European Journal of Medicinal Chemistry Impact Factor & Information

Publisher: Elsevier

Journal description

The European Journal of Medicinal Chemistry publishes studies on all aspects of medicinal chemistry: Organic synthesis; Biological behavior; Pharmacological activity; Drug design; QSAR; Molecular Modeling; Drug-receptor interactions; Molecular aspects of drug metabolism; Prodrug synthesis and Drug targeting. The journal accepts papers from any country, European or otherwise, and provides a medium for publication of original papers, laboratory notes, short or preliminary communications, new products and invited reviews.

Current impact factor: 3.43

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 3.432
2012 Impact Factor 3.499
2011 Impact Factor 3.346
2010 Impact Factor 3.193
2009 Impact Factor 3.269
2008 Impact Factor 2.882
2007 Impact Factor 2.301
2006 Impact Factor 2.187
2005 Impact Factor 2.022
2004 Impact Factor 1.673
2003 Impact Factor 1.681
2002 Impact Factor 1.705
2001 Impact Factor 1.077
2000 Impact Factor 1.306
1999 Impact Factor 1.074
1998 Impact Factor 1.116
1997 Impact Factor 0.809
1996 Impact Factor 0.675
1995 Impact Factor 0.746
1994 Impact Factor 0.775
1993 Impact Factor 0.716
1992 Impact Factor 0.624

Impact factor over time

Impact factor
Year

Additional details

5-year impact 3.36
Cited half-life 5.30
Immediacy index 0.61
Eigenfactor 0.01
Article influence 0.70
Website European Journal of Medicinal Chemistry website
Other titles European journal of medicinal chemistry (Online), Eur j med chem
ISSN 1768-3254

Publisher details

Elsevier

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Pre-print allowed on any website or open access repository
    • Voluntary deposit by author of authors post-print allowed on authors' personal website, arXiv.org or institutions open scholarly website including Institutional Repository, without embargo, where there is not a policy or mandate
    • Deposit due to Funding Body, Institutional and Governmental policy or mandate only allowed where separate agreement between repository and the publisher exists.
    • Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months .
    • Set statement to accompany deposit
    • Published source must be acknowledged
    • Must link to journal home page or articles' DOI
    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • NIH Authors articles will be submitted to PubMed Central after 12 months
    • Publisher last contacted on 18/10/2013
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: In this article, we describe the preparation and cytotoxic properties of a small focused library of lupane and 18α-oleanane triterpenoids that contain a combination of two structural motifs known to enhance the biological activities. First, we introduced two fluorine atoms to position 2 of the skeleton. Second, we synthesized a set of hemiester prodrugs, which were intended to increase the solubility and activity. Starting from betulin, we obtained two hydroxyketones (derivatives of dihydrobetulinic acid and allobetulin) and their fluorination using DAST provided 2,2-difluoro-3-oxo-compounds as the main products. Then the 3-oxo group in each derivative was reduced by NaBH4 to obtain 3β-hydroxy compounds suitable for modifying by various hemiesters. We prepared 21 compounds, 11 of them new, their cytotoxicity was tested on T lymphoblastic leukemia CCRF-CEM cells first and the most active derivatives were selected for screening on another six tumor and two non-tumor cell lines. All of them showed selectivity against cancer lines with therapeutic index between 2 and 8. All hemiesters had activity in the same range as the free hydroxyl derivatives and they would be suitable prodrugs for future in vivo experiments. Interestingly, all hemiesters of 2,2-difluorodihydrobetulonic acid had higher activity against p53 knock-out p53−/− cancer cell line than against the non-mutated analog. In active derivatives, the cell cycle was analyzed by flow cytometry and several compounds slowed down cell cycle progression through G0/G1 or S-phase.
    European Journal of Medicinal Chemistry 05/2015; 96. DOI:10.1016/j.ejmech.2015.03.068
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypericum ascyron L. has been used as a traditional medicine for the treatment of wounds, swelling, headache, nausea and abscesses in China for thousands of years. However, modern pharmacological studies are still necessary to provide a scientific basis to substantiate their traditional use. In this study, the mechanism underlying the antimicrobial effect of the antibacterial activity compounds from H. ascyron L. was investigated. Bioguided fractionation of the extract from H. ascyron L. afforded antibacterial activity fraction 8. The results of cup plate analysis and MTT assay showed that the MIC and MBC of fraction 8 is 5 mg/mL. Furthermore, using Annexin V-FITC/PI, TUNEL labeling and DNA gel electrophoresis, we found that cell death with apoptosis features similar to those in eucaryon could be induced in bacteria strains after exposure to the antibacterial activity compounds from H. ascyron L. at moderate concentration. In addition, we further found fraction 8 could disrupt the cell membrane potential indicate that fraction 8 exerts pro-apoptotic effects through a membrane-mediated apoptosis pathway. Finally, quercetin and kaempferol 3-O-β-(2″-acetyl)-galactopyranoside, were identified from fraction 8 by means of Mass spectrometry and Nuclear magnetic resonance. To our best knowledge, this study is the first to show that Kaempferol 3-O-β-(2″-acetyl)-galactopyranoside coupled with quercetin had significant antibacterial activity via apoptosis pathway, and it is also the first report that Kaempferol 3-O-β-(2″-acetyl)-galactopyranoside was found in clusiacea. Our data might provide a rational base for the use of H. ascyron L. in clinical, and throw light on the development of novel antibacterial drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 96. DOI:10.1016/j.ejmech.2015.04.035
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this paper, the design, synthesis and biological evaluation of a set of quinazoline-2,4,6-triamine derivatives (1-9) as trypanocidal, antileishmanial and antiplasmodial agents are explained. The compounds were rationalized basing on docking studies of the dihydrofolate reductase (DHFR from Trypanosoma cruzi, Leishmania major and Plasmodium vivax) and pteridin reductase (PTR from T. cruzi and L. major) structures. All compounds were in vitro screened against both bloodstream trypomastigotes of T. cruzi (NINOA and INC-5 strains) and promatigotes of Leishmania mexicana (MHOM/BZ/61/M379 strain), and also for cytotoxicity using Vero cell line. Against T. cruzi, three compounds (5, 6 and 8) were the most effective showing a better activity profile than nifurtimox and benznidazole (reference drugs). Against L. mexicana, four compounds (5, 6, 8, and 9) exhibited the highest activity, even than glucantime (reference drug). In the cytotoxicity assay, protozoa were more susceptible than Vero cells. In vivo Plasmodium berghei assay (ANKA strain), the compounds 1, 5, 6 and 8 showed a more comparable activity than chloroquine and pyrimethamine (reference drugs) when they were administrated by the oral route. The antiprotozoal activity of these substances, endowed with redox properties, represented a good starting point for a medicinal chemistry program aiming for chemotherapy of Chagas' disease, leishmaniosis and malaria. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 96. DOI:10.1016/j.ejmech.2015.04.028
  • Source
    European Journal of Medicinal Chemistry 05/2015; 96. DOI:10.1016/j.ejmech.2015.04.029
  • [Show abstract] [Hide abstract]
    ABSTRACT: A key challenge in anticancer therapy is to gain control over the biodistribution of cytotoxic drugs. The most promising strategy consists in conjugating drugs to tumor-targeting carriers, thereby combining high cytotoxic activity and specific delivery. To target Gb3-positive cancer cells, we exploit the non-toxic B-subunit of Shiga toxin (STxB). Here, we have conjugated STxB to highly potent auristatin derivatives (MMA). A former linker was optimized to ensure proper drug-release upon reaching reducing environments in target cells, followed by a self-immolation step. Two conjugates were successfully obtained, and in vitro assays demonstrated the potential of this targeting system for the selective elimination of Gb3-positive tumors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.047
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel series of 3,4-diaza-bicyclo[4.1.0]hept-4-en-2-ones were designed and synthesized as H3R analogs of irdabisant 6. Separation of the isomers, assignment of the stereochemistry by crystallography, and detailed profiling of diastereomers 25 and 26 led to the identification of (1R,6S)-5-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)propoxy]phenyl}-3,4-diaza-bicyclo[4.1.0]hept-4-en-2-one 25 as a potential second generation H3R candidate. Diastereomer 25 had high H3R binding affinity, excellent selectivity, displayed potent H3R functional antagonism and robust wake-promoting activity in vivo, and showed acceptable pharmacokinetic and pharmaceutical profiles for potential further development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.054
  • [Show abstract] [Hide abstract]
    ABSTRACT: Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound 1, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.055
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of novel ursolic acid (UA) derivatives modified at the C-3 and the C-28 positions were designed and synthesized in an attempt to develop potential antitumor agents. The in vitro cytotoxicity were evaluated against five cancer cell lines (MGC-803, HCT-116, T24, HepG2 and A549 cell lines) and a normal cell (HL-7702) by MTT assay. The screening results indicated that some of these target compounds displayed moderate to high levels of antiproliferative activities compared with ursolic acid and 5-fluorouracil (5-FU), and exhibited much lower cytotoxicity than 5-FU, indicating that the targeted compounds had selective and significant effect on the cell lines. The induction of apoptosis and affects on the cell cycle distribution of compound 6r were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which revealed that the antitumor activity of 6r was possibly achieved through the induction of cell apoptosis by G1 cell-cycle arrest. Western blot and qRT-PCR (quantitative real-time PCR) experiments demonstrated that compound 6r may induce apoptosis through both of intrinsic and extrinsic apoptosis pathway. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.051
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fifteen 8-substituted-phenyl-6-ferrocenyl-4-methyl-2H-pyrano[3,2-g]quinolin-2-ones were synthesized via Povarov three-component reaction, in which the substituted aromatic aldehydes reacted with ferrocenylacetylene and 7-amino-4-methylcoumarin in the presence of Ce(OTf)3 as the catalyst. The obtained coumarin-fused quinolines were applied to quench 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and to inhibit 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. It was found that the ferrocenyl group attaching to pyrano[3,2-g]quinolin-2-one scaffold can trap radicals and inhibit DNA oxidation even in the absence of phenolic hydroxyl group. The inhibitory effects on radicals and DNA oxidation can be further enhanced by the electron-donating groups such as p-(N,N-dimethyl amino)phenyl, ferrocenyl, and furan-2-yl group at 8-position. Therefore, ferrocenyl-substituted pyrano[3,2-g]quinolin-2-one skeleton together with electron-donating groups became a novel structural style for antioxidants. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.061
  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify novel multi-target-directed drug candidates for the treatment of cancer, a series of benzoselenazole-stilbene hybrids were synthesised by combining the pharmacophores of resveratrol and ebselen. The biological assay indicated that all of the hybrids exhibited antiproliferative activities against four human cancer cell lines and demonstrated good TrxR inhibitory activities. The mechanism of cell apoptosis was investigated in G2/M cell cycle arrest induced by compound 6e and the apoptosis of the human liver carcinoma Bel-7402 cell line. The significant increase in intracellular ROS confirmed that compound 6e was capable of causing oxidative stress-induced apoptosis in cancer cells. Our results support the potential of compound 6e as a candidate for further studies examining the development of novel drugs for cancer treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.030
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, A3G) is a potent restriction factor against human immunodeficiency virus type 1 (HIV-1) by inducing hypermutation of G to A in viral genome after its incorporation into virions. HIV-1 Vif (Virion Infectivity Factor) counteracts A3G by inducing ubiquitination and proteasomal degradation of A3G protein. Vif-A3G axis therefore is a promising therapeutic target of HIV-1. Here we report the screening, synthesis and SAR studies of benzimidazole derivatives as potent inhibitors against HIV-1 replication via protecting A3G protein. Based on the steep SAR of the benzimidazole scaffold, we identified compound 14 and 26 which provided the best potency, with IC50 values of 3.45 nM and 58.03 nM respectively in the anti-HIV-1 replication assay in H9 cells. Compound 14 and 26 also afforded protective effects on A3G protein level. Both compounds have been proved to be safe in acute toxicological studies. Taken together, we suggest that these two benzimidazole derivatives can be further developed as a new category of anti-HIV-1 leads. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.050
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of celastrol derivatives as potential telomerase inhibitors were designed and synthesized. The bioassays demonstrated that title compounds displayed potent anticancer activities against SGC-7901, SMMC-7721, MGC-803 and HepG-2 cell lines, among them, compounds 3c and 3d which containing hydrophilicity moieties exhibited high anti-proliferative activities (IC50 = 0.10-1.22 μM). The preliminary mechanism of antitumor action indicated that title compound 3c could induce significant SMMC-7721 cells apoptosis. A modified TRAP assay showed that compounds 3c and 3d displayed the most potent inhibitory activity with IC50 values at 0.11 and 0.34 μM, respectively. And there was a good correlation between telomerase inhibition and anti-proliferative inhibition of SMMC-7721 cells. Moreover, molecular docking indicated that the active compound 3c was nicely bound into the telomerase hTERT active site, hydrophobic, van der Waals and two hydrogen bond interactions with conserved residues ASP 628 and TYR 949 were found. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.039
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of 2, 6-disubstituted pyridazinone derivatives were evaluated and optimized for their c-Met inhibitory activity in enzyme and cellular assay. An analysis of the SAR results arising from computer modeling analysis of members of the library led to the proposal that in order to obtain optimal inhibitory activity in cellular systems the lipophilic/hydrophilic properties of individual structural fragments in the inhibitors need to match those of corresponding binding pockets in the enzyme. Guided by this proposal, the quinoline-pyridazinone 8a, containing hydrophobic 6-indolyl pyridazinone and quinoline moieties along with a hydrophilic morpholine terminal group, was designed and synthesized. The results of studies with this substance showed that it is a selective c-Met inhibitor with both a high enzyme inhibition IC50 value of 4.2 nM and a high EBC-1 cell proliferation inhibition IC50 value of 17 nM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.041
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the synthesized derivatives showed effective anti-HBV activity. Of these compounds, compound 4c-1 showed the most potent anti-HBV activity, demonstrating potent inhibitory effect not only on the secretion of HBsAg (IC50 = 14.18 μM, SI = 17.85) and HBeAg (IC50 = 6.20 μM, SI = 40.82) secretion but also HBV DNA replication (IC50 = 23.43 μM, SI = 10.80). The structure-activity relationships (SARs) of phenylpropanoid derivatives had been discussed, which were useful for phenylpropanoid derivatives to be explored and developed as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site were carried out to explore the molecular interactions and a molecular target for activity of phenylpropanoid derivatives with the protein using a moe-docking technique. This study identified a new class of potent anti-HBV agents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.056
  • [Show abstract] [Hide abstract]
    ABSTRACT: In response to the extensive use of antibiotics, bacteria have evolved numerous mechanisms of defense against antimicrobial agents. Among them, extrusion of the antimicrobial agents outside the bacterial cell through efflux pumps is a major cause of concern. At first limited to one or few structurally-related antibiotics, bacterial resistance have then progressed towards cross-resistance between different classes of antibiotics, leading to multidrug-resistant microorganisms. Emergence of these pathogens requires development of novel therapeutic strategies and inhibition of efflux pumps appears to be a promising strategy that could restore the potency of existing antibiotics. NorA is the most studied chromosomal efflux pump of Staphylococcus aureus; it is known to be implied in resistance of Methicillin-resistant S. aureus (MRSA) strains against a wide range of unrelated substrates, including hydrophilic fluoroquinolones. Starting from 6-benzyloxypyridine-3-boronic acid I that we previously identified as a potential inhibitor of the NorA efflux pump against the NorA-overexpressing S. aureus 1199B strain (SA1199B), we describe here the synthesis and biological evaluation of a series of 6-(aryl)alkoxypyridine-3-boronic acids. 6-(3-Phenylpropoxy)pyridine-3-boronic acid 3i and 6-(4-phenylbutoxy)pyridine-3-boronic acid 3j were found to potentiate ciprofloxacin activity by a 4-fold increase compared to the parent compound I. In addition, it has been shown that both compounds promote Ethidium Bromide (EtBr) accumulation in SA1199B, thus corroborating their potential mode of action as NorA inhibitors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.02.056
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of novel heterocycle-modified betulinic acid (BA) derivatives were synthesized and investigated for their activity against the growth of eight non-drug resistant and one multidrug-resistant tumor cell line using a sulforhodamine B (SRB) assay. The most active compound 17 showed an average IC50 1.19 μM, which was about 20 times more potent than the lead compound BA. It is amazing that for most synthetic saturated N-heterocycle derivatives, MCF-7/ADR was the most sensitive tumor cells, especially 17 showed the most potent antitumor activity (IC50 = 0.33 μM) on this multidrug-resistant tumor cell line, that was 117 times more potent than BA. Most of the tested compounds displayed less toxic on human fibroblasts (HAF) in comparison with the tumor cell lines. The cytometry and transwell migration assays were used to test the ability of 17 to induce apoptosis and inhibit metastasis on tumor cell lines respectively. Copyright © 2015. Published by Elsevier Masson SAS.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.048
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several phenylethanoid glycoside derivatives were designed and synthesized. Most of the synthetic compounds showed significant neuroprotective effects, including antioxidative and anti-apoptotic properties. Specifically, target compounds displayed potent effects against various toxicities such as H2O2 and 6-hydroxydopamine (6-OHDA) in PC12 cells. Among the synthetic derivatives, three compounds (5, 6, 8) exhibited much superior activities to the marketed drug Edaravone. The compounds were able to prevent the 6-OHDA-induced damage in PC12 cells in a dose-dependent manner. The anti-apoptotic effects could be observed via cell morphological changes. Moreover, the compounds significantly reduced the intracellular ROS increase resulting from 6-OHDA treatment. The preliminary structure-activity relationships were also explored. Compounds 5, 6, 8 may hold the potential as promising neuroprotective agents and new lead compounds for the treatment of neurodegenerative diseases or cerebral ischemia. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 05/2015; 95. DOI:10.1016/j.ejmech.2015.03.038