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 proliferation in vitro by targeting pantothenate utilization. To inform the design of next generation analogues, we set out to synthesize and test a series of synthetic enamide-bearing pantothenate analogues. We demonstrate that conservation of the R-pantoyl moiety and the trans-substituted double bond of CJ-15,801 is important for the selective, on-target antiplasmodial effect, while replacement of the carboxyl group is permitted, and, in one case, favored. Additionally, we show that the antiplasmodial potency of CJ-15,801 analogues that retain the R-pantoyl and trans-substituted enamide moieties correlates with inhibition of P. falciparum pantothenate kinase (PfPanK)-catalyzed pantothenate phosphorylation, implicating the interaction with PfPanK as a key determinant of antiplasmodial activity.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Spry C,Sewell AL,Hering Y,Villa MVJ,Weber J,Hobson SJ,Harnor SJ,Gul S,Marquez R,Saliba KJdoi
10.1016/j.ejmech.2017.08.050subject
Has Abstractpub_date
2018-01-01 00:00:00pages
1139-1147eissn
0223-5234issn
1768-3254pii
S0223-5234(17)30661-Xjournal_volume
143pub_type
杂志文章abstract::The estrogenic/antiestrogenic activity and the genotoxicity/antigenotoxicity of bee pollen from Salix alba L. and Cystus incanus L. and its derivative extracts in yeast and human cells was investigated. All samples showed a marked inhibitory effect on the activity of the natural estrogen 17 beta-estradiol (higher than...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2010.06.001
更新日期:2010-09-01 00:00:00
abstract::Discovery of novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Cajaninstilbene acid, which is isolated from pigeonpea leaves, has shown antibacterial activity. In this study, a series of cajaninstilbene acid derivatives were designed and synthesized. The a...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.06.008
更新日期:2015-07-15 00:00:00
abstract::A small library of coumarins, carrying butynyl-amino chains, was synthesized continuing our studies in the field of MDR reverting ageEnts and in order to obtain multipotent agents to combat malignancies. In particular, the reported anticancer and chemopreventive natural product 7-isopentenyloxycoumarin was linked to d...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.01.020
更新日期:2017-02-15 00:00:00
abstract::Designing covalent allosteric modulators brings new opportunities to the field of drug discovery towards G-protein-coupled receptors (GPCRs). Targeting an allosteric binding pocket can allow a modulator to have protein subtype selectivity and low drug resistance. Utilizing covalent warheads further enables the modulat...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2020.112690
更新日期:2020-11-15 00:00:00
abstract::A series of 4H-1,2,3-thiadiazolo[5,4-b]indoles were synthesized by novel tandem of oxidative cyclization of 3-alkoxycarbonylhydrazonoindoline-2-thiones, 1,5-H-shift and elimination of tert-butoxy(ethoxy)carbonyl group. The simple method for their modifications by the reactions with electrophilic agents were elaborated...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.11.011
更新日期:2016-01-27 00:00:00
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
doi:10.1016/j.ejmech.2019.02.019
更新日期:2019-04-15 00:00:00
abstract::A series of novel 4-aryl-pyrido[1,2-c]pyrimidine derivatives containing a 1-(2-quinoline)piperazine moiety was synthesized. The chemical structure of new compounds was confirmed by FT-IR, (1)H NMR, (13)C NMR and HRMS spectra as well as elemental analysis. Affinity of the novel pyrido[1,2-c]pyrimidine derivatives for 5...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.05.003
更新日期:2015-06-15 00:00:00
abstract::We described in this article the very efficient 2,6-cis ou 2,4,6-cis diastereoselective synthesis (2 or 3 steps, 62-65% global yields) from Prins-cyclization reaction as synthetic key-step to tetrahydropyran rings construction of 10 new congeners compounds (3-12) designed from Naproxen structure. These tetrahydropyran...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.09.046
更新日期:2012-12-01 00:00:00
abstract::Computational drug repositioning is of growing interest to academia and industry, for its ability to rapidly screen a huge number of candidates in silico (exploiting comprehensive drug datasets) together with reduced development cost and time. The potential of drug repositioning has not been fully evaluated yet for cy...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2021.113186
更新日期:2021-01-13 00:00:00
abstract::Frequency of tuberculosis and malaria is progressively increasing worldwide. New emerging strain of bacterium and resistance to currently available drugs make this field more conscientious and alarming. In this connection a series of substituted quinolinyl chalcones and substituted quinolinyl pyrimidines were synthesi...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.10.011
更新日期:2009-05-01 00:00:00
abstract::A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different t...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.01.051
更新日期:2016-03-23 00:00:00
abstract::We have synthetised a series of oxidised apomorphine derivatives (orto and para quinones 2-5), in order to analyse their vascular activity. We have performed radioligand binding assays on rat cortical membranes and functional studies on rat aortic rings. Instead the relaxant activity exhibited by (R)-apomorphine, o-qu...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(03)00057-6
更新日期:2003-05-01 00:00:00
abstract::A series of 9-bromo-substituted indolizinoquinoline-5,12-dione derivatives was synthesized. Antimicrobial activity assessment indicates that compounds 1, 26, 27 and 28 exhibit strong activity against gram-positive bacterial strains, including Beta-hemolytic streptococcus CMCC32210, Staphylococcus aureus ATCC25923, Sta...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.07.042
更新日期:2011-09-01 00:00:00
abstract::Staphylococcus aureus (S. aureus) is responsible for difficult-to-treat and relapsing infections and constitutes one of the most problematic pathogens due to its multiple resistances to clinically available antibiotics. Additionally, the ability of S. aureus to develop small-colony variants is associated with a reduce...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.11.019
更新日期:2014-06-10 00:00:00
abstract::A new series of chiral 1,3,4-thiadiazoles derivatives possessing gamma-substituted butenolide moiety were synthesized and evaluated for in vitro anticancer properties. All the compounds showed good anticancer activities against Hela cell lines. Of all the studied compounds, compound 9e exhibited the best inhibitory ac...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.03.023
更新日期:2009-08-01 00:00:00
abstract::The present studies reports the synthesis of hydoxylated thymol analogues (4a-e) and (6a-c) as mushroom tyrosinase inhibitors. The title compounds were obtained in good yield and characterized by FTIR, (1)H NMR, (13)C NMR, Mass spectral data and X-ray crystallography in case of compound (6a). The inhibitory effects on...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.05.031
更新日期:2015-06-15 00:00:00
abstract::Targeting epigenetic dysregulation has emerged as a valuable therapeutic strategy in cancer treatment. Especially epigenetic combination therapy of histone deacetylase inhibitors (HDACi) with established anti-cancer drugs has provided promising results in preclinical and clinical studies. The structural optimization o...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2020.113095
更新日期:2021-02-05 00:00:00
abstract::Synthesis of a new series of diarylureas and diarylamides possessing 4-aryl-8-amino(acetamido)quinoline scaffold is described. Their in vitro antiproliferative activities against ten melanoma cell lines were tested. Compounds 1l, 2l, 3c, and 4c showed the highest potency against A375P cell line with IC50 values in sub...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.06.060
更新日期:2013-01-01 00:00:00
abstract::A series of 2'-aryl/benzyl-2-aryl-4-methyl-4',5-bithiazolyl derivatives, 25-64 were synthesized and evaluated for inhibitory activity against Mycobacterium smegmatis MC(2) 155 strain and antimicrobial activities against four pathogenic bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Proteus vul...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.03.016
更新日期:2015-04-13 00:00:00
abstract::A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines (9a-b), as monoamine oxidase inhibitors (MAOIs...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.02.039
更新日期:2015-03-26 00:00:00
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
doi:10.1016/j.ejmech.2007.03.002
更新日期:2008-01-01 00:00:00
abstract::Since pyrithiobac (PTB) is a successful commercial herbicide with very low toxicity against mammals, it is worth exploring its derivatives for an extensive study. Herein, a total of 35 novel compounds were chemically synthesized and single crystal of 6-6 was obtained to confirm the molecular structure of this family o...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.02.002
更新日期:2019-04-01 00:00:00
abstract::Selective COX-2 inhibitors have attracted much attention in recent times in the design of non-steroidal anti-inflammatory agents (NSAID), which are devoid of the common side effects of classical NSAIDs. QSAR studies have been performed on a series of diaryl furanones that acts as selective COX-2 inhibitor using Molecu...
journal_title:European journal of medicinal chemistry
pub_type: 更正并重新发布的文章,杂志文章
doi:10.1016/j.ejmech.2004.06.005
更新日期:2004-10-01 00:00:00
abstract::In the present paper, a fast and automated method for the synthesis of (13)N-labelled azo compounds is reported for the first time. The labelling strategy is based on trapping [(13)N]NO(2)(-) in an anion exchange resin. The reaction with primary aromatic amines in acidic media led to the formation of the corresponding...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2010.08.053
更新日期:2010-11-01 00:00:00
abstract::The synthesis of 7α-testosterone-chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7α-allyltesto...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.04.027
更新日期:2013-06-01 00:00:00
abstract::In an attempt to develop effective and safe anticancer agents, we designed, synthesized and examined 23 novel quinacrine (QC) derivatives by combining the 9-aminoacridine scaffold and the [1,3]thiazinan-4-ones group. Most of these hybrids showed strong anticancer activities, among which 3-(3-(6-chloro-2-methoxyacridin...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.11.097
更新日期:2018-01-01 00:00:00
abstract::Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are the current focus on the indication for the management of hyperglycemia in diabetes. Here, a novel series of C-linked indolylxyloside-based inhibitors of SGLT2 has been discovered. Structure-activity relationship studies revealed that substituents at the...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.06.053
更新日期:2012-09-01 00:00:00
abstract::Polyether ionophore antibiotics (ionophores) represent a large group of more than 120 lipid-soluble compounds that are widely used in veterinary medicine because of their significant antimicrobial activity. In addition to the industrial use of ionophores, some of them effectively and selectively inhibit properties of ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2019.01.034
更新日期:2019-03-15 00:00:00
abstract::A series of 3- and 5-methylthiophene-2-carboxaldehyde alpha-(N)-heterocyclichydrazones were synthesized and submitted to an in vitro investigation of their anticancer, anti-HIV and antimicrobial activities. Some of the newly synthesized compounds were found to possess antiproliferative properties, whereas no anti-HIV ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2003.09.012
更新日期:2004-02-01 00:00:00
abstract::In our search for new compounds acting on benzodiazepine receptors among the fused 2-thiohydantoin derivatives, a series of arylidene imidazo[2,1-b]thiazines was synthesized. The 1,2- and 2,3- cyclized derivatives of mono- and di-substituted Z-5-arylidene-2-thiohydantoins were examined (the X-ray crystal structure of ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(01)01239-9
更新日期:2001-05-01 00:00:00