Abstract:
:The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, herein we describe the synthesis of a new class of SAL analogues that combine key modifications at the C1 and C20 positions. The activity of the obtained SAL derivatives was evaluated using primary acute lymphoblastic leukemia, human breast adenocarcinoma and normal mammary epithelial cells. One single- [N,N-dipropyl amide of salinomycin (5 a)] and two novel double-modified analogues [N,N-dipropyl amide of C20-oxosalinomycin (5 b) and piperazine amide of C20-oxosalinomycin (13 b)] were found to be more potent toward the MDA-MB-231 cell line than SAL or its C20-oxo analogue 2. When select analogues were tested against the NCI-60 human tumor cell line panel, 4 a [N,N-diethyl amide of salinomycin] showed particular activity toward the ovarian cancer cell line SK-OV-3. Additionally, both SAL and 2 were found to be potent ex vivo against human ER/PR+ , Her2- invasive mammary carcinoma, with 2 showing minimal toxicity toward normal epithelial cells. The present findings highlight the therapeutic potential of SAL derivatives for select targeting of different cancer types.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Czerwonka D,Urbaniak A,Sobczak S,Piña-Oviedo S,Chambers TC,Antoszczak M,Huczyński Adoi
10.1002/cmdc.201900593subject
Has Abstractpub_date
2020-01-17 00:00:00pages
236-246issue
2eissn
1860-7179issn
1860-7187journal_volume
15pub_type
杂志文章相关文献
ChemMedChem文献大全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::Despite various inhibitors targeting the zinc center(s) of enzymes, drugs that target zinc fingers have not been examined in detail. We previously developed a dithiol compound named SN-1 that has an inhibitory effect on the function of zinc finger transcription factors, but its mechanism of action has not yet been elu...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700399
更新日期:2017-12-07 00:00:00
abstract::Opening up ion channels: We synthesised a series of anthraquinone analogues, called the GoSlo-SR family. Their effects on bladder smooth muscle BK channels were examined and, as shown, shifted voltage dependent activation >-100 mV (at 10 μM). They were more efficacious than NS11021 and could provide a new scaffold for...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200321
更新日期:2012-10-01 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::β-Alanyl-D-histidine (D-CAR, the enantiomer of the natural dipeptide carnosine) is a selective and potent sequestering agent of reactive carbonyl species (RCS) that is stable against carnosinase, but is poorly absorbed in the gastrointestinal tract. Herein we report a drug discovery approach aimed at increasing the or...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100042
更新日期:2011-07-04 00:00:00
abstract::Over the past few years, the number of people diagnosed with type 2 diabetes has increased owing to an unhealthy diet, a limited amount of exercise, and obesity. The search for novel and efficient antidiabetes agents has become an urgent task for scientists. Among the antidiabetes drugs, α-glucosidase inhibitor drugs ...
journal_title:ChemMedChem
pub_type: 杂志文章,评审
doi:10.1002/cmdc.201700216
更新日期:2017-06-07 00:00:00
abstract::A panel of new potential Ras ligands was generated by decorating a tricyclic levoglucosenone-derived scaffold with aromatic moieties. Some members of the panel show in vitro inhibitory activity toward the nucleotide exchange process on Ras and are toxic to some human cancer cell lines. ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800416
更新日期:2009-04-01 00:00:00
abstract::The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18 F-labeled derivative of the ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201800638
更新日期:2018-12-06 00:00:00
abstract::The in silico design, synthesis, and biological evaluation of ten potent type II dehydroquinase inhibitors are described. These compounds contain an anhydroquinate core, incorporated as a mimic of the enolate reaction intermediate. This substructure is attached by a variety of linking units to a terminal phenyl group ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700032
更新日期:2007-07-01 00:00:00
abstract::β-Sheet antimicrobial peptides (AMPs) are well recognized as promising candidates for the treatment of multidrug-resistant bacterial infections. To dissociate antimicrobial activity and hemolytic effect of β-sheet AMPs, we hypothesize that N-methylation of the intramolecular hydrogen bond(s)-forming amides could impro...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201300232
更新日期:2013-11-01 00:00:00
abstract::We recently reported the synthesis and biological evaluation of a novel series of 5-alkyl-2-(N,N-disubstituted)amino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones (F(2)-N,N-DABOs). These compounds are highly active against both wild-type HIV-1 and the K103N, Y181C, and Y188L mutant strains. Herein we pre...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800051
更新日期:2008-09-01 00:00:00
abstract::Members of the Eph receptor tyrosine kinase family play essential roles in the pathogenesis of cancer and are therefore promising candidates for molecular imaging by positron emission tomography (PET), for example. In this regard, radiochemical access to novel PET radiotracers derived from potent inhibitors that targe...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200264
更新日期:2012-11-01 00:00:00
abstract::Three photoswitchable tetrapeptides, based on a known synthetic antibacterial, were designed and synthesized to determine activity against Staphylococcus aureus. Each peptide contains an azobenzene photoswitch incorporated into either the N-terminal side chain (1), C-terminal side chain (2), or the C-terminus (3) to a...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000280
更新日期:2020-08-19 00:00:00
abstract::Half-sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7-trithiacyclononane [9]aneS(3) represent a promising class of apoptosis-inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000129
更新日期:2010-07-05 00:00:00
abstract::A historical overview of key events that led, 50 years ago, to the foundation of the European Federation for Medicinal Chemistry (EFMC), and the impact this had on promoting and structuring medicinal chemistry as a discipline in Europe. EFMC, together with the growing number of newly established national medicinal che...
journal_title:ChemMedChem
pub_type: 社论
doi:10.1002/cmdc.202000691
更新日期:2020-12-15 00:00:00
abstract::Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.202000858
更新日期:2020-12-06 00:00:00
abstract::A series of novel (R)/(S)-7-(3-alkoxyimino-2-aminomethyl-1-azetidinyl)fluoroquinolone derivatives were synthesized and evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that 12 of the target compounds generally show better activity (MIC: <0.008-0.5 μg mL(-1)) agains...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201200210
更新日期:2012-07-01 00:00:00
abstract::Cyclic RGD-containing functionalized azabicycloalkane peptides were synthesized with the aim of developing high-affinity selective integrin ligands as carriers for therapeutic and diagnostic purposes. Herein we describe the synthesis and in vitro screening of these RGD derivatives, as well as the determination of thei...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800422
更新日期:2009-04-01 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::The NLRP3 inflammasome is an important regulator of the sterile inflammatory response, and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL-1β)/IL-18, and pyroptotic cell death. Inappropriate activation ...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201700731
更新日期:2018-02-20 00:00:00
abstract::A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201100207
更新日期:2011-09-05 00:00:00
abstract::Having recently identified a so-far unexplored area adjacent to the known binding site of allosteric mitogen-activated protein kinase kinase (MEK) inhibitors, we now report an extension of these studies by combining our new side chains with different MEK inhibitor cores in a modular manner. Replacement of the amide he...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500442
更新日期:2015-12-01 00:00:00
abstract::A novel type of oligonucleotide has been developed, characterized by the attachment of a lysyl moiety to a 2'-O-aminohexyl linker. A protected lysine building block was tethered to 2'-O-aminohexyluridine, and the product was converted into the corresponding phosphoramidite. Up to six modified nucleosides were incorpor...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200700169
更新日期:2008-01-01 00:00:00
abstract::Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1'-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124 I isotope). The PET imaging ability and ex vivo biodistribution of [124 I]4 were compared with t...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201900352
更新日期:2019-08-20 00:00:00
abstract::Disulfide bridges that stabilize the native conformation of conotoxins pose a challenge in the synthesis of smaller conotoxin analogues. Herein we describe the synthesis of a minimized analogue of the analgesic mu-conotoxin KIIIA that blocks two sodium channel subtypes, the neuronal Na(V)1.2 and skeletal muscle Na(V)1...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200800292
更新日期:2009-03-01 00:00:00
abstract::The integrated stress response comprises multiple signaling pathways for detecting and responding to cellular stress that converge at a single event-the phosphorylation of Ser51 on the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α-P) results in attenuation of global p...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201500483
更新日期:2016-04-19 00:00:00
abstract::Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1beta and TNFalpha. Inhibition of p38 MAPK results in decreased expression of these cytokines. T...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.200900242
更新日期:2009-11-01 00:00:00
abstract::Identification of potent agonists of odorant receptors (ORs), a major class of G protein-coupled receptors, remains challenging due to complex receptor-ligand interactions. ORs are present in both olfactory and non-chemosensory tissues, indicating roles beyond odor detection that may include modulating physiological f...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201600612
更新日期:2017-04-06 00:00:00
abstract::A series of new 5-alkyl-2-phenylaminocarbonylmethylthiopyrimidin-4(3H)-ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti-HIV activity in MT-4 cells. Most of these new congeners exhibited moderate to good activities against the wild-...
journal_title:ChemMedChem
pub_type: 杂志文章
doi:10.1002/cmdc.201000555
更新日期:2011-05-02 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