presents a perceivable threat of spreading. Hence, there is a nee...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Athri P,Wenzler T,Tidwell R,Bakunova SM,Wilson WD

    更新日期:2010-12-01 00:00:00

  • Antivascular and anti-parasite activities of natural and hemisynthetic flavonoids from New Caledonian Gardenia species (Rubiaceae).

    abstract::A series of 16 flavonoids were isolated and prepared from bud exudate of Gardenia urvillei and Gardenia oudiepe, endemic to New Caledonia. Most of them are rare polymethoxylated flavones. Some of these compounds showed noticeable activity against Leishmania (Leishmania) amazonensis, Plasmodium falciparum and Trypanoso...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mai LH,Chabot GG,Grellier P,Quentin L,Dumontet V,Poulain C,Espindola LS,Michel S,Vo HT,Deguin B,Grougnet R

    更新日期:2015-03-26 00:00:00

  • Molecular modelling and conformational analysis of novel glycoprotein (Gp) IIb/IIIa antagonists. Molecular orbital calculation and the condensed heterocyclic derivatives.

    abstract::A naphthalene compound was chosen as lead compound to develop a new series of fibrinogen receptor antagonists. Eight new compounds with different condensed heterocyclic parts were prepared and their in vitro activities were evaluated. 5-Amidinobenzofuran compound 2, 6-amidinobenzothiophene 7, and 5-amidinofuro[2,3-b]p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ono S,Inoue Y,Yoshida T,Kosaka K,Maeda K,Imada T,Fukaya C,Nakamura N

    更新日期:2000-06-01 00:00:00

  • Caffeoylglycolic and caffeoylamino acid derivatives, halfmers of L-chicoric acid, as new HIV-1 integrase inhibitors.

    abstract::Human immunodeficiency virus (HIV) integrase (IN) catalyzes the integration of HIV DNA copy into the host cell DNA. L-Chicoric acid (1) has been found to be one of the most potent HIV-1 integrase inhibitor. Caffeoylglycolic and caffeoylamino acid derivatives' halfmeric structures of L-chicoric acid 2 were synthesized ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lee SU,Shin CG,Lee CK,Lee YS

    更新日期:2007-10-01 00:00:00

  • 2-cinnamamido, 2-(3-phenylpropiolamido), and 2-(3-phenylpropanamido)benzamides: synthesis, antiproliferative activity, and mechanism of action.

    abstract::Several new benzamides 4a-q were synthesized by stirring in pyridine the acid chlorides 3a-q with the appropriate anthranilamide derivatives 2a-g. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Raffa D,Maggio B,Raimondi MV,Cusimano MG,Amico G,Carollo A,Conaldi PG,Bai R,Hamel E,Daidone G

    更新日期:2013-07-01 00:00:00

  • Lipid lowering agents of natural origin: An account of some promising chemotypes.

    abstract::The role of natural products in the drug development and discovery has been phenomenal. There has been an enormous interest in exploring all possible natural sources to identify structures exhibiting pronounced hypolipidemic activity albeit with no toxicity. The present review describes the profile of some interesting...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Singh SP,Sashidhara KV

    更新日期:2017-11-10 00:00:00

  • Design, synthesis and structure-activity relationships of novel 15-membered macrolides: Quinolone/quinoline-containing sidechains tethered to the C-6 position of azithromycin acylides.

    abstract::In the search for novel hybrid molecules by fusing two biologically active scaffolds into one heteromeric chemotype, we found that hybrids of azithromycin and ciprofloxacin/gatifloxacin 26j and 26l can inhibit the supercoiling activity of E. coli gyrase by poisoning it in a way similar to fluoroquinolones. This may mo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Fan BZ,Hiasa H,Lv W,Brody S,Yang ZY,Aldrich C,Cushman M,Liang JH

    更新日期:2020-05-01 00:00:00

  • Synthesis and comparative photodynamic properties of two isosteric alkyl substituted zinc(II) phthalocyanines.

    abstract::The synthesis and photophysical parameters of two novel isosteric cationic zinc(II) phthalocyanines: 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammoniumethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (6) and 2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gauna GA,Marino J,García Vior MC,Roguin LP,Awruch J

    更新日期:2011-11-01 00:00:00

  • Synthesis of sulfamoylbenzamide derivatives as HBV capsid assembly effector.

    abstract::The synthesis of novel series of sulfamoylbenzamides as HBV capsid assembly effector is reported. The structure was divided into five parts which were independently modified as part of our lead optimization. All synthesized compounds were evaluated for their anti-HBV activity and toxicity in human hepatocytes, lymphoc...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sari O,Boucle S,Cox BD,Ozturk T,Russell OO,Bassit L,Amblard F,Schinazi RF

    更新日期:2017-09-29 00:00:00

  • Design, synthesis and hypolipidemic activity of novel 2-(m-tolyloxy) isobutyric acid derivatives.

    abstract::Novel 2-substituted isobutyric acid derivatives were synthesized and their hypolipidemic activity was evaluated in high cholesterol diet fed rat model. The amide 5a was found to decrease the levels of serum total cholesterol, LDL cholesterol and triglycerides in hyperlipidemic rats to a greater degree than the referen...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Idrees GA,Abuo-Rahma Gel-D,Aly OM,Radwan MF

    更新日期:2009-06-01 00:00:00

  • Design, synthesis and preliminary bioactivity evaluations of 8-hydroxyquinoline derivatives as matrix metalloproteinase (MMP) inhibitors.

    abstract::Matrix metalloproteinases (MMPs) play important roles in many diseases including cancer. With moderate metal-binding affinity, 8-hydroxyquinoline has gained much interest in current drug design and development. Specially, it has been reported that 8-hydroxyquinoline derivatives serve as MMP-2 inhibitors with micromola...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chen C,Yang X,Fang H,Hou X

    更新日期:2019-11-01 00:00:00

  • Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells.

    abstract::A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC50 = 5.17 nM) and 7f (IC50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). I...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wang L,Ai M,Yu J,Jin L,Wang C,Liu Z,Shu X,Tang Z,Liu K,Luo H,Guan W,Sun X,Ma X

    更新日期:2019-06-15 00:00:00

  • Design, synthesis and bioevaluation of novel 6-(4-Hydroxypiperidino)naphthalen-2-ol-based potential Selective Estrogen Receptor Modulators for breast cancer.

    abstract::In a study directed towards development of novel Selective Estrogen Receptor Modulators (SERMs), 1-(4-(2-(dialkylamino)ethoxy)benzyl)-6-(4-hydroxypiperidin-1-yl)-2-naphthol and corresponding aryl methyl ethers were synthesized and bioevaluated against the estrogen-responsive human MCF-7 breast cancer cell line. The ph...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Jha A,Yadav Y,Naidu AB,Rao VK,Kumar A,Parmar VS,MacDonald WJ,Too CK,Balzarini J,Barden CJ,Cameron TS

    更新日期:2015-03-06 00:00:00

  • Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents.

    abstract::By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI₅₀...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chen TC,Yu DS,Huang KF,Fu YC,Lee CC,Chen CL,Huang FC,Hsieh HH,Lin JJ,Huang HS

    更新日期:2013-11-01 00:00:00

  • Comparative study of microtubule inhibitors--estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation.

    abstract::The synthetic estramustine (EM) and natural podophyllotoxin (PODO) anti-mitotic agents that inhibit tubulin polymerization are known anticancer agents. As low bioavailability limits their anticancer properties, we investigated whether conjugation with PAMAM dendrimer (D) could enhance the activity of D-EM and D-PODO b...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sk UH,Dixit D,Sen E

    更新日期:2013-10-01 00:00:00

  • Synthesis of some novel chalcones, flavanones and flavones and evaluation of their anti-inflammatory activity.

    abstract::A novel series of synthetic 2'-hydroxychalcones (1a-h), 2'-methoxychalcones (2a-l), flavanones (3a-k) and flavones (4a-f) have been synthesized and evaluated for their anti-inflammatory activity in carrageenan induced rat paw oedema model. Compounds 1a, 1e-g, 2e-g, 3j, and 4f showed potent anti-inflammatory activity c...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Bano S,Javed K,Ahmad S,Rathish IG,Singh S,Chaitanya M,Arunasree KM,Alam MS

    更新日期:2013-07-01 00:00:00

  • Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: synthesis, crystal structure, antitumor activity and DNA interaction.

    abstract::Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu₂(PYP)₂Cl₄] (1), [Cu₄(PYP)₄(ClO₄)₂(H₂O)₂](ClO₄)₂·2H₂O (2), and [Cu₂(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tum...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Huang KB,Chen ZF,Liu YC,Wang M,Wei JH,Xie XL,Zhang JL,Hu K,Liang H

    更新日期:2013-01-01 00:00:00

  • Synthesis, spectroscopic and biological properties of bis(3-arylimidazolidinyl-1)methanes. A novel family of antimicrobial agents.

    abstract::Synthesis, spectroscopic and biological properties of new bis(3-arylimidazolidinyl-1)methanes are described. These compounds were synthesized by condensation reaction between N-arylethylenediamines and formaldehyde. Chemical structures were confirmed by means of their (1)H- and (13)C-NMR and mass spectroscopic data. I...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Perillo I,Repetto E,Caterina MC,Massa R,Gutkind G,Salerno A

    更新日期:2005-08-01 00:00:00

  • QSAR study on tetrahydroquinoline analogues as plasmodium protein farnesyltransferase inhibitors: a comparison of rationales of malarial and mammalian enzyme inhibitory activities for selectivity.

    abstract::The quantitative structure-activity relationships of Plasmodium falciparum and Rat protein farnesyltransferase (PFT) inhibitory activities of 6-cyano-1-(3-methyl-3H-imidazoly-4-ylmethyl)-3-substituted-1,2,3,4-tetrahydroquinoline (THQ) analogues are investigated in order to explore the similarities/deviations between t...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gupta MK,Prabhakar YS

    更新日期:2008-12-01 00:00:00

  • Synthesis and anticancer activity of 6-heteroarylcoumarins.

    abstract::A series of novel 7-hydroxy-8-methyl-coumarins with indole, pyrimidine, pyrazole, pyran, tetrazolo[1,5-a]pyrimidine, pyrimido[1,2-a]benzimidazol, 2-oxo-1,2-dihydropyridine and dihydropyrazolo[3,4-b]pyridine moieties at C6 position of heterocyclic core have been synthesized. Anticancer activity screening on NCI60 cell ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Galayev O,Garazd Y,Garazd M,Lesyk R

    更新日期:2015-11-13 00:00:00

  • One-pot microwave assisted synthesis of new 2-alkoxycarbonylmethylene-4-oxo-1,5-benzo-, naphtho-, and pyridodiazepines and assessment of their cytogenetic activity.

    abstract::1,5-Benzo-, naphtho-, and pyridodiazepines 3 have been synthesized in excellent yields in one-step from the reaction of o-phenylenediamines with acetonedicarboxylates through microwave assisted acid catalysis. In order to ascertain their cytogenetic activity in vitro at doses equivalent to the per os doses of common 1...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Eleftheriadis N,Neochoritis CG,Tsoleridis CA,Stephanidou-Stephanatou J,Iakovidou-Kritsi Z

    更新日期:2013-09-01 00:00:00

  • Peptidomimetics containing a vinyl ketone warhead as falcipain-2 inhibitors.

    abstract::The design, chemical synthesis, and enzymatic activity evaluation of a set of falcipain-2 inhibitors are reported. These compounds contain a proven peptidomimetic recognition motif based on a benzo[1,4]diazepin-2-one (1,4-BDZ) framework built on a dipeptide sequence, and a Michael acceptor terminal moiety capable of d...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ettari R,Zappalà M,Micale N,Grazioso G,Giofrè S,Schirmeister T,Grasso S

    更新日期:2011-06-01 00:00:00