Abstract：
:A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring plays an essential role in compound activity. The most active agent (3f) inhibited at submicromolar concentrations the growth of tumor cell lines. It also inhibited tubulin polymerization with an activity quantitatively similar to that of CA-4, and treatment of HeLa cells resulted in their arrest at the G2-M phase of the cell cycle. Furthermore, 3f was effective against multidrug resistant cancer cells and inhibited the growth of the HT-29 xenograft in a nude mouse model. This indicated that 3f is a promising new antimitotic agent with encouraging preclinical potential.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Romagnoli R,Baraldi PG,Lopez Cara C,Kimatrai Salvador M,Bortolozzi R,Basso G,Viola G,Balzarini J,Brancale A,Fu XH,Li J,Zhang SZ,Hamel Edoi
10.1016/j.ejmech.2011.10.013subject
Has Abstractpub_date
2011-12-01 00:00:00pages
6015-24issue
12eissn
0223-5234issn
1768-3254pii
S0223-5234(11)00730-6journal_volume
46pub_type
杂志文章abstract：:Self-association, a process that competes with binding to DNA and formation of hetero-complexes, is studied in anticancer drugs 4'-epiadriamycin, adriamycin and daunomycin by proton nuclear magnetic resonance spectroscopy. The 2D nuclear Overhauser enhancement spectra yield several intra-molecular and inter-molecular ...
journal_title：European journal of medicinal chemistry
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abstract：:The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. T...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2014.10.076
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abstract：:A series of thirty two novel pyrrolo[2,3-b]pyridine analogues synthesized, characterized ((1)H NMR, (13)C NMR and MS) and cytotoxic evaluation of these molecules carried out over a panel of three human cancer cell lines including A549 (lung cancer), HeLa (cervical cancer) and MDA MB-231 (breast cancer), using sulforho...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.02.059
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abstract：:A set of novel selenium-containing heterocyclic analogues of combretastatin A-4 (CA-4) have been designed and synthesised using a rigid 1,2,5-selenadiazole as a linker to fix the cis-orientation of ring-A and ring-B. All of the target compounds were evaluated for their in vitro anti-proliferative activities. Among the...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.09.046
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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
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abstract：:For the optimization of the plakortin pharmacophore, we recently proposed a straightforward synthesis of 4-carbomethoxy-3-methoxy-1,2-dioxanes as potential antimalarial drug candidates. Herein we report the chemoselective reduction of the 4-carbomethoxy group which has allowed us to prepare in good yields twenty-four ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.10.050
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abstract：:Brain amyloid deposits have been identified as the main neuropathological hallmarks of Alzheimer's diseases (AD) and intensive efforts have been devoted to develop aggregation inhibitors preventing the formation of toxic oligomeric Aβ for therapeutic. In addition, evidence indicates that the formation and accumulation...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
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abstract：:Heme oxygenase (HO) is a cytoprotective enzyme that can be overexpressed in some pathological conditions, including certain cancers. In this work, novel imidazole derivatives were designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). In these compounds the imidazole ring, cruci...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2015.04.003
更新日期：2015-01-01 00:00:00
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.03.041
更新日期：2014-05-06 00:00:00
abstract：:Five dimeric oleanolic acids linked at C-28 by 1,6-hexanediamine, or built around the carbon chains of varying lengths between two carboxyl groups were synthesized, to investigate the effect of internal spacer length and species upon the stereochemical features and anti-tumor activity of the resultant bis-oleanolic ac...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.10.066
更新日期：2015-01-07 00:00:00
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.10.035
更新日期：2009-06-01 00:00:00
abstract：:Among the different classes of antibiotics, oxazolidinone derivatives represent important drugs, since their unique mechanism of action overcomes commonly diffused multidrug-resistant bacteria. Anyway, the structural similarity of these molecules to monoamino oxidase (MAO) inhibitors, like toloxatone and blefoxatone, ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.09.007
更新日期：2016-11-29 00:00:00
abstract：:The study described here concerns the synthesis of a series of thirty new symmetrically substituted imidothiocarbamate and imidoselenocarbamate derivatives and their evaluation for antitumoral activity in vitro against a panel of five human tumor cell lines: breast adenocarcinoma (MCF-7), colon carcinoma (HT-29), lymp...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2010.11.013
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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
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abstract：:Aurora Kinase B is a serine-threonine kinase known to be overexpressed in several cancers, with no inhibitors approved for clinical use. Herein, we present the discovery and optimization of a series of novel quinazoline-based Aurora Kinase B inhibitors. The lead inhibitor SP-96 shows sub-nanomolar potency in Aurora B ...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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abstract：:Targeted therapy has become an effective strategy of precision medicine for improving cancer treatment. Selectivity improvement is always popular in modern oncology because of decreased side effects in conventional cancer chemotherapy. The use of antibody-drug conjugates (ADC), a robust strategy for targeted therapy, ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2019-02-01 00:00:00
abstract：:A new series of substituted 8-fluro-4H-pyrimido[2,1-b] [1,3]benzothiazole-4-ones () substituted 7-methyl-4H-isoxazolo[2,3-a]pyrimidin-4-ones, and substituted 2-methyl-5,6,7,8-tetrahydro-9H-isoxazolo[2,3-a]pyridopyrimidin-9-ones, compounds I-VII, have been prepared via condensation of beta-keto esters with 2-aminopyrid...
journal_title：European journal of medicinal chemistry
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更新日期：2006-08-01 00:00:00
abstract：:A series of fifteen acetylcholinesterase inhibitors were designed and synthesised based upon the previously identified lead compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (5) which showed good inhibitory activity (IC50 0.03 ± 0.07 μM) against acetylcholinesterase. A series of c...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2019-10-01 00:00:00
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journal_title：European journal of medicinal chemistry
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更新日期：2011-02-01 00:00:00
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pub_type： 杂志文章,评审
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abstract：:Immunotherapy by cocaine-binding monoclonal antibodies (mAbs) has emerged as a promising strategy for the treatment of cocaine addiction. The human (gamma1 heavy chain)/murine (lambda light chain) chimeric mAb 2E2 has excellent affinity and specificity for cocaine and recent animal studies have demonstrated 2E2's abil...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2010-06-01 00:00:00
abstract：:In the search for novel hybrid molecules by fusing two biologically active scaffolds into one heteromeric chemotype, we found that hybrids of azithromycin and ciprofloxacin/gatifloxacin 26j and 26l can inhibit the supercoiling activity of E. coli gyrase by poisoning it in a way similar to fluoroquinolones. This may mo...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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更新日期：2013-08-01 00:00:00
abstract：:Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.05.046
更新日期：2016-10-04 00:00:00
abstract：:Human Golgi α-mannosidase II (hGM) is a pharmaceutical target for the design of inhibitors with anti-tumor activity. Nanomolar inhibitors of hGM exhibit unwanted co-inhibition of the human lysosomal α-mannosidase (hLM). Hence, improving specificity of the inhibitors directed toward hGM is desired in order to use them ...
journal_title：European journal of medicinal chemistry
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更新日期：2011-03-01 00:00:00
