当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and in vitro cell-free/cell-based biological evaluations of novel ERCC1-XPF inhibitors targeting DNA repair pathway.

Design, synthesis and in vitro cell-free/cell-based biological evaluations of novel ERCC1-XPF inhibitors targeting DNA repair pathway.

Abstract：

:The structure-specific ERCC1-XPF endonuclease is essential for repairing bulky DNA lesions and helix distortions induced by UV radiation, which forms cyclobutane pyrimidine dimers (CPDs), or chemicals that crosslink DNA strands such as cyclophosphamide and platinum-based chemotherapeutic agents. Inhibition of the ERCC1-XPF endonuclease activity has been shown to sensitize cancer cells to these chemotherapeutic agents. In this study, we have conducted a structure activity relationship analysis based around the previously identified hit compound, 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-methylpiperazin1-yl)methyl)phenol (F06), as a reference compound. Three different series of compounds have been rationally designed and successfully synthesized through various modifications on three different sites of F06 based on the corresponding suggestions of the previous pharmacophore model. The in vitro screening results revealed that 2-chloro-9-((3-((4-(2-(dimethylamino)ethyl)piperazin-1-yl)methyl)-4-hydroxyphenyl)amino)acridin-2-ol (B9) has a potent inhibitory effect on the ERCC1-XPF activity (IC50 = 0.49 μM), showing 3-fold improvement in inhibition activity compared to F06. In addition, B9 not only displayed better binding affinity to the ERCC1-XPF complex but also had the capacity to potentiate the cytotoxicity effect of UV radiation and inhibiting the nucleotide excision repair, by the inhibition of removal of CPDs, and cyclophosphamide toxicity to colorectal cancer cells.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Elmenoufy AH,Gentile F,Jay D,Karimi-Busheri F,Yang X,Soueidan OM,Mani RS,Ciniero G,Tuszynski JA,Weinfeld M,West FG

doi

10.1016/j.ejmech.2020.112658

subject

Has Abstract

pub_date

2020-10-15 00:00:00

pages

112658

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)30630-9

journal_volume

204

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on CoMFA.

    abstract：:Various substituted 3-aryl-1-isoquinolinamines were designed and synthesized based on the previously constructed CoMFA model. Most of the synthesized compounds showed excellent potency in eight different human tumor cell lines as expected. In order to find the exact cytotoxic mechanism of these 3-aryl-1-isoquinolinami...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.08.042

    authors： Yang SH,Van HT,Le TN,Khadka DB,Cho SH,Lee KT,Lee ES,Lee YB,Ahn CH,Cho WJ

    更新日期：2010-11-01 00:00:00

  • Synthesis and cancer cell growth inhibitory activity of icaritin derivatives.

    abstract：:A series of icaritin derivatives bearing carboxylic acid or carboxylic ester groups are synthesized, and their in vitro cytotoxic activity against three cancer cell lines, MCF-7, MDA-MB-435s, and A549, are evaluated by MTT assay. Several derivatives including 2h, 2j, 5b and 5d show higher cytotoxic activity than the p...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.06.006

    authors： Wang C,Wu P,Shi JF,Jiang ZH,Wei XY

    更新日期：2015-07-15 00:00:00

  • Synthesis and antiinflammatory activity of heterocyclic indole derivatives.

    abstract：:Chalcones of indole 1-5 and their corresponding products; pyrazolines 6-10 and azo compounds 11-15 were synthesised and evaluated for their antiinflammatory activity against carrageenan induced oedema in albino rats at a dose of 50 mg x kg(-1) oral. The structure of compounds was confirmed by IR, (1)H-NMR and mass spe...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2003.11.002

    authors： Rani P,Srivastava VK,Kumar A

    更新日期：2004-05-01 00:00:00

  • Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules and their antitubercular properties.

    abstract：:New series of quinoline-oxazolidinone hybrid molecules were synthesized based on the preliminary docking studies. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their antimycobacterial properties based on the promising preliminary antibact...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.07.049

    authors： Thomas KD,Adhikari AV,Chowdhury IH,Sandeep T,Mahmood R,Bhattacharya B,Sumesh E

    更新日期：2011-10-01 00:00:00

  • Synthesis, binding assays, cytotoxic activity and docking studies of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor.

    abstract：:Herein we report the design, synthesis, bioinformatic and biological studies of benzimidazole and benzothiophene derivatives as new cannabinoid receptor ligands. To test the hypothesis that the lack of a hydrogen bond interaction between benzimidazole and benzothiophene derivatives with Lys192 reduces their affinity f...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.08.005

    authors： Romero-Parra J,Mella-Raipán J,Palmieri V,Allarà M,Torres MJ,Pessoa-Mahana H,Iturriaga-Vásquez P,Escobar R,Faúndez M,Di Marzo V,Pessoa-Mahana CD

    更新日期：2016-11-29 00:00:00

  • Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents.

    abstract：:A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited pot...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.06.022

    authors： Luo W,Wang T,Hong C,Yang YC,Chen Y,Cen J,Xie SQ,Wang CJ

    更新日期：2016-10-21 00:00:00

  • Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents.

    abstract：:By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI₅₀...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.06.058

    authors： Chen TC,Yu DS,Huang KF,Fu YC,Lee CC,Chen CL,Huang FC,Hsieh HH,Lin JJ,Huang HS

    更新日期：2013-11-01 00:00:00

  • 2,2'-bipyridyl based copper complexes down regulate expression of pro-inflammatory cytokines and suppress MAPKs in mitogen induced Peripheral blood mononuclear cells.

    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

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.01.041

    authors： Rupesh KR,Priya AM,Sundarakrishnan B,Venkatesan R,Lakshmi BS,Jayachandran S

    更新日期：2010-06-01 00:00:00

  • Quantitative structure activity relationship studies of diaryl furanones as selective COX-2 inhibitors.

    abstract：:Selective COX-2 inhibitors have attracted much attention in recent times in the design of non-steroidal anti-inflammatory agents (NSAID), which are devoid of the common side effects of classical NSAIDs. QSAR studies have been performed on a series of diaryl furanones that acts as selective COX-2 inhibitor using Molecu...

    journal_title：European journal of medicinal chemistry

    pub_type： 更正并重新发布的文章,杂志文章

    doi：10.1016/j.ejmech.2004.06.005

    authors： Shahapurkar S,Pandya T,Kawathekar N,Chaturvedi SC

    更新日期：2004-10-01 00:00:00

  • 3-Pyrazolone analogues of the 3-isoxazolol metabotropic excitatory amino acid receptor agonist homo-AMPA. Synthesis and pharmacological testing.

    abstract：:We have previously shown that the higher homologue of (S)-glutamic acid [(S)-Glu], (S)-alpha-aminoadipic acid [(S)-alpha-AA] is selectively recognized by the mGlu(2) and mGlu(6) subtypes of the family of metabotropic glutamic acid (mGlu) receptors. Furthermore, a number of analogues of (S)-alpha-AA, in which the termi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(99)00122-1

    authors： Zimmermann D,Janin YL,Brehm L,Bräuner-Osborne H,Ebert B,Johansen TN,Madsen U,Krogsgaard-Larsen P

    更新日期：1999-11-01 00:00:00

  • Design and synthesis of chloroquine analogs with anti-breast cancer property.

    abstract：:A series of chloroquine (CQ) analogs were designed and synthesized in a repositioning approach to develop compounds with high anti-breast cancer property. The compounds were then examined for their antiproliferative effects on two human breast tumor cell lines and a matching non-cancer cell line. Although many of them...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.05.046

    authors： Solomon VR,Hu C,Lee H

    更新日期：2010-09-01 00:00:00

  • The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119.

    abstract：:A series of xanthine compounds derived from the previous hit 20i with modification on the terminal side chain was discovered through ring formation strategy. Systematic optimization of the compounds with rigid heterocycles in the hydrophobic side chain led to the new lead compound HBK001 (21h) with the improved DPP-IV...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.112017

    authors： Li G,Meng B,Yuan B,Huan Y,Zhou T,Jiang Q,Lei L,Sheng L,Wang W,Gong N,Lu Y,Ma C,Li Y,Shen Z,Huang H

    更新日期：2020-02-15 00:00:00

  • Structural insights into serotonin receptor ligands polypharmacology.

    abstract：:Identifying desired interactions with a target receptor is often the first step when designing new active compounds. However, attention should also be focused on contacts with other proteins that result in either selective or polypharmacological compounds. Here, the search for the structural determinants of selectivit...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.04.010

    authors： Podlewska S,Kafel R,Lacivita E,Satała G,Kooistra AJ,Vass M,de Graaf C,Leopoldo M,Bojarski AJ,Mordalski S

    更新日期：2018-05-10 00:00:00

  • Ni(II) curcumin complexes for cellular imaging and photo-triggered in vitro anticancer activity.

    abstract：:Nickel(II) complexes [Ni(cur)(L)2](OAc) (1-3) where L is N,N-donor heterocyclic bases namely 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2), dipyrido[3,2-a:2',3'-c]phenazine (dppz in 3) and Hcur is curcumin were prepared, fully characterized and light-induced in vitro anticancer activit...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112632

    authors： Banaspati A,Raza MK,Goswami TK

    更新日期：2020-10-15 00:00:00

  • Fructose-1,6-bisphosphatase inhibitors: A new valid approach for management of type 2 diabetes mellitus.

    abstract：:The rising incidence of diabetes and confines allied with clinical therapies emphasized the need to explore new molecular targets to develop novel, effective and safer antihyperglycemic agents. Excessive endogenous glucose production by gluconeogenesis is a primary determinant of hyperglycemia in patients with type 2 ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2017.09.029

    authors： Kaur R,Dahiya L,Kumar M

    更新日期：2017-12-01 00:00:00

  • Design, synthesis and biological evaluation of small-azo-dyes as potent Vesicular Glutamate Transporters inhibitors.

    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

    authors： Favre-Besse FC,Poirel O,Bersot T,Kim-Grellier E,Daumas S,El Mestikawy S,Acher FC,Pietrancosta N

    更新日期：2014-05-06 00:00:00

  • Highly potent non-steroidal FXR agonists protostane-type triterpenoids: Structure-activity relationship and mechanism.

    abstract：:Farnesoid X receptor (FXR) is a key regulator in charge of bile acid synthesis, transport, and metabolism. Activation of FXR represses bile acid synthesis and increases its excretion and transport, consequently protecting the liver functions. Thus, FXR is considered as a critical therapeutic target of cholestasis and ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.111652

    authors： Luan ZL,Huo XK,Dong PP,Tian XG,Sun CP,Lv X,Feng L,Ning J,Wang C,Zhang BJ,Ma XC

    更新日期：2019-11-15 00:00:00

  • Benzofuran derivatives as anticancer inhibitors of mTOR signaling.

    abstract：:A series of 32 derivatives and isosteres of the mTOR inhibitor 2 were synthesized and compared for their cytotoxicity in radioresistant SQ20B cancer cell line. Several of these compounds, in particular 30b, were significantly more cytotoxic than 2. Importantly, 30b was shown to block both mTORC1 and Akt signaling, sug...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.05.014

    authors： Salomé C,Ribeiro N,Chavagnan T,Thuaud F,Serova M,de Gramont A,Faivre S,Raymond E,Désaubry L

    更新日期：2014-06-23 00:00:00

  • Integrating docking scores, interaction profiles and molecular descriptors to improve the accuracy of molecular docking: toward the discovery of novel Akt1 inhibitors.

    abstract：:A set of forty-seven Akt1 inhibitors was used for the development of molecular docking based QSAR model by using nonlinear regression. The integration of docking scores, key interaction profiles and molecular descriptors remarkably improved the accuracy of the QSAR models, providing reasonable statistical parameters (...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.01.019

    authors： Zhan W,Li D,Che J,Zhang L,Yang B,Hu Y,Liu T,Dong X

    更新日期：2014-03-21 00:00:00

  • Biomimetic in vitro oxidation of lapachol: a model to predict and analyse the in vivo phase I metabolism of bioactive compounds.

    abstract：:The bioactive naphtoquinone lapachol was studied in vitro by a biomimetic model with Jacobsen catalyst (manganese(III) salen) and iodosylbenzene as oxidizing agent. Eleven oxidation derivatives were thus identified and two competitive oxidation pathways postulated. Similar to Mn(III) porphyrins, Jacobsen catalyst main...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.06.042

    authors： Niehues M,Barros VP,Emery Fda S,Dias-Baruffi M,Assis Md,Lopes NP

    更新日期：2012-08-01 00:00:00

  • Recent developments of quinolone-based derivatives and their activities against Escherichia coli.

    abstract：:Escherichia coli (E. coli) is the most common pathogen in both hospital and community settings, and is capable of causing infections that can lead to serious consequences. Quinolones, one of the most common antibiotics in clinical use, are effective weapons to treat E. coli infections. However, the resistance of E. co...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2018.08.095

    authors： Gao F,Wang P,Yang H,Miao Q,Ma L,Lu G

    更新日期：2018-09-05 00:00:00

  • Semi-synthesis and antitumor activity of 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives.

    abstract：:We recently discovered that 5, 8-O-dimethyl acylshikonin derivatives displayed the selectivity towards MCF-7 and no toxicity to normal cells. Herein, a series of the corresponding 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were synthesized starting from shikonin. In vitro evidence of the cytotoxicities indi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.05.006

    authors： Zhou W,Zhang X,Xiao L,Ding J,Liu QH,Li SS

    更新日期：2011-08-01 00:00:00

  • Stereospecific ligands and their complexes. Part VII. Synthesis, characterization and in vitro antitumoral activity of platinum(II) complexes with O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid.

    abstract：:Platinum(II) complexes (1-4) with bidentate N,N'-ligands, O,O'-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid were synthesized and characterized by IR, (1)H NMR and (13)C NMR spectroscopy and elemental analysis. DFT calculations were performe...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.07.034

    authors： Vujić JM,Kaluđerović GN,Milovanović M,Zmejkovski BB,Volarević V,Živić D,Đurđeviće P,Arsenijević N,Trifunović SR

    更新日期：2011-09-01 00:00:00

  • Structure activity relationship studies of natural product chemokine receptor CCR5 antagonist anibamine toward the development of novel anti prostate cancer agents.

    abstract：:Recent studies have indicated that the CCR5 chemokine receptor may be a potential target for treating prostate cancer. Thus, development of CCR5 antagonists may provide novel prostate cancer therapy. Anibamine, a novel pyridine quaternary alkaloid isolated from Aniba sp., was found to effectively compete with (125)I-g...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.07.049

    authors： Zhang F,Arnatt CK,Haney KM,Fang HC,Bajacan JE,Richardson AC,Ware JL,Zhang Y

    更新日期：2012-09-01 00:00:00

  • Dual-functional conjugates improving cancer immunochemotherapy by inhibiting tubulin polymerization and indoleamine-2,3-dioxygenase.

    abstract：:A series of novel conjugates comprising tublin and IDO inhibitors were designed, synthesized and evaluated for their antiproliferative activity. Among them, HI5, composed of combretastatin A-4 (CA-4) and (D)-1-methyltryptophan (D-MT) by a linker, exhibited the most potent antitumor activity, in particular with higher ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112041

    authors： Hua S,Chen F,Wang X,Gou S

    更新日期：2020-03-01 00:00:00

  • Hederagenin as a triterpene template for the development of new antitumor compounds.

    abstract：:In this study, a series of novel C-28 esters and amides derivatives of hederagenin (He) were designed and synthesized in attempt to develop potent antitumor agents. Their structures were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.10.006

    authors： Rodríguez-Hernández D,Demuner AJ,Barbosa LC,Csuk R,Heller L

    更新日期：2015-11-13 00:00:00

  • Synthesis of some new pyrimido[2',1':2,3]thiazolo[4,5-b]quinoxaline derivatives as anti-inflammatory and analgesic agents.

    abstract：:Treatment of 6-aminothiouracil (1) with 2,3-dichloroquinoxaline (2) in ethanol/TEA afforded 6-amino-2-(3-chloroquinoxalin-2-ylthio)pyrimidin-4(3H)-one (3), which was refluxed in DMF to give 2-aminopyrimido[2',1':2,3]thiazolo[4,5-b]quinoxaline-4-one (4). Compound 4 was utilized as a key intermediate for the synthesis o...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.01.042

    authors： Abu-Hashem AA,Gouda MA,Badria FA

    更新日期：2010-05-01 00:00:00

  • Structure-activity relationship studies of acridones as potential antipsoriatic agents. 2. Synthesis and antiproliferative activity of 10-substituted hydroxy-10H-acridin-9-ones against human keratinocyte growth.

    abstract：:A series of 10-substituted hydroxy-10H-acridin-9-ones were synthesized and studied as potential antipsoriatic agents. The antiproliferative activity of the novel derivatives, which can be considered as aza-analogues of the antipsoriatic drug anthralin, was determined using the human keratinocyte cell line HaCaT. Struc...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.08.059

    authors： Putic A,Stecher L,Prinz H,Müller K

    更新日期：2010-11-01 00:00:00

  • Design, synthesis and in vitro anti-influenza A virus evaluation of novel quinazoline derivatives containing S-acetamide and NH-acetamide moieties at C-4.

    abstract：:It is an urgent need to develop more effective anti-influenza agents due to the emergence of highly pathogenic and drug-resistant influenza viruses. Herein, a series of 2,4-disubstituted quinazoline derivatives were designed, synthesized and their antiviral activities against influenza A virus were evaluated. Nine com...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112706

    authors： Zhang G,Wang M,Zhao J,Wang Y,Zhu M,Wang J,Cen S,Wang Y

    更新日期：2020-11-15 00:00:00

  • Synthesis and biological screening of some novel amidocarbamate derivatives of ketoprofen.

    abstract：:A series of novel ketoprofen derivatives 4a-j bearing both amide and carbamate functionalities were prepared using benzotriazole. Selective reduction of ketoprofen produced hydroxy derivative 2, which reacts with one or 2 mol of 1-benzotriazole carboxylic acid chloride (1) gave benzotriazole derivatives 3a and 3b resp...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,收录出版

    doi：10.1016/j.ejmech.2010.04.008

    authors： Sahoo PK,Behera P

    更新日期：2010-07-01 00:00:00