Abstract:
:Members of the GATA family of transcription factors are zinc finger proteins that were shown to play evolutionary conserved roles in cell differentiation and proliferation in different organisms. We hypothesized that by finding new molecules that inhibit their function to be crucial in future therapeutical interventions for various diseases. By virtual high throughput screening using a version of glide (Schrodinger®) program with both crystal and NMR structure of GATA C-terminal zinc finger, we identified new small molecular weight chemicals with lead-like properties. We used in vitro cell-based assays to show that these molecules selectively and efficiently inhibit GATA4 activity by inhibiting its interaction with the DNA. In addition we showed that these molecules can block the activation of downstream target genes by GATA4. Moreover these compounds can moderately enhanced a mouse model of myoblast differentiation into myotubes. This might be partially due to decreased GATA4/DNA interaction as shown by gel retardation assays. Further investigation is needed to reach selectivity and efficacy. Our study however do show that in silico screening combined with in vitro studies are efficient tools to unravel new molecules that interact with zinc finger proteins such as GATA4.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
El-Hachem N,Nemer Gdoi
10.1016/j.bmc.2011.01.022subject
Has Abstractpub_date
2011-03-01 00:00:00pages
1734-42issue
5eissn
0968-0896issn
1464-3391pii
S0968-0896(11)00038-1journal_volume
19pub_type
杂志文章abstract::Twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. The amides of manzamine A (1) showed significantly reduced cytotoxicity against Vero cells, although were less active than 1. The structure-activity analysis showed that linear, short alkyl groups adjacent to...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.09.026
更新日期:2009-11-15 00:00:00
abstract::We herein report the anti-inflammatory activity of some newly synthesized heterocyclic pyridone and pyridine derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All compounds, except 3b, 22, and 23, were interestingly less toxic t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.02.045
更新日期:2006-07-01 00:00:00
abstract::Design and synthesis of an EP2-receptor selective agonist began with the chemical modification of alpha- and omega-chains of butaprost 1a, which exhibits an affinity for the IP-receptor. Two series of prostaglandin (PG) analogues with a 16-hydroxy-17,17-trimethylene moiety as an omega-chain were identified. Among thos...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00369-8
更新日期:2002-04-01 00:00:00
abstract::The synthesis and structure-activity relationship of a new class of indole derivatives with low-nanomolar affinity for the SERT and high selectivity versus the 5-HT1A receptor were recently reported. Based on their chemical structure, four new indolylpropylamine derivatives which contain atoms to afford future labelin...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.05.006
更新日期:2008-06-15 00:00:00
abstract::This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.10.022
更新日期:2012-01-01 00:00:00
abstract::Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable chemical and thermal stability, and hydrophobic character. These features may allow application of carboranes as a new hydrophobic core structure in biologically active molecules that interact...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.06.061
更新日期:2005-12-01 00:00:00
abstract::Several studies have demonstrated that N-substituted amino acid derivatives exhibit weak anticonvulsant activities in vivo. In the present study, a series of amides of aminoacids structurally related to aminoacetamide have been synthesised and investigated for anticonvulsant activity. Among the molecules investigated,...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.12.064
更新日期:2006-05-15 00:00:00
abstract::Thymidylate synthase (TS) (EC 2.1.1.45), an enzyme involved in the DNA synthesis of both prokaryotic and eukaryotic cells, is a potential target for the development of anticancer and antinfective agents. Recently, we described a series of phthalein and naphthalein derivatives as TS inhibitors. These compounds have str...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00541-2
更新日期:2003-03-20 00:00:00
abstract::A novel artificial peptide named HPH-Pep, comprising a pyridine and two histidine units, was synthesized. The HPH-Pep-CuII complex had unique pentacoordinated structure as shown by X-ray crystallography and exhibited superoxide-scavenging activity as indicated by ESR spectroscopy. The superoxide-quenching profile of H...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(96)00161-7
更新日期:1996-10-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.03.050
更新日期:2009-05-01 00:00:00
abstract::The farnesoid X receptor (FXR) belonging to the metabolic subfamily of nuclear receptors is a ligand-induced transcriptional activator. Its central function is the physiological maintenance of bile acid homeostasis including the regulation of glucose and lipid metabolism. Accessible structural information about its li...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.09.039
更新日期:2011-11-15 00:00:00
abstract::Three new derivatives of 2-substituted 1,3,4-thiadiazole-5-sulfonamide have been synthesized. These compounds are 2-(3-chloropropionylamino)-1,3,4-thiadiazole-5-sulfonamide (1); 2-(2,2-dichloroacetylamino)-1,3,4-thiadiazole-5-sulfonamide (2); and 2-(3-phenylpropionylamino)-1,3,4-thiadiazole-5-sulfonamide (3). Inhibiti...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(96)00272-6
更新日期:1997-03-01 00:00:00
abstract::Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential thera...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.09.010
更新日期:2013-11-15 00:00:00
abstract::Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.01.010
更新日期:2018-05-01 00:00:00
abstract::Silica sulfuric acid catalyzes efficiently the reaction of sulfonamides with both carboxylic acid anhydrides and chlorides under solvent-free and heterogeneous conditions. All the reactions were done at room temperature and the N-acylsulfonamides were obtained with high yields and purity via an easy work-up procedure....
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.04.011
更新日期:2008-05-15 00:00:00
abstract::Enzymes catalyzing the biosynthesis of bacterial peptidoglycan represent traditionally a collection of highly selective targets for novel antibacterial drug design. Four members of the bacterial Mur ligase family-MurC, MurD, MurE and MurF-are involved in the intracellular steps of peptidoglycan biosynthesis, catalyzin...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.05.058
更新日期:2014-08-01 00:00:00
abstract::Janus kinases (JAKs) are considered promising targets for the treatment of autoimmune diseases including rheumatoid arthritis (RA) due to their important role in multiple cytokine receptor signaling pathways. Recently, several JAK inhibitors have been developed for the treatment of RA. Here, we describe the identifica...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2018.08.005
更新日期:2018-10-01 00:00:00
abstract::A water soluble derivative (2) of topopyrones was selected for NMR studies directed to elucidate the mode of binding with specific oligonucleotides. Topopyrone 2 can intercalate into the CG base pairs, but the residence time into the double helix is very short and a fast chemical exchange averaging occurs at room temp...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.12.005
更新日期:2009-01-15 00:00:00
abstract::Bilirubin, biliverdin and their serum albumin complexes were tested as oxyradical scavengers (superoxide generated by the xanthine/xanthine oxidase system and peroxyl radical-trapping antioxidant ability). As superoxide scavengers the free bile pigments showed activities near to that of serum albumin, higher than the ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)82013-1
更新日期:1994-03-01 00:00:00
abstract::During the course of a collaborative screening program, a set of 1-phenyl-4-pyridyl-butadienes was found to exhibit in vitro activity against Eimeria tenella in a cell-based assay. Activity was dependent on the chain length and degree of unsaturation of the linker between the two aryl groups as well as substitution of...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(03)00330-4
更新日期:2003-09-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2019.03.024
更新日期:2019-04-15 00:00:00
abstract::P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.05.031
更新日期:2017-07-15 00:00:00
abstract::Reaction of γ-Boc-GABA, prepared by protecting the γ-amino moiety of the amino butyric acid with the tert-butyloxycarbonyl (Boc) protecting group, with 4-methyl/ethyl benzenesulfonamide, followed by removal of the Boc protecting group in 3 M HCl afforded the corresponding hydrochlorides, which were further derivatized...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.10.041
更新日期:2014-12-15 00:00:00
abstract::To elucidate the structure-activity relationships of metabolites of folates as antioxidants, the O-H bond dissociation enthalpies (BDEs) and ionization potentials (IPs) for these compounds were calculated by density functional theory (DFT) on B3LYP/6-31+G(,3pd) level. Accordingly, the antioxidant activity difference f...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2004.11.047
更新日期:2005-02-15 00:00:00
abstract::Isoflavones are bioactive compounds that have been shown to decrease lipid accumulation in vitro. However, the knowledge of the isoflavone formononetin is limited. The aim of the study was to assess the effects of formononetin and its two synthetic analogues, 2-(2-bromophenyl)-formononetin and 2-heptyl-formononetin, o...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.08.037
更新日期:2014-11-01 00:00:00
abstract::New 7-aryl or 7-heteroarylamino-2,3-dimethylbenzo[b]thiophenes were prepared by palladium-catalyzed Buchwald-Hartwig cross-coupling of 7-bromo or 7-amino-2,3-dimethylbenzo[b]thiophenes, previously prepared by us, with substituted (4-methoxy or 3,4-dimethoxy) anilines and 3-aminopyridine or with substituted (3-methoxy ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.11.035
更新日期:2007-02-15 00:00:00
abstract::Various 4-(anilino)pyrrole-2-carboxamides were designed and synthesized as novel androgen receptor (AR) antagonists without steroidal or anilide structure, based on our strategy for developing full antagonists of nuclear receptors. Introduction of a bulky N-alkyl group, such as a cyclohexylmethyl or benzyl group, incr...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.05.063
更新日期:2008-07-15 00:00:00
abstract::In order to increase metabolic stability and water solubility of arenastatin A, an extremely potent cytotoxic depsipeptide from the Okinawan marine sponge of Dysidea arenaria, several 15,20-triamide analogues with a polar substituent on the phenyl ring were synthesized. The 15,20-triamide analogues with a polar substi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.07.019
更新日期:2006-11-15 00:00:00
abstract::Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical balance between ceramide and sphingosine-1-phosphate. Much effort has been dedicated to develop inhibitors against these enzymes. Naturally occurring pachastrissamine (jaspine B) and all its stereoisomers were prepared and evaluated for their...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.07.061
更新日期:2011-09-15 00:00:00
abstract::A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2017.03.055
更新日期:2017-05-15 00:00:00