Abstract：
:The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Spicer JA,Miller CK,O'Connor PD,Jose J,Huttunen KM,Jaiswal JK,Denny WA,Akhlaghi H,Browne KA,Trapani JAdoi
10.1016/j.ejmech.2017.05.048subject
Has Abstractpub_date
2017-09-08 00:00:00pages
139-155eissn
0223-5234issn
1768-3254pii
S0223-5234(17)30409-9journal_volume
137pub_type
杂志文章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
doi：10.1016/j.ejmech.2015.12.024
更新日期：2016-01-27 00:00:00
abstract：:Tuberculosis (TB) remains one of the most widespread and leading deadliest diseases, around one-third of the world's population harbor a latent infection by Mycobacterium tuberculosis (MTB), and 5-10% eventually develop an active TB. The emergency of MTB new virulent forms as well as the co-infection between MTB and H...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2018.01.080
更新日期：2018-02-25 00:00:00
abstract：:Taking the rising interest in jasmone structure based fragrant compounds into account it has been decided to take up an attempt to synthesize the new heterocyclic derivatives of this 2,3-disubstituted cyclopentenone, which could be characterized by the ability of interaction with the same receptors with which jasmone ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.07.028
更新日期：2009-07-01 00:00:00
abstract：:2-Styrylchromones, which are relatively scarce in nature, have been reported to possess potent cytotoxicities on KB cell line. Lavendustin A, a metabolite of Streptomyces griseolavendus, has been shown to inhibit a growth of A431 cell line. Accordingly, a series of compounds 3a-g having structural features of styrylch...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2006.04.008
更新日期：2006-08-01 00:00:00
abstract：:The absorption of 111 drug and drug-like compounds was evaluated from 111 references based on the ratio of urinary excretion of drugs following oral and intravenous administration to intact rats and biliary excretion of bile duct-cannulated rats. Ninety-eight drug compounds for which both human and rat absorption data...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0223-5234(03)00015-1
更新日期：2003-03-01 00:00:00
abstract：:Some novel pyrimidine-5-carbonitrile derivatives bearing various substituent have been synthesized. The structures of target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their cytotoxic potency against certain human tum...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.05.028
更新日期：2013-08-01 00:00:00
abstract：:Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2017.10.023
更新日期：2017-12-01 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：:Mono- and diacylated derivatives of galactopyranosyl amines were obtained from d-galactose, via aminated intermediates prepared by reaction of 6-deoxy-6-iodo-1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranose with 1,3-propanediamine, 1,2-ethanediamine or ethanolamine. Monoacylated derivatives displayed antitubercular...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2007.01.009
更新日期：2007-08-01 00:00:00
abstract：:A series of N6-aminopurine-9-β-D-ribonucleosides and ribose-modified 3'-C-methyl analogues substituted at N6-position with a small group like hydroxy, methoxy or amino group or at C2(N6) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N6-Hydrazino-9-β-D-ribofuranos...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.01.055
更新日期：2011-05-01 00:00:00
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
doi：10.1016/j.ejmech.2015.01.012
更新日期：2015-03-26 00:00:00
abstract：:Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become the world's leading killer disease due to a single infectious agent which survives in the host macrophage for the indefinite period. Hence, it is necessary to enhance the efficacy of the clinically existing antitubercular agents or to discover new...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.111713
更新日期：2019-12-01 00:00:00
abstract：:In recent years, drug discovery paradigm has been shifted from conventional single target inhibition toward multitarget design concept. In current research, we have reported synthesis, in-vitro, in-vivo and acute toxicity determination of N-substituted pyrrolidine-2,5-dione derivatives as multitarget anti-inflammatory...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.111863
更新日期：2020-01-15 00:00:00
abstract：:Vesicular Glutamate Transporters (VGLUTs) allow the loading of presynapic glutamate vesicles and thus play a critical role in glutamatergic synaptic transmission. VGLUTs have proved to be involved in several major neuropathologies and directly correlated to clinical dementia in Alzheimer and Parkinson's disease. Accor...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.03.056
更新日期：2014-05-06 00:00:00
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
doi：10.1016/s0223-5234(00)00156-2
更新日期：2000-06-01 00:00:00
abstract：:A series of novel 3-(1,2,4-triazol-1-yl)flavanones were synthesized based on the N-phenethylazole pharmacophore of azole antifungals. The results of antifungal assay revealed that 4'-fluoroflavanone derivative 4c exhibited the best profile of activity against Candida and Saccharomyces strains. Compound 4c was 4-16 tim...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.06.008
更新日期：2013-08-01 00:00:00
abstract：:Intrinsic resistance in Pseudomonas aeruginosa, defined by chromosomally encoded low outer membrane permeability and constitutively over-expressed efflux pumps, is a major reason why the pathogen is refractory to many antibiotics. Herein, we report that heterodimeric rifampicin-tobramycin conjugates break this intrins...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.04.034
更新日期：2019-07-15 00:00:00
abstract：:A series of new beta-carboline derivatives 3-14 bearing guanidinium group or amino group-terminated side chain targeting the TAR RNA were designed and synthesized. Molecular modeling studies indicated that the minimal interaction energy was obtained for compound 11, which contained the optimal linker of three methylen...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2005.01.012
更新日期：2005-09-01 00:00:00
abstract：:The synthesis of pyrrolo[2,3-e]indole derivatives with the structural characteristics of DNA bis- and mono-intercalators are described. A dihydro benzoindol analogue was also synthesised to elucidate the major structural requirements for cytotoxic activity. A biological evaluation of the test compounds was carried out...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0223-5234(01)01328-9
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abstract：:A new series of pyrimidine derivatives as human carbonic anhydrases (CA, EC 4.2.1.1) inhibitors is here designed by including a 5-fluorouracil (5-FU) moiety, broadly used anticancer medication, in nitrogenous base modulators of the tumor-associated CAs. Most sulfonamide derivatives efficiently inhibit the target CA IX...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112112
更新日期：2020-03-15 00:00:00
abstract：:A facile and efficient approach to the synthesis of prenylated flavonoids as potential chemopreventive agents has been described. This features the synthesis of prenyl halide, prenylation of p-hydroxybenzaldehyde, formation of prenylated polyhydroxychalcone and cyclization of prenylated polyhydroxychalcone to flavanon...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2005.09.008
更新日期：2006-02-01 00:00:00
abstract：:Antibiotic-resistant bacterial infections have seen a marked increase in recent years, while antibiotic discovery has waned. Resistance-modifying agents (RMA) offer an intriguing alternative strategy to fight against resistant bacteria. Here we report the discovery, antibiotic profiling, and structure-activity relatio...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.09.034
更新日期：2017-01-05 00:00:00
abstract：:Fungi, which can cause serious infections, results in more than 1.35 million deaths annually throughout the world. Azole antifungal drugs which could inhibit the enzyme lanosterol 14α-demethylase, occupy an important position in the treatment of fungal infections. Tetrazoles, practically non-metabolized bioisosteric a...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2019.03.023
更新日期：2019-05-15 00:00:00
abstract：:A series of novel hybrids β-carboline-4-thiazolidinones were synthesized and evaluated for their in vitro antitumor activity against human cancer cell lines and for antiviral activity towards Herpes simplex virus type-1 (HSV-1). From the N'-(2-ylidene-4-thiazolidinone)-β-carboline-3-carbohydrazide series (9-11), compo...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.10.018
更新日期：2016-11-29 00:00:00
abstract：:Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-β-lapachone-based 1,2,3-triazoles and ten α-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid compounds were evaluated for their activity against promastigot...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.02.038
更新日期：2013-05-01 00:00:00
abstract：:HIV-1 CA is involved in different stages of the viral replication cycle, performing essential roles in both early (uncoating, reverse transcription, nuclear import, integration) and late events (assembly). Recent efforts have demonstrated HIV-1 CA protein as a prospective therapeutic target for the development of new ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112085
更新日期：2020-03-15 00:00:00
abstract：:The self-assembly of the amyloid-β (Aβ) peptide of various amino acid lengths into senile plaques is one hallmark of Alzheimer's disease pathology. In the past decade, many small molecules, including NQTrp, have been identified to reduce aggregation and toxicity. However, due to the heterogeneity of the conformational...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.07.002
更新日期：2015-02-16 00:00:00
abstract：:The CXCR4/CXCL12 chemokine axis can chemotactically accumulate inflammatory cells to local tissues and regulate the release of inflammatory factors. Developing novel CXCR4 modulators may provide a desirable strategy to control the development of inflammation. A series of novel hybrids were designed by integrating the ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2018.02.085
更新日期：2018-04-25 00:00:00
abstract：:Derived from the structures of the alkaloids rutaecarpine and dehydroevodiamine (DHED), and the long-known acetylcholinesterase (AChE) inhibitor tacrine, respectively, novel compounds were synthesised, including: 13-methyl-5,8-dihydro-6H-isoquino[1,2-b]quinazolin-13-ium chloride (12), (8Z)-5,6-dihydro-8H-isoquino[1,2-...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2004.12.003
更新日期：2005-03-01 00:00:00
abstract：:Tyrosinase catalyzes two distinct sequential reactions in melanin biosynthesis: the hydroxylation of tyrosine to DOPA followed by the oxidation of DOPA to dopaquinone. The central roles of melanin in living species have motivated researchers to maintain constant efforts to discover new agents that modulate tyrosinase ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2015.10.033
更新日期：2015-12-01 00:00:00
