Abstract:
:Given the worldwide spread of bacterial drug resistance, there is an urgent need to develop new compounds that exhibit potent antibacterial activity and that are unimpaired by this phenomenon. Quaternary ammonium compounds have been used for many years as disinfectants, but recent advances have shown that polycationic derivatives exhibit much stronger activity and are less prone to bacterial resistance than commonly used monocationic compounds. In this sense, we prepared three series of new bis-cationic compounds: bis-thiazoliums, bis-imidazoliums, and bis-1,2,4-triazoliums. If some compounds of the first series showed fair antibacterial activity, most of those belonging to the two other series were highly potent, with minimum inhibitory concentrations close to 1 μg mL-1 . Some of them also exhibited low toxicity toward eukaryotic MRC-5 lung fibroblasts, and we showed that this toxicity is clearly correlated with clogP. Finally, four selected compounds were found to exhibit a clear bactericidal effect.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Thomas B,Duval RE,Fontanay S,Varbanov M,Boisbrun Mdoi
10.1002/cmdc.201900151subject
Has Abstractpub_date
2019-07-03 00:00:00pages
1232-1237issue
13eissn
1860-7179issn
1860-7187journal_volume
14pub_type
杂志文章相关文献
ChemMedChem文献大全abstract::The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000050
更新日期:2010-06-07 00:00:00
abstract::Apelin is the endogenous ligand of the APJ receptor, a member of the G-protein-coupled receptor family. The apelin-APJ complex has been detected in many tissues and is emerging as a promising target for several pathophysiological conditions. There is currently little information on the structure-activity relationship ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100492
更新日期:2012-02-06 00:00:00
abstract::Serine- and metallo-β-lactamases present a threat to the clinical use of nearly all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. Efforts to develop metallo-β-lactamase (MBL) inhibitors require suitable screening platforms to allow the rapid determination of β-lactamase activity and eff...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300350
更新日期:2013-12-01 00:00:00
abstract::Indanesulfonamides are interesting lead compounds for designing selective inhibitors of the different isoforms of the zinc enzyme Carbonic Anhydrase (CA). Herein, we report for the first time the X-ray crystal structure of two such derivatives, namely indane-5-sulfonamide and indane-2-valproylamido-5-sulfonamide, in c...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700274
更新日期:2008-03-01 00:00:00
abstract::N-Acylethanolamine acid amidase (NAAA) is a cysteine amidase that preferentially hydrolyzes saturated or monounsaturated fatty acid ethanolamides (FAEs), such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are endogenous agonists of nuclear peroxisome proliferator-activated receptor-α (PPAR-α). Com...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300416
更新日期:2014-02-01 00:00:00
abstract::Human equilibrative nucleoside transporter 1 (hENT1) is a prototypical nucleoside transporter protein ubiquitously expressed on the cell surface of almost all human tissue. Given the role of hENT1 in the transport of nucleoside drugs, an important class of therapeutics in the treatment of various cancers and viral inf...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402047
更新日期:2014-09-01 00:00:00
abstract::We previously found that p97 ATPase inhibitors 2-(2-amino-1H-benzo[d]imidazol-1-yl)-N-benzyl-8-methoxyquinazolin-4-amine (ML240) and 2-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine (ML241) specifically target the D2 domain of wild-type p97. In addition, one of the major p97 cofactors,...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402420
更新日期:2015-01-01 00:00:00
abstract::Chemical biology approaches have a long history in the exploration of the G-protein-coupled receptor (GPCR) family, which represents the largest and most important group of targets for therapeutics. The analysis of the human genome revealed a significant number of new members with unknown physiological function which ...
journal_title:ChemMedChem
pub_type: 历史文章,杂志文章,评审
doi:10.1002/cmdc.200600134
更新日期:2006-08-01 00:00:00
abstract::Greater than the sum of its parts: Artemisinins are currently in phase I-II clinical trials against breast, colorectal and non-small-cell lung cancers. In an attempt to offer increased specificity, a series of hybrid artemisinin-polypyrrole minor groove binder conjugates are described. DNA binding/modelling studies an...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200536
更新日期:2013-05-01 00:00:00
abstract::Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin-derived compounds, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), in an attempt to...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000482
更新日期:2011-03-07 00:00:00
abstract::Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and i...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000122
更新日期:2020-06-04 00:00:00
abstract::Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kina...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.200600271
更新日期:2007-08-01 00:00:00
abstract::A novel class of isochroman dopamine analogues, originally reported by Abbott Laboratories, have >100-fold selectivity for D₁-like over D₂-like receptors. We synthesized a parallel series of chroman compounds and showed that repositioning the oxygen atom in the heterocyclic ring decreases potency and confers D₂-like r...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100010
更新日期:2011-06-06 00:00:00
abstract::Detailed information on the metabolic fate of lead compounds can be a powerful tool for an informed approach to the stabilization of metabolically labile compounds in the lead optimization phase. The combination of high performance liquid chromatography (HPLC) with nuclear magnetic resonance (NMR) spectroscopy and mas...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700203
更新日期:2008-01-01 00:00:00
abstract::Some hybrid foldamers of various length, all containing the (4R,5S)-4-carboxy-5-methyloxazolidin-2-one (d-Oxd) moiety alternating with an l-amino acid (l-Val, l-Lys, or l-Ala), were prepared in order to study their preferred conformations and to evaluate their biological activity. Surprisingly, only the longer oligome...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600597
更新日期:2017-02-20 00:00:00
abstract::The histone methyltransferase SET7/9 methylates not only histone but also non-histone proteins as substrates, and therefore, SET7/9 inhibitors are considered candidates for the treatment of diseases. Previously, our group identified cyproheptadine, used clinically as a serotonin receptor antagonist and histamine recep...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800233
更新日期:2018-08-10 00:00:00
abstract::Cellular chaperones that belong to the heat-shock protein 90 (Hsp90) family are a prerequisite for successful viral propagation for most viruses. The hepatitis C virus (HCV) uses Hsp90 for maturation, folding, and modification of viral proteins. Based on our previous discovery that marine alkaloid analogues with a 4,5...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800724
更新日期:2019-02-05 00:00:00
abstract::Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology. Potent, selective, brain-penetrant inhibitors of Plk-2 were obtained from a structure-guided drug discovery approach...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300166
更新日期:2013-08-01 00:00:00
abstract::Schistosomiasis is a neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy relies on mass treatment with only one drug: praziquantel. Based on the 3-chlorobenzothiophene-2-hydroxamic acid J1075, a series of hydroxamic acids with different scaffolds were prep...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800238
更新日期:2018-08-10 00:00:00
abstract::Vascular endothelial growth factor receptor 2 (VEGFR2) has been proven to play a major role in the regulation of tumor angiogenesis. A series of novel glycyrrhetic acid derivatives were synthesized and evaluated for their VEGFR2 inhibitory activity as well as their antiproliferative properties against four cancer cell...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700271
更新日期:2017-07-06 00:00:00
abstract::The less polar π-surface of protein amide groups is exposed in many receptor binding sites, either as part of the backbone or in Gln/Asn side chains. Using quantum chemical calculations and Protein Data Bank (PDB) searches on model systems, we investigate the energetics and geometric preferences for the stacking on am...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200512
更新日期:2013-03-01 00:00:00
abstract::Meridional rhodium(III) polypyridyl complexes of the type mer-[RhX(3)(DMSO)(pp)] (X=Cl, pp=phen 1, dpq 2, dppz 3; X=Br, pp=phen 4) represent a promising class of potent cytostatic agents for the treatment of lymphoma and leukemia. Exposure of their DMSO solutions to light leads to slow isomerization to mixtures of the...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800311
更新日期:2009-02-01 00:00:00
abstract::The concise synthesis and structure-activity relationship (SAR) studies of 3-aroylindoles were carried out in an effort to improve the potency and solubility of anticancer drug candidate BPR0L075 (8) by exploring structure modifications through three regimens: substitution of the B ring, at the N1 position, and of the...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200600125
更新日期:2006-10-01 00:00:00
abstract::Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conj...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402373
更新日期:2015-02-01 00:00:00
abstract::LSD1 is a lysine demethylase highly involved in initiation and development of cancer. To design highly effective covalent inhibitors, a strategy is to fill its large catalytic cleft by designing tranylcypromine (TCP) analogs decorated with long, hindered substituents. We prepared three series of TCP analogs, carrying ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900730
更新日期:2020-04-03 00:00:00
abstract::A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ∼2-4 μg mL(-1) ; 2.55-5.09 μm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ∼1.35-3.70 μm] ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600250
更新日期:2016-09-06 00:00:00
abstract::Herein we describe the optimization of a phenotypic hit against Plasmodium falciparum based on an aminoacetamide scaffold. This led to N-(3-chloro-4-fluorophenyl)-2-methyl-2-{[4-methyl-3-(morpholinosulfonyl)phenyl]amino}propanamide (compound 28) with low-nanomolar activity against the intraerythrocytic stages of the m...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900329
更新日期:2019-07-17 00:00:00
abstract::A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000346
更新日期:2010-11-08 00:00:00
abstract::In atomic force microscopy (AFM) a sharp cantilever tip is used to scan surfaces at the atomic level. One further application is force spectroscopy, in which force-distance curves between binding partners located on the cantilever and substrate surface are determined. This requires specifically immobilized molecules. ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201402165
更新日期:2014-09-01 00:00:00
abstract::Targeting LRH-1: Virtual screening and molecular modeling were used to identify novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic target for breast cancer. Hit compounds were synthesized and biologically assayed, and the preliminary results suggest that raloxifene-based analogues, substitu...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200307
更新日期:2012-11-01 00:00:00