Abstract：
:Developing new therapeutic strategies to overcome drug resistance of cancer cells is an ongoing endeavor. From among 2 million chemicals, we identified ethyl 4-oxo-2-phenyl-1,4-dihydroquinoline-6-carboxylate (AS1712) as a low-toxicity inhibitor of lung cancer cell proliferation and xenograft tumor growth. We show that AS1712 is active against broad cancer cell lines and is able to bind in the colchicine-binding pocket of β-tubulin, thereby inhibiting microtubule assembly and, consequently, inducing mitotic arrest and apoptosis. Our cell-based structure-activity relationship study identified a new lead compound, RJ-LC-15-8, which had a greater anti-proliferative potency for H1975 cells than did AS1712, while maintaining a similar mechanism of action. Notably, AS1712 and RJ-LC-15-8 overcame P-glycoprotein efflux pump and β-tubulin alterations that lead to acquired resistance against microtubule-targeting drugs of cancer cells. AS1712 and RJ-LC-15-8 may be lead compounds that overcome acquired resistance to microtubule-targeting agents of cancer cells.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Lin MS,Hong TM,Chou TH,Yang SC,Chung WC,Weng CW,Tsai ML,Cheng TR,Chen JJW,Lee TC,Wong CH,Chein RJ,Yang PCdoi
10.1016/j.ejmech.2019.111584subject
Has Abstractpub_date
2019-11-01 00:00:00pages
111584eissn
0223-5234issn
1768-3254pii
S0223-5234(19)30718-4journal_volume
181pub_type
杂志文章abstract：:Developing a model for predicting anticancer activity of any classes of organic compounds based on molecular structure is very important goal for medicinal chemist. Different molecular descriptors can be used to solve this problem. Stochastic molecular descriptors so-called the MARCH-INSIDE approach, shown to be very ...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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abstract：:cis-Jasmone, from jasmonoid group, is an important jasmine odor fragrance compound. The syntheses of new heterocyclic analogues of jasmone were described. Five analogues of this compound were prepared under microwave irradiation and the results of the microwave assisted syntheses were compared with classical, thermall...
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：:In the present paper, a fast and automated method for the synthesis of (13)N-labelled azo compounds is reported for the first time. The labelling strategy is based on trapping [(13)N]NO(2)(-) in an anion exchange resin. The reaction with primary aromatic amines in acidic media led to the formation of the corresponding...
journal_title：European journal of medicinal chemistry
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doi：10.1016/j.ejmech.2010.08.053
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abstract：:The 5,10-dihydro-2-thioxo-pyrimido[4,5-b]quinolines (2a-c) and its oxidized form 3 were prepared and used as key intermediates for the synthesis of thiazolo[3',2':1,2]pyrimido[4,5-b]-quinolines (5a-c), isoxazolo[5'',4'':4',5']thiazolo[3',2':1,2]pyrimido[4,5-b]quinolines (6a-c), 4-chloro-2-methylthio-pyrimido[4,5-b]qui...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.03.022
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abstract：:The present study aims at design and synthesis of newer gamma-aminobutyric acid (GABA) derivatives with the combination of thiosemicarbazone and GABA pharmacophores in order to develop newer anticonvulsants. The reported compounds were designed as bioisosteric analogues of GABA semicarbazones. The structures of the sy...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.01.036
更新日期：2008-12-01 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.2011.01.049
更新日期：2011-04-01 00:00:00
abstract：:Survival of the human malaria parasite Plasmodium falciparum is dependent on pantothenate (vitamin B5), a precursor of the fundamental enzyme cofactor coenzyme A. CJ-15,801, an enamide analogue of pantothenate isolated from the fungus Seimatosporium sp. CL28611, was previously shown to inhibit P. falciparum proliferat...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2017.08.050
更新日期：2018-01-01 00:00:00
abstract：:To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G120...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
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abstract：:Several new N-phenyl-1H-indazole-1-carboxamides 1c-h and 4l,m were prepared by reacting phenyl isocyanate derivatives 3a,b with 3-amino-1H-indazole derivatives 2c,e,g or 1H-indazole 2l respectively. Chemical transformations of compounds 1a,b and 1g,h gave 3-acetamido-N-phenyl-1H-indazole-1-carboxamide derivatives 5a,b...
journal_title：European journal of medicinal chemistry
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abstract：:Cardiovascular diseases are the leading cause of death in the world. Platelets have a major role in cardiovascular events as they bind to the damaged endothelium activating and forming thrombi. Although some hydroquinone scaffold-containing compounds have known antiplatelet activities, currently there is a lack of evi...
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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journal_title：European journal of medicinal chemistry
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abstract：:New benzofuranylthiazole derivatives containing the aryl-urea moiety were synthesized and evaluated in vitro as dual acetylcholinesterase (AChE)-butyrylcholinesterase (BuChE) inhibitors. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized com...
journal_title：European journal of medicinal chemistry
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abstract：PURPOSE:Among all genetic mutations of LRRK2, the G2019S mutation is the most commonly associated with the late-onset of Parkinson's disease (PD). Hence, one potential therapeutic approach is to block the hyperactivity of mutated LRRK2 induced by kinase inhibition. To date, only a few LRRK2 kinase inhibitors have been ...
journal_title：European journal of medicinal chemistry
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更新日期：2021-02-05 00:00:00
abstract：:Natural product-derived bengamides possess potent antiproliferative activity and target human methionine aminopeptidases for their cellular effects. Using bengamides as a template, several derivatives were designed and synthesized as inhibitors of methionine aminopeptidases of Mycobacterium tuberculosis, and initial a...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.11.017
更新日期：2012-01-01 00:00:00
abstract：:Two biologically active cyclic peptides, Yunnanin F 8 and Hymenistatin 16 were synthesized and the structures were established on the basis of analytical, IR, NMR and mass spectral data. The newly synthesized compounds were screened for their antimicrobial and pharmacological activities. These cyclic octapeptides have...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2004.11.013
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.12.012
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journal_title：European journal of medicinal chemistry
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abstract：:Four series of new 3-nitro naphthalimides derivatives, 4(4a‒4f), 5(5a‒5i), 6(6a‒6e) and 7 (7a‒7j), were designed and synthesized as antitumor agents. Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective in vitro antiproliferative activity on SMMC-7721, T24, SKOV-3...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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abstract：:2,2'-bipyridyl based copper complex I: [CuC24H22N6O10] at 10 nM and complex Ia: [Cu2C32H43N8O3](PF6)4 at 7 nM exhibited 50% inhibition of lymphocyte proliferation and less than 20% cytotoxicity in peripheral blood mononuclear cells (PBMCs). Further, pro-inflammatory cytokines such as TNF-alpha and IL-1beta and pro-inf...
journal_title：European journal of medicinal chemistry
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abstract：:A series of 2-(benzylthio)-5-aryloxadiazole derivatives have been designed and synthesized, and their biological activities are also evaluated for EGFR inhibitory activity. Fourteen compounds among the twenty compounds are reported for the first time. Their chemical structures are characterized by (1)H NMR, MS, and el...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.11.015
更新日期：2012-01-01 00:00:00
