Design, synthesis, and structure-activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents.

Abstract:

:A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to excellent activity against all the tested cell lines. Among them, compounds 15g (procaspase-3 EC50 = 1.42 μM) and 16b (procaspase-3 EC50 = 0.25 μM) exhibited excellent antitumor activity with IC50 values ranging from 0.14 μM to 0.98 μM against all cancer cell lines, which were 1.8-8.7 times more active than the first procaspase activating compound (PAC-1) (procaspase-3 EC50 = 4.08 μM). The structure-activity relationship (SAR) analyses indicated that the introduction of a lipophilic group (a benzyloxy or heteroaryloxy group) at the 4-position of the 2-hydroxy phenyl ring was beneficial to antitumor activity, and the presence of substituents containing nitrogen that are positively charged at physiological pH could also improve antitumor activity. It was also confirmed that the steric effect of the 4-position substituent of the benzyloxy group had a significant influence on cytotoxic activity.

journal_name

Eur J Med Chem

authors

Ma J,Chen D,Lu K,Wang L,Han X,Zhao Y,Gong P

doi

10.1016/j.ejmech.2014.08.058

subject

Has Abstract

pub_date

2014-10-30 00:00:00

pages

257-69

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(14)00793-4

journal_volume

86

pub_type

杂志文章
  • New 1,2,4-triazole-Chalcone hybrids induce Caspase-3 dependent apoptosis in A549 human lung adenocarcinoma cells.

    abstract::A series of novel 1, 2, 4-triazole/chalcone hybrids was prepared and identified with different spectroscopic techniques. The prepared compounds showed remarkable cytotoxic activity against different cancer cell lines. Compounds 24, 25, 27, 41 and 47 had shown the highest cytotoxicity among the tested compounds against...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2018.03.073

    authors: Ahmed FF,Abd El-Hafeez AA,Abbas SH,Abdelhamid D,Abdel-Aziz M

    更新日期:2018-05-10 00:00:00

  • Comparative study of microtubule inhibitors--estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation.

    abstract::The synthetic estramustine (EM) and natural podophyllotoxin (PODO) anti-mitotic agents that inhibit tubulin polymerization are known anticancer agents. As low bioavailability limits their anticancer properties, we investigated whether conjugation with PAMAM dendrimer (D) could enhance the activity of D-EM and D-PODO b...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.07.007

    authors: Sk UH,Dixit D,Sen E

    更新日期:2013-10-01 00:00:00

  • Discovery and structure-activity relationship of novel diphenylthiazole derivatives as BTK inhibitor with potent activity against B cell lymphoma cell lines.

    abstract::By the analysis of different binding modes with Bruton's tyrosine kinase (BTK), series of novel diphenylthiazole derivatives were rationally designed, synthesized and characterized. Biologically evaluation in biochemistry and cellular assay indicated that, compounds 5m, 5o, 6b, 6c, 6g, 6i, 7h, 7i, 7k, 7m, 7n, 7o and 7...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2019.06.035

    authors: Guo X,Yang D,Fan Z,Zhang N,Zhao B,Huang C,Wang F,Ma R,Meng M,Deng Y

    更新日期:2019-09-15 00:00:00

  • 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells.

    abstract::Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2016.05.004

    authors: Henry S,Kidner R,Reisenauer MR,Magedov IV,Kiss R,Mathieu V,Lefranc F,Dasari R,Evidente A,Yu X,Ma X,Pertsemlidis A,Cencic R,Pelletier J,Cavazos DA,Brenner AJ,Aksenov AV,Rogelj S,Kornienko A,Frolova LV

    更新日期:2016-09-14 00:00:00

  • Synthesis and evaluation of mutual prodrugs of ibuprofen with menthol, thymol and eugenol.

    abstract::The present works deals with simple and efficient method of improving therapeutic efficacy of racemic ibuprofen by retarding gastrointestinal side effects through masking of carboxylic group chemically. This is achieved by synthesis and evaluation of ester derivatives of ibuprofen as mutual prodrugs with naturally occ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2012.08.030

    authors: Redasani VK,Bari SB

    更新日期:2012-10-01 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, structure-activity relationship and trypanocidal activity of pyrazole-imidazoline and new pyrazole-tetrahydropyrimidine hybrids as promising chemotherapeutic agents for Chagas disease.

    abstract::Drug therapy for Chagas disease remains a major challenge as potential candidate drugs have failed clinical trials. Currently available drugs have limited efficacy and induce serious side effects. Thus, the discovery of new drugs is urgently needed in the fight against Chagas' disease. Here, we synthesized and evaluat...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2019.111610

    authors: Monteiro ME,Lechuga G,Lara LS,Souto BA,Viganó MG,Bourguignon SC,Calvet CM,Oliveira FOR Jr,Alves CR,Souza-Silva F,Santos MS,Pereira MCS

    更新日期:2019-11-15 00:00:00

  • Towards the development of 5-HT₇ ligands combining serotonin-like and arylpiperazine moieties.

    abstract::Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2014.04.034

    authors: Spadoni G,Bedini A,Bartolucci S,Pala D,Mor M,Riccioni T,Borsini F,Cabri W,Celona D,Marzi M,Tarzia G,Rivara S,Minetti P

    更新日期:2014-06-10 00:00:00

  • Synthesis and biological evaluation of novel 3,4-diaryl-1,2,5-selenadiazol analogues of combretastatin A-4.

    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

    authors: Guan Q,Yang F,Guo D,Xu J,Jiang M,Liu C,Bao K,Wu Y,Zhang W

    更新日期:2014-11-24 00:00:00

  • Prenylflavonoids and prenyl/alkyl-phloroacetophenones: synthesis and antitumour biological evaluation.

    abstract::Several prenylflavonoids have been synthesised and tested against human tumour cell lines. The prenyl unit has been geranyl or a labdane diterpene. These labdane-flavonoids have been synthesised for the first time. The antitumour activity increase with the prenylation at C-8 position. Twenty-three C and O-prenylated a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2010.06.025

    authors: Basabe P,de Román M,Marcos IS,Diez D,Blanco A,Bodero O,Mollinedo F,Sierra BG,Urones JG

    更新日期:2010-09-01 00:00:00

  • Evidence for a new binding mode to GSK-3: allosteric regulation by the marine compound palinurin.

    abstract::Glycogen synthase kinase 3β (GSK-3β) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer's disease, mood disorders, diabetes and cancer. Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitor...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2012.12.014

    authors: Bidon-Chanal A,Fuertes A,Alonso D,Pérez DI,Martínez A,Luque FJ,Medina M

    更新日期:2013-02-01 00:00:00

  • Synthesis and biological activities of dithiocarbamates containing 2(5H)-furanone-piperazine.

    abstract::A series of new dithiocarbamates containing a 2(5H)-furanone-piperazine group was synthesized. These compounds show good in vitro cytoxic activity. Among them, compound 6c exhibits the best inhibitory activity against HeLa cell lines with an IC50 of 0.06 ± 0.01 μM for 72 h, and it has good inhibitory activity against ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2018.05.056

    authors: Wei MX,Zhang J,Ma FL,Li M,Yu JY,Luo W,Li XQ

    更新日期:2018-07-15 00:00:00

  • Novel 2-aryl-4-(4'-hydroxyphenyl)-5H-indeno[1,2-b]pyridines as potent DNA non-intercalative topoisomerase catalytic inhibitors.

    abstract::On the basis of previous reports on the importance of thienyl, furyl or phenol group substitution on 5H-indeno[1,2-b]pyridine skeleton, a new series of rigid 2-aryl-4-(4'-hydroxyphenyl)-5H-indeno[1,2-b]pyridine derivatives were systematically designed and synthesized. Topoisomerase inhibitory activity and antiprolifer...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2016.09.019

    authors: Park S,Kadayat TM,Jun KY,Thapa Magar TB,Bist G,Shrestha A,Lee ES,Kwon Y

    更新日期:2017-01-05 00:00:00

  • Discovery of a benzenesulfonamide-based dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase that favorably modulates lipid mediator biosynthesis in inflammation.

    abstract::Leukotrienes (LTs) and prostaglandin (PG)E2, produced by 5-lipoxygenase (5-LO) and microsomal prostaglandin E2 synthase-1 (mPGES-1), respectively, are key players in inflammation, and pharmacological suppression of these lipid mediators (LM) represents a strategy to intervene with inflammatory disorders. Previous stud...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2018.07.031

    authors: Cheung SY,Werner M,Esposito L,Troisi F,Cantone V,Liening S,König S,Gerstmeier J,Koeberle A,Bilancia R,Rizza R,Rossi A,Roviezzo F,Temml V,Schuster D,Stuppner H,Schubert-Zsilavecz M,Werz O,Hanke T,Pace S

    更新日期:2018-08-05 00:00:00

  • Synthesis of stilbene derivatives with inhibition of SARS coronavirus replication.

    abstract::Stilbene derivatives have wide range of activities. In an effort to find other potential activities of this kind of compounds, 17 derivatives, including resveratrol, were synthesized. Twelve of them were evaluated for their antiviral potential against severe acute respiratory syndrome (SARS)-CoV-induced cytopathicity ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2006.03.024

    authors: Li YQ,Li ZL,Zhao WJ,Wen RX,Meng QW,Zeng Y

    更新日期:2006-09-01 00:00:00

  • Cyclocondensation reaction of heterocyclic carbonyl compounds. Part XIII: synthesis and cytotoxic activity of some 3,7-diaryl-5-(3,4,5-trimethoxyphenyl)pyrazolo[4,3-e][1,2,4]triazines.

    abstract::A series of the 3,7-diaryl-5-(3,4,5-trimethoxyphenyl)pyrazolo[4,3-e][1,2,4]triazines have been synthesized in five steps. The cytotoxic activity of all of the newly synthesized compounds has been tested in vitro against five cancer cell lines. Several compounds demonstrated significant broad cytotoxic activity in low ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2008.05.026

    authors: Gucký T,Frysová I,Slouka J,Hajdúch M,Dzubák P

    更新日期:2009-02-01 00:00:00

  • Novel cajaninstilbene acid derivatives as antibacterial agents.

    abstract::Discovery of novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Cajaninstilbene acid, which is isolated from pigeonpea leaves, has shown antibacterial activity. In this study, a series of cajaninstilbene acid derivatives were designed and synthesized. The a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2015.06.008

    authors: Geng ZZ,Zhang JJ,Lin J,Huang MY,An LK,Zhang HB,Sun PH,Ye WC,Chen WM

    更新日期:2015-07-15 00:00:00

  • 2-(2-Hydrazinyl)thiazole derivatives: design, synthesis and in vitro antimycobacterial studies.

    abstract::In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis (Mtb), a series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed by considering Lipinski rule. The designed compounds were synthesized, characterized and evaluated for their ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.08.054

    authors: Makam P,Kankanala R,Prakash A,Kannan T

    更新日期:2013-11-01 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

  • Studies on self-aggregation of anthracycline drugs by restrained molecular dynamics approach using nuclear magnetic resonance spectroscopy supported by absorption, fluorescence, diffusion ordered spectroscopy and mass spectrometry.

    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

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2008.09.037

    authors: Agrawal P,Barthwal SK,Barthwal R

    更新日期:2009-04-01 00:00:00

  • Design and studies of multiple mechanism of anti-Candida activity of a new potent Trp-rich peptide dendrimers.

    abstract:PURPOSE:Eight peptide dendrimers were designed as structural mimics of natural cationic amphiphilic peptides with antifungal activity and evaluated for their anti-Candida potential against the wild type strains and mutants. METHODS:Dendrimer 14 containing four Trp residues and dodecyl tail and a slightly smaller dendr...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2015.10.013

    authors: Zielińska P,Staniszewska M,Bondaryk M,Koronkiewicz M,Urbańczyk-Lipkowska Z

    更新日期:2015-11-13 00:00:00

  • Synthesis, transformation and biological evaluation of 2,3-secotriterpene acetylhydrazones and their derivatives.

    abstract::It has been previously shown that semi-synthetic A-secotriterpene acetylhydrazones of 1-cyano-28-methoxy-28-oxo-2,3-seco-2-norlup-20(29)-en-3-al and 1-cyano-2,3-seco-2-nor-19β,28-epoxy-18αH-olean-3-al (1, 2) inhibit the vesicular stomatitis virus (VSV) replication. To improve the antiviral activity against VSV, struct...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.07.016

    authors: Grishko VV,Tolmacheva IA,Galaiko NV,Pereslavceva AV,Anikina LV,Volkova LV,Bachmetyev BA,Slepukhin PA

    更新日期:2013-10-01 00:00:00

  • Chalcogen containing heterocyclic scaffolds: New hybrids with antitumoral activity.

    abstract::In this work, 27 novel hybrid derivatives containing diverse substituents with chalcogen atoms (selenium or sulfur) and several active heterocyclic scaffolds have been synthesized. Compounds were tested against two human cancer cells lines (MCF7 and PC-3) and a normal human mammary epithelial cell line (184B5) in orde...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2016.07.042

    authors: Alcolea V,Plano D,Encío I,Palop JA,Sharma AK,Sanmartín C

    更新日期:2016-11-10 00:00:00

  • Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction.

    abstract::We have synthesized bioactive 1,4-disubstituted 1,2,3-triazole analogues containing 2H-1,4-benzoxazin-3-(4H)-one derivatives via 1,3-dipolar cycloaddition in the presence of CuI. All the reactions proceeded smoothly and afforded its desired products in excellent yields. Among these analogues, 3y exhibited a better cyt...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2017.03.034

    authors: Su CL,Tseng CL,Ramesh C,Liu HS,Huang CF,Yao CF

    更新日期:2017-05-26 00:00:00

  • Novel 6β-acylaminomorphinans with analgesic activity.

    abstract::Aminomorphinans are a relatively young class of opioid drugs among which substances of high in vitro efficacy and favorable in vivo action are found. We report the synthesis and pharmacological evaluation of novel 6β-acylaminomorphinans. 6β-Morphinamine and 6β-codeinamine were stereoselectively synthesized by Mitsunob...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.09.031

    authors: Váradi A,Hosztafi S,Le Rouzic V,Tóth G,Urai Á,Noszál B,Pasternak GW,Grinnell SG,Majumdar S

    更新日期:2013-11-01 00:00:00

  • Novel 4-anilinoquinazoline derivatives featuring an 1-adamantyl moiety as potent EGFR inhibitors with enhanced activity against NSCLC cell lines.

    abstract::With the aim of overcoming gefitinib resistance, a series of novel quinazoline derivatives bearing an adamantyl group on the aniline ring were synthesized as potent epidermal growth factor receptor (EGFR) inhibitors. Most of these analogues are comparable to gefitinib in their ability to inhibit non-small cell lung ca...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2016.01.045

    authors: Yu H,Li Y,Ge Y,Song Z,Wang C,Huang S,Jin Y,Han X,Zhen Y,Liu K,Zhou Y,Ma X

    更新日期:2016-03-03 00:00:00

  • Rhodium(II) acetate-catalyzed stereoselective synthesis, SAR and anti-HIV activity of novel oxindoles bearing cyclopropane ring.

    abstract::Novel oxindole derivatives bearing substituted cyclopropane ring have been designed on the basis of docking studies with HIV-1 RT using the software DS 2.5 and synthesized as probable NNRTIs against HIV-1 using rhodium(II) acetate-catalyzed stereoselective cyclopropanation reaction. The cyclopropane isomer, having tra...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2011.01.037

    authors: Kumari G,Nutan,Modi M,Gupta SK,Singh RK

    更新日期:2011-04-01 00:00:00

  • Synthesis of some new 5-(2-substituted-1,3-thiazol-5-yl)-2-hydroxy benzamides and their 2-alkoxy derivatives as possible antifungal agents.

    abstract::The 2-hydroxy-5-(1,3-thiazol-5-yl) benzamide (4a), 5-(2-amino-1, 3-thiazol-5-yl)-2-hydroxy benzamide (4b), 2-hydroxy-5-(2-alkyl-1,3-Thiazol-5-yl) benzamide (4c and 4d), 5-(2-[(N-substituted aryl)amino]-1,3-thiazol-5-yl)2-hydroxy benzamides (6a-j) were prepared by reacting 5-(bromoacetyl) salicylamide (2) with thiourea...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2004.06.003

    authors: Narayana B,Vijaya Raj KK,Ashalatha BV,Kumari NS,Sarojini BK

    更新日期:2004-10-01 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

  • Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid.

    abstract::Structural modification of the frontline antitubercular isonicotinic acid hydrazide (INH) provides lipophilic adaptations (3-46) of the drug in which the hydrazine moiety of the parent compound has been chemically blocked from the deactivating process of N(2)-acetylation by N-arylaminoacetyl transferases. As a class, ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2009.05.009

    authors: Hearn MJ,Cynamon MH,Chen MF,Coppins R,Davis J,Joo-On Kang H,Noble A,Tu-Sekine B,Terrot MS,Trombino D,Thai M,Webster ER,Wilson R

    更新日期:2009-10-01 00:00:00