当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and biological evaluation of novel thioquinazolinone-based 2-aminobenzamide derivatives as potent histone deacetylase (HDAC) inhibitors.

Design, synthesis and biological evaluation of novel thioquinazolinone-based 2-aminobenzamide derivatives as potent histone deacetylase (HDAC) inhibitors.

Abstract：

:A series of novel 2-aminobenzamide derivatives decorated with thioquinazolinone were designed and synthesized as histone deacetylase (HDAC) inhibitors. These derivatives were evaluated for their antiproliferative activities against several human cancer cell lines including A375, Hela, A549, HCT116 and SMMC7721. It's significantly indicated that some inhibitors exhibited potent antiproliferative activities towards all the studied cancer cell lines. Compounds 7a, 4i, 4o, and 4p exhibited higher antiproliferative activities towards three cancer cell lines: A375, A549 and SMMC7721 compared to CS055, MS275, and CI994. Compound 4p showed more than 4000-fold the isoform selectivity for HDAC1 and more than 250-fold selectivity for HDAC2 compared with HDAC6. The molecular docking analysis reasonably explained the HDAC inhibitory activity and isoform selectivity. In addition, compounds 7a, 4i, 4o, and 4p showed potent inhibitory activities in migration assay and colony formation analysis, and also promoted cell apoptosis. Moreover, compounds 7a, 4i, and 4o inhibited the growth of SMMC7721 cells at S phase of the cell cycle. The immunofluorometric analysis indicated that compounds 7a, 4i, 4o, and 4p could increase the acetylation status of H3K9. Furthermore, in vivo anticancer efficacy of compound 4p was assessed in the A549 xenograft models, and 4p demonstrated potent antitumor activity (TGI = 62.5%). This study provided an effective strategy for further development of tumor-targeting therapy.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Cheng C,Yun F,He J,Ullah S,Yuan Q

doi

10.1016/j.ejmech.2019.04.017

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

185-202

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(19)30323-X

journal_volume

173

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists.

    abstract：:GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112536

    authors： Sun N,Huang Y,Yu M,Zhao Y,Chen JA,Zhu C,Song M,Guo H,Xie Q,Wang Y

    更新日期：2020-09-15 00:00:00

  • Dependence of fungistatic activity of 2, 4-dihydroxythiobenzanilideson the structure and lipophilic nature of the compounds.

    abstract：:The quantitative dependencies of in vitro fungistatic action on the physico-chemical parameters connected with the structure of 2, 4-dihydroxythiobenzanilides were investigated. It was stated that the action of these compounds depends on lipophilicity determined by substitution of the N-aryl moiety and on electron pro...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(00)00136-7

    authors： Matysiak J,Niewiadomy A,Macik-Niewiadomy G,Kornillowicz T

    更新日期：2000-04-01 00:00:00

  • Synthesis and antimycobacterial activity of new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives.

    abstract：:As a continuation of our research and with the aim of obtaining new anti-tuberculosis agents which can improve the current chemotherapeutic anti-tuberculosis treatments, forty-three new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and evaluated for in vitro anti-tuberculosis activity against M...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.06.036

    authors： Moreno E,Ancizu S,Pérez-Silanes S,Torres E,Aldana I,Monge A

    更新日期：2010-10-01 00:00:00

  • Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer's disease.

    abstract：:Designing drugs with a specific multi-target profile is a promising approach against multifactorial illnesses as Alzheimer's disease. In this work, new indazole ethers that possess dual activity as both cannabinoid agonists CB2 and inhibitors of BuChE have been designed by computational methods. On the basis of this k...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.11.026

    authors： González-Naranjo P,Pérez-Macias N,Campillo NE,Pérez C,Arán VJ,Girón R,Sánchez-Robles E,Martín MI,Gómez-Cañas M,García-Arencibia M,Fernández-Ruiz J,Páez JA

    更新日期：2014-02-12 00:00:00

  • Synthesis, molecular docking and inhibition studies of novel 3-N-aryl substituted-2-heteroarylchromones targeting microtubule affinity regulating kinase 4 inhibitors.

    abstract：:A series of 3-N-aryl substituted-2-heteroarylchromones was efficiently synthesized via Pd-mediated oxidative coupling under the influence of hetero-atoms neighboring group participation. Synthesized molecules were evaluated against human microtubule affinity regulating kinase 4 (MARK4) enzyme inhibitors, a recently id...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.09.030

    authors： Parveen I,Khan P,Ali S,Hassan MI,Ahmed N

    更新日期：2018-11-05 00:00:00

  • Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains.

    abstract：:Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interesting derivatives of ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2006.11.014

    authors： Mordant C,Schmitt B,Pasquier E,Demestre C,Queguiner L,Masungi C,Peeters A,Smeulders L,Bettens E,Hertogs K,Heeres J,Lewi P,Guillemont J

    更新日期：2007-05-01 00:00:00

  • Design, synthesis and biological evaluation of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives as novel xanthine oxidase inhibitors.

    abstract：:A series of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives was designed, synthesized and evaluated for inhibitory potency in vitro against xanthine oxidase. The isonicotinamide series was considerably more effective than the nicotinamide series. SARs analysis revealed that the isonicotinoyl moiety ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.09.051

    authors： Zhang TJ,Li SY,Wang L,Sun Q,Wu QX,Zhang Y,Meng FH

    更新日期：2017-12-01 00:00:00

  • Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives.

    abstract：:With an aim to generate non-toxic, specific and highly potent multidrug resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted tariquidar derivatives were synthesized. The new compounds were evaluated for their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human gastric epit...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.06.049

    authors： Li XQ,Wang L,Lei Y,Hu T,Zhang FL,Cho CH,To KK

    更新日期：2015-08-28 00:00:00

  • Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines.

    abstract：:Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resis...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.02.047

    authors： Desplat V,Vincenzi M,Lucas R,Moreau S,Savrimoutou S,Pinaud N,Lesbordes J,Peyrilles E,Marchivie M,Routier S,Sonnet P,Rossi F,Ronga L,Guillon J

    更新日期：2016-05-04 00:00:00

  • Probes for narcotic receptor mediated phenomena 49. N-substituted rac-cis-4a-arylalkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.

    abstract：:Racemic N-substituted -1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols containing cis-4a-aralkyl groups were explored as probes for opioid receptors. Specifically cis-4a-phenylpropyl, -phenylbutyl, and-phenylpentyl groups coupled with widely varied substituents on the nitrogen atom were synthesized and their phar...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.01.025

    authors： Iyer MR,Rothman RB,Dersch CM,Jacobson AE,Rice KC

    更新日期：2015-03-06 00:00:00

  • 3,8-diazabicyclo--[3.2.1]-octane derivatives as analogues of ambasilide, a Class III antiarrhythmic agent.

    abstract：:Ambasilide, a representative of Class III antiarrhythmics, was reported to prolong the cardiac action potential duration in the dog, with little or no effect on Ca and Na currents. We synthesised a series of ambasilide analogues, having the 3,8-diazabicyclo-[3.2.1]-octane moiety instead of the 3,7-diazabicyclo-[3.3.1]...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(01)01246-6

    authors： Villa S,Barlocco D,Cignarella G,Papp GJ,Baláti B,Takács J,Varró A,Borosy A,Keserû K,Mátyus P

    更新日期：2001-06-01 00:00:00

  • Synthesis and primary cytotoxicity evaluation of new imidazo[2,1-b]thiazole derivatives.

    abstract：:A series of arylidenehydrazides (3a-3i) were synthesized from [6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid hydrazide. The structures of new compounds were determined by analytical and spectral (IR, (1)H NMR, (13)C NMR, EIMS) methods. The synthesized compounds (3a-3i) were evaluated in the National Cancer I...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2006.10.012

    authors： Gürsoy E,Güzeldemirci NU

    更新日期：2007-03-01 00:00:00

  • An exhaustive perspective on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent.

    abstract：:Diabetes mellitus is the global health issue and become an alarming threat in the modern era where human lifestyle gets compromised with modernization. According to the latest statistical report 2020, USA has 9.47% (31 million among 32.72 cr), China has 8.3% (116.4 million among 139.27 cr) and India has 5.6% (77 milli...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2020.112523

    authors： Bhattacharya S,Rathore A,Parwani D,Mallick C,Asati V,Agarwal S,Rajoriya V,Das R,Kashaw SK

    更新日期：2020-10-15 00:00:00

  • New chromene scaffolds for adenosine A(2A) receptors: synthesis, pharmacology and structure-activity relationships.

    abstract：:In silico screening of a collection of 1584 academic compounds identified a small molecule hit for the human adenosine A(2A) receptor (pK(i) = 6.2) containing a novel chromene scaffold (3a). To explore the structure-activity relationships of this new chemical series for adenosine receptors, a focused library of 43 2H-...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.05.009

    authors： Areias F,Costa M,Castro M,Brea J,Gregori-Puigjané E,Proença MF,Mestres J,Loza MI

    更新日期：2012-08-01 00:00:00

  • Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors.

    abstract：:To evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-D-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than the parent peptides, but dramatically weaker (4-5 ord...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.07.002

    authors： Campestre C,Tortorella P,Agamennone M,Preziuso S,Biasone A,Nuti E,Rossello A,Gallina C

    更新日期：2008-05-01 00:00:00

  • Progress of the synthesis of condensed pyrazole derivatives (from 2010 to mid-2013).

    abstract：:Condensed pyrazole derivatives are important heterocyclic compounds due to their excellent biological activities and have been widely applied in pharmaceutical and agromedical fields. In recent years, numerous condensed pyrazole derivatives have been synthesized and advanced to clinic studies with various biological a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2014.07.102

    authors： Li M,Zhao BX

    更新日期：2014-10-06 00:00:00

  • Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker.

    abstract：:Estradiol is the most potent estrogen in humans. It is known to be involved in the development and proliferation of estrogen dependent diseases such as breast cancer and endometriosis. The last step of its biosynthesis is catalyzed by 17β-hydroxysteroid dehydrogenase type 1 (17β- HSD1) which consequently is a promisin...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.05.074

    authors： Abdelsamie AS,Bey E,Hanke N,Empting M,Hartmann RW,Frotscher M

    更新日期：2014-07-23 00:00:00

  • α- and β-hydrazino acid-based pseudopeptides inhibit the chymotrypsin-like activity of the eukaryotic 20S proteasome.

    abstract：:We describe the synthesis of a library of new pseudopeptides and their inhibitory activity of the rabbit 20S proteasome chymotrypsin-like (ChT-L) activity. We replaced a natural α-amino acid by an α- or a β-hydrazino acid and obtained inhibitors of proteasome up to a submicromolar range (0.7 μM for molecule 24b). Stru...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.09.059

    authors： Bordessa A,Keita M,Maréchal X,Formicola L,Lagarde N,Rodrigo J,Bernadat G,Bauvais C,Soulier JL,Dufau L,Milcent T,Crousse B,Reboud-Ravaux M,Ongeri S

    更新日期：2013-01-01 00:00:00

  • Synthesis, characterization, evaluation and molecular dynamics studies of 5, 6-diphenyl-1,2,4-triazin-3(2H)-one derivatives bearing 5-substituted 1,3,4-oxadiazole as potential anti-inflammatory and analgesic agents.

    abstract：:A series of triazin-3(2H)-one derivatives bearing 1,3,4-oxadiazole (4a-4o) were synthesized, characterized and evaluated for anti-inflammatory and analgesic activities. Preliminary in vitro anti-inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in ac...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.06.020

    authors： Banerjee AG,Das N,Shengule SA,Srivastava RS,Shrivastava SK

    更新日期：2015-08-28 00:00:00

  • Design, synthesis and biological evaluation of novel α-acyloxy carboxamides via Passerini reaction as caspase 3/7 activators.

    abstract：:Evasion of apoptosis is a hallmark of cancer. Caspases; the key executors of apoptotic cascade are attractive targets for selective induction of apoptosis in cancer cells. Within this approach, various caspase activators were introduced as lead anticancer agents. In the current study, a new series of multifunctional P...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.02.051

    authors： Salah Ayoup M,Wahby Y,Abdel-Hamid H,Ramadan ES,Teleb M,Abu-Serie MM,Noby A

    更新日期：2019-04-15 00:00:00

  • A review of anti-infective and anti-inflammatory chalcones.

    abstract：:Chalcones, considered as the precursors of flavonoids and isoflavonoids, are abundant in edible plants, and have also been shown to display a diverse array of pharmacological activities. The purpose of this review is to provide an overview of the pharmacological activity of synthetic and naturally occurring chalcones....

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2006.09.019

    authors： Nowakowska Z

    更新日期：2007-02-01 00:00:00

  • Prodrugs of butyric acid. Novel derivatives possessing increased aqueous solubility and potential for treating cancer and blood diseases.

    abstract：:The synthesis and biological activities of acidic, basic and neutral types of butyric acid (BA) prodrugs possessing increased aqueous solubility are described. The compounds are butyroyloxyalkyl derivatives of carboxylic acids, which possess functionalities suitable for aqueous solubilization. The anticancer activity ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(00)01199-5

    authors： Nudelman A,Gnizi E,Katz Y,Azulai R,Cohen-Ohana M,Zhuk R,Sampson SR,Langzam L,Fibach E,Prus E,Pugach V,Rephaeli A

    更新日期：2001-01-01 00:00:00

  • Design and synthesis of aminothiazolyl norfloxacin analogues as potential antimicrobial agents and their biological evaluation.

    abstract：:A series of aminothiazolyl norfloxacin analogues as a new type of potential antimicrobial agents were synthesized and screened for their antimicrobial activities. Most of the prepared compounds exhibited excellent inhibitory efficiencies. Especially, norfloxacin analogue II-c displayed superior antimicrobial activitie...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2019.01.072

    authors： Wang LL,Battini N,Bheemanaboina RRY,Zhang SL,Zhou CH

    更新日期：2019-04-01 00:00:00

  • Design and regioselective synthesis of trifluoromethylquinolone derivatives as potent antimicrobial agents.

    abstract：:Three series of new trifluoromethyl substituted quinolone derivatives were synthesized (4a-f, 6a-f and 8a-f) from corresponding substituted anilines by multi-step reactions. The regioselective alkylation with different alkyl halides were carried out by approaching two different routes to get the final products in good...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.07.021

    authors： Garudachari B,Isloor AM,Satyanarayana MN,Fun HK,Pavithra N,Kulal A

    更新日期：2013-10-01 00:00:00

  • Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay.

    abstract：:In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.06.007

    authors： Rohe A,Göllner C,Wichapong K,Erdmann F,Al-Mazaideh GM,Sippl W,Schmidt M

    更新日期：2013-03-01 00:00:00

  • New styryl sulfones as anticancer agents.

    abstract：:New styryl sulfone compounds have been synthesized and evaluated for their anti-proliferative activity. Among the compounds synthesized, one compound (7k) has shown 51% tumor growth inhibition in mice implanted with HT-29 human carcinoma at 400 mg kg(-1) orally. ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(03)00144-2

    authors： Vedula MS,Pulipaka AB,Venna C,Chintakunta VK,Jinnapally S,Kattuboina VA,Vallakati RK,Basetti V,Akella V,Rajgopal S,Reka AK,Teepireddy SK,Mamnoor PK,Rajagopalan R,Bulusu G,Khandelwal A,Upreti VV,Mamidi SR

    更新日期：2003-09-01 00:00:00

  • Synthesis and anticancer activity of 6-heteroarylcoumarins.

    abstract：:A series of novel 7-hydroxy-8-methyl-coumarins with indole, pyrimidine, pyrazole, pyran, tetrazolo[1,5-a]pyrimidine, pyrimido[1,2-a]benzimidazol, 2-oxo-1,2-dihydropyridine and dihydropyrazolo[3,4-b]pyridine moieties at C6 position of heterocyclic core have been synthesized. Anticancer activity screening on NCI60 cell ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.10.021

    authors： Galayev O,Garazd Y,Garazd M,Lesyk R

    更新日期：2015-11-13 00:00:00

  • Synthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines.

    abstract：:We synthesized a series of novel amide derivatives of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid and assessed their antiproliferative activities against three human cancer cell lines (Huh7, human liver; MCF7, breast and HCT116, colon carcinoma cell lines) with the sulforhodamine B assay. Compound 4j with ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.09.056

    authors： Cankara Pirol Ş,Çalışkan B,Durmaz I,Atalay R,Banoglu E

    更新日期：2014-11-24 00:00:00

  • An insight into the biological activities of heterocyclic-fatty acid hybrid molecules.

    abstract：:Heterocyclic compounds are the interesting core structures for the development of new bioactive compounds. Fatty acids are derived from renewable raw materials and exhibit various biological activities. Several researchers are amalgamating these two bioactive components to yield bioactive hybrid molecules with some de...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2017.09.069

    authors： Venepally V,Reddy Jala RC

    更新日期：2017-12-01 00:00:00

  • Synthesis and antiproliferative activity of novel selenoester derivatives.

    abstract：:A series of 31 new selenoesters were synthesized and their cytotoxic activity was evaluated against a prostate cancer cell line (PC-3). The most active compounds were also tested against three tumoural cell lines (MCF-7, A-549 and HT-29) and one non-tumour prostate cell line (RWPE-1). Thirteen compounds showed signifi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.11.034

    authors： Domínguez-Álvarez E,Plano D,Font M,Calvo A,Prior C,Jacob C,Palop JA,Sanmartín C

    更新日期：2014-02-12 00:00:00