Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: synthesis, crystal structure, antitumor activity and DNA interaction.

Abstract:

:Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu₂(PYP)₂Cl₄] (1), [Cu₄(PYP)₄(ClO₄)₂(H₂O)₂](ClO₄)₂·2H₂O (2), and [Cu₂(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tumor cell lines BEL-7404, SK-OV-3, A549, A375, MGC-803 and NCI-H460, with IC₅₀ values ranging from 0.31 to 30.76 μM. Complexes 1-3 exhibited lower cytotoxicity to HL-7702 than them to cancer cells. Complex 1 induced apoptotic death of BEL-7404, which involved mitochondria in the process. Caspase-3 activation assay indicated that 1 could be an efficient activator of caspase-3. DNA binding studies by UV-vis, DNA-melting, competitive binding, CD, viscosity measurement and agarose gel electrophoresis, revealed that intercalation might be the most likely binding mode of 1 with DNA.

journal_name

Eur J Med Chem

authors

Huang KB,Chen ZF,Liu YC,Wang M,Wei JH,Xie XL,Zhang JL,Hu K,Liang H

doi

10.1016/j.ejmech.2013.10.031

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

640-8

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(13)00672-7

journal_volume

70

pub_type

杂志文章
  • Synthesis, characterization and antihypertensive activity of pyridazinone derivatives.

    abstract::Some 6-(substituted-phenyl)-2-(substitutedmethyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by reacting 6-substituted-phenyl-4,5-dihydropyridazin-3(2H)-one with cyclic secondary amine under Mannich reaction conditions. The final compounds (15-70) were evaluated for antihypertensive activities by non-...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2010.02.003

    authors: Siddiqui AA,Mishra R,Shaharyar M

    更新日期:2010-06-01 00:00:00

  • Structural analysis of inhibition of Mycobacterium tuberculosis methionine aminopeptidase by bengamide derivatives.

    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

    authors: Lu JP,Yuan XH,Ye QZ

    更新日期:2012-01-01 00:00:00

  • Design and synthesis of novel SCM-198 analogs as cardioprotective agents: Structure-activity relationship studies and biological evaluations.

    abstract::SCM-198 (Leonurine) has attracted great attention due to its cardioprotective effects in myocardial infarction (MI). However, no systematic modifications and structure-activity relationship (SAR) studies could be traced so far. In this study, 35 analogs of SCM-198 were designed, synthesized and their cardioprotective ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2020.112469

    authors: Luo S,Xu S,Liu J,Ma F,Zhu YZ

    更新日期:2020-08-15 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

  • Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities.

    abstract::HIV-1 CA is involved in different stages of the viral replication cycle, performing essential roles in both early (uncoating, reverse transcription, nuclear import, integration) and late events (assembly). Recent efforts have demonstrated HIV-1 CA protein as a prospective therapeutic target for the development of new ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2020.112085

    authors: Sun L,Huang T,Dick A,Meuser ME,Zalloum WA,Chen CH,Ding X,Gao P,Cocklin S,Lee KH,Zhan P,Liu X

    更新日期:2020-03-15 00:00:00

  • Multifunctional 6-fluoro-3-[3-(pyrrolidin-1-yl)propyl]-1,2-benzoxazoles targeting behavioral and psychological symptoms of dementia (BPSD).

    abstract::Patients suffering from dementia experience cognitive deficits and 90% of them show non-cognitive behavioral and psychological symptoms of dementia (BPSD). The spectrum of BPSD includes agitation, depression, anxiety and psychosis. Antipsychotics, e.g. quetiapine, have been commonly used off-label to control the burde...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2020.112149

    authors: Bucki A,Marcinkowska M,Śniecikowska J,Zagórska A,Jamrozik M,Pawłowski M,Głuch-Lutwin M,Siwek A,Jakubczyk M,Pytka K,Jastrzębska-Więsek M,Partyka A,Wesołowska A,Mierzejewski P,Kołaczkowski M

    更新日期:2020-04-01 00:00:00

  • Combined inhibition of the EGFR/AKT pathways by a novel conjugate of quinazoline with isothiocyanate.

    abstract::Epidermal growth factor receptor inhibitors (EGFR-TKIs) represent a class of compounds widely used in anticancer therapy. An increasing number of studies reports on combination therapies in which the block of the EGFR-TK activity is associated with inhibition of its downstream pathways, as PI3K-Akt. Sulforaphane targe...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2016.04.002

    authors: Tarozzi A,Marchetti C,Nicolini B,D'Amico M,Ticchi N,Pruccoli L,Tumiatti V,Simoni E,Lodola A,Mor M,Milelli A,Minarini A

    更新日期:2016-07-19 00:00:00

  • Synthesis and biological evaluation of pyrrolo[2,3-b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA.

    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

    authors: Narva S,Chitti S,Bala BR,Alvala M,Jain N,Kondapalli VG

    更新日期:2016-05-23 00:00:00

  • Molecular insight into the inhibition mechanism of cyrtominetin to α-hemolysin by molecular dynamics simulation.

    abstract::The protein α-hemolysin (α-HL) is a self-assembling exotoxin that binds to the membrane of a susceptible host cell. In this paper, experimental studies show that cyrtominetin (CTM) can inhibit the hemolytic activity of α-HL. To understand how CTM can affect hemolytic activity, molecular dynamics simulations were carri...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.01.008

    authors: Niu X,Qiu J,Wang X,Gao X,Dong J,Wang J,Li H,Zhang Y,Dai X,Lu C,Deng X

    更新日期:2013-04-01 00:00:00

  • Synthesis and antibacterial activity of novel modified 5-O-mycaminose 14-membered ketolides.

    abstract::A practicable method of introducing a side chain to the C-4' position of 5-O-desosamine in the 14-membered ketolides was developed. And using this method, a series of novel modified 5-O-mycaminose ketolides were synthesized. These ketolides containing 5-O-4'-carbamate mycaminose were evaluated for their in vitro antib...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.08.023

    authors: Xu Y,Chen X,Zhu D,Liu Y,Zhao Z,Jin L,Liu C,Lei P

    更新日期:2013-11-01 00:00:00

  • Targeting Aryl hydrocarbon receptor for next-generation immunotherapies: Selective modulators (SAhRMs) versus rapidly metabolized ligands (RMAhRLs).

    abstract::Aryl Hydrocarbon Receptor (AhR) constitutes a major network hub of genomic and non-genomic signaling pathways, connecting host's immune cells to environmental factors. It shapes innate and adaptive immune processes to environmental stimuli with species-, cell- and tissue-type dependent specificity. Although an ever in...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.ejmech.2019.111842

    authors: Dolciami D,Ballarotto M,Gargaro M,López-Cara LC,Fallarino F,Macchiarulo A

    更新日期:2020-01-01 00:00:00

  • Additivity or cooperativity: which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?

    abstract::Predicting how binding affinity responds to ligand structural modifications in structure-activity relationship studies (SAR) is a major challenge in medicinal chemistry. This is particularly true when two or more of these modifications are carried out simultaneously. In this study, we present binding affinity data fro...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2014.11.056

    authors: Nasief NN,Hangauer D

    更新日期:2015-01-27 00:00:00

  • Synthesis, biological characterization and molecular modeling insights of spirochromanes as potent HDAC inhibitors.

    abstract::In the last decades, inhibitors of histone deacetylases (HDAC) have become an important class of anti-cancer agents. In a previous study we described the synthesis of spiro[chromane-2,4'-piperidine]hydroxamic acid derivatives able to inhibit histone deacetylase enzymes. Herein, we present our exploration for new deriv...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2015.11.010

    authors: Thaler F,Moretti L,Amici R,Abate A,Colombo A,Carenzi G,Fulco MC,Boggio R,Dondio G,Gagliardi S,Minucci S,Sartori L,Varasi M,Mercurio C

    更新日期:2016-01-27 00:00:00

  • Design, synthesis, and antibacterial activity of novel Schiff base derivatives of quinazolin-4(3H)-one.

    abstract::Novel imine derivatives of quinazolin-4(3H)-one were designed and synthesized by using aminoethyl moieties to increase the amine bridge of quinazolin-4(3H)-one amine and then introducing various aromatic aldehydes. The target compounds were characterized by proton nuclear magnetic resonance spectroscopy ((1)H NMR), ca...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2014.02.053

    authors: Wang X,Yin J,Shi L,Zhang G,Song B

    更新日期:2014-04-22 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

  • Indole based antimalarial compounds targeting the melatonin pathway: Their design, synthesis and biological evaluation.

    abstract::Malaria, one of the most severe global diseases, infects nearly 300 million people causing death of about a million population annually. Herein we have reported design, synthesis and biological evaluation of potent antimalarial compounds that target melatonin hormone as a potential pathway for the inhibition of the pa...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2019.02.019

    authors: Luthra T,Nayak AK,Bose S,Chakrabarti S,Gupta A,Sen S

    更新日期:2019-04-15 00:00:00

  • Synthesis and in vitro antiproliferative activity of new 1,3,4-oxadiazole derivatives possessing sulfonamide moiety.

    abstract::Synthesis of a new series of 1,3,4-oxadiazole derivatives possessing sulfonamide moiety is described. Their in vitro antiproliferative activities against NCI-58 human cancer cell lines of nine different cancer types were tested. Compound 1k with p-methoxybenzenesulfonamido moiety showed the highest mean %inhibition va...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2014.11.011

    authors: Gamal El-Din MM,El-Gamal MI,Abdel-Maksoud MS,Yoo KH,Oh CH

    更新日期:2015-01-27 00:00:00

  • Inhibition of pseudolysin and thermolysin by hydroxamate-based MMP inhibitors.

    abstract::In the present study, we have investigated the inhibition of thermolysin and pseudolysin by a series of compounds previously identified as matrix metalloproteinase (MMP) inhibitors using experimental binding studies and theoretical calculations. The experimental studies showed that some of the compounds were able to i...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2014.10.009

    authors: Adekoya OA,Sjøli S,Wuxiuer Y,Bilto I,Marques SM,Santos MA,Nuti E,Cercignani G,Rossello A,Winberg JO,Sylte I

    更新日期:2015-01-07 00:00:00

  • Structure activity relationships of quinoline-containing c-Met inhibitors.

    abstract::A series of quinoline-containing c-Met inhibitors were prepared and studied. Chemistry was developed to introduce a pyridyl moiety onto the 2-aryl ring present in a lead molecule which mitigated the potential for quinone formation relative to the original compound. The study also assessed the importance of an acylthio...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2007.08.011

    authors: Kung PP,Funk L,Meng J,Alton G,Padrique E,Mroczkowski B

    更新日期:2008-06-01 00:00:00

  • Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: synthesis, biological evaluation and molecular modeling studies.

    abstract::Continuous efforts in microwave-assisted synthesis and the structure-activity relationships' (SARs) studies of novel modified 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitriles, allowed identification of new amidine and imidate derivatives as potent and dual CDK1/GSK-3 inhibitors. Combination of lead optimization and mo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2007.09.020

    authors: Logé C,Testard A,Thiéry V,Lozach O,Blairvacq M,Robert JM,Meijer L,Besson T

    更新日期:2008-07-01 00:00:00

  • Synthesis and antiproliferative activity of novel polynuclear heterocyclic compounds derived from 2,3-diaminophenazine.

    abstract::2,3-Diaminophenazine 1 was used as a precursor for the preparation of some novel phenazine derivatives such as imidazo[4,5-b]phenazine-2-thione 2, its methylthio 3, ethyl 1-aryl-3H-[1,2,4]triazolo[2,3-a]imidazo[4,5-b]phenazines 8a-c, ethyl (2Z)-[3-aminophenazin-2-yl)amino](phenylhydrazono)ethanoate 9, pyrazino[2,3-b]p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.12.007

    authors: Mahran AM,Ragab SSh,Hashem AI,Ali MM,Nada AA

    更新日期:2015-01-27 00:00:00

  • 2-cinnamamido, 2-(3-phenylpropiolamido), and 2-(3-phenylpropanamido)benzamides: synthesis, antiproliferative activity, and mechanism of action.

    abstract::Several new benzamides 4a-q were synthesized by stirring in pyridine the acid chlorides 3a-q with the appropriate anthranilamide derivatives 2a-g. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.04.068

    authors: Raffa D,Maggio B,Raimondi MV,Cusimano MG,Amico G,Carollo A,Conaldi PG,Bai R,Hamel E,Daidone G

    更新日期:2013-07-01 00:00:00

  • Synthesis and biological screening for cytotoxic activity of N-substituted indolines and morpholines.

    abstract::Development of novel anticancer drugs is inevitable to improve treatment of cancers. In this study, novel derivatives of indoline and morpholine were synthesized and tested for their cytotoxic effects on osteosarcoma and Human Embryonic Kidney cells. To characterize cytotoxicity and the mechanism of cell death, we use...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2016.05.024

    authors: Doan P,Karjalainen A,Chandraseelan JG,Sandberg O,Yli-Harja O,Rosholm T,Franzen R,Candeias NR,Kandhavelu M

    更新日期:2016-09-14 00:00:00

  • Synthesis of C3-Neoglycosides of digoxigenin and their anticancer activities.

    abstract::Cardiac glycosides exhibit significant anticancer effects and the glycosyl substitution at C3 position of digoxigenin is pivotal for their biological activity. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and explore more potent anticancer agents, a series of C3-O-ne...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2017.12.086

    authors: Li XS,Ren YC,Bao YZ,Liu J,Zhang XK,Zhang YW,Sun XL,Yao XS,Tang JS

    更新日期:2018-02-10 00:00:00

  • Synthesis and biological evaluation of novel pyranochalcone derivatives as a new class of microtubule stabilizing agents.

    abstract::Twenty-five novel pyranochalcone derivatives were synthesized and evaluated for their in vitro and in vivo antiproliferative activities. Among them, compound 10i exhibited superior potent activity against 21 tumor cell lines including multidrug resistant phenotype with the IC50 values ranged from 0.09 to 1.30 μM. In a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.01.007

    authors: Cao D,Han X,Wang G,Yang Z,Peng F,Ma L,Zhang R,Ye H,Tang M,Wu W,Lei K,Wen J,Chen J,Qiu J,Liang X,Ran Y,Sang Y,Xiang M,Peng A,Chen L

    更新日期:2013-04-01 00:00:00

  • Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine.

    abstract::The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2009.01.010

    authors: Benchabane Y,Di Giorgio C,Boyer G,Sabatier AS,Allegro D,Peyrot V,De Méo M

    更新日期:2009-06-01 00:00:00

  • Design, synthesis, and in vitro cancer cell growth inhibition evaluation and antimalarial testing of trioxanes installed in cyclic 2-enoate substructures.

    abstract::A novel series of 1,2,4-trioxanes were synthesized from 2H-pyrans via photooxidation, and their antiproliferative and growth factor inhibitory activity has been investigated across a variety of human cancer cell lines. Compounds 5k, 5l, 5s, 7a and 7c exhibited the highest activity and selectivity against a human leuke...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2013.08.008

    authors: Hossain MI,Świtalska M,Peng W,Takashima M,Wang N,Kaiser M,Wietrzyk J,Dan S,Yamori T,Inokuchi T

    更新日期:2013-11-01 00:00:00

  • 5-Substituted [1]pyrindine derivatives with antiproliferative activity.

    abstract::We report herein the synthesis of 5-substituted [1]pyrindine derivatives and the evaluation of their antiproliferative properties on HeLa cells, a cervical carcinoma tumor cell line, and on the melanoma A2058 cell line. The most efficient compounds display cytotoxicity against tumor cells in the micromolar range but h...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2009.11.028

    authors: Kolb S,Goddard ML,Loukaci A,Mondésert O,Ducommun B,Braud E,Garbay C

    更新日期:2010-03-01 00:00:00

  • Design and synthesis of novel indole-chalcone fibrates as lipid lowering agents.

    abstract::A series of novel indole-chalcone fibrates were synthesized and their hypolipidemic activity was evaluated in triton WR-1339 induced hyperlipidemic rat model. Preliminary studies indicated that the hybrids 19, 24 and 29 exhibited potent in vitro antioxidant and significant in vivo antidyslipidemic effects. Our results...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2014.04.085

    authors: Sashidhara KV,Dodda RP,Sonkar R,Palnati GR,Bhatia G

    更新日期:2014-06-23 00:00:00

  • Improved synthesis and comparative analysis of the tool properties of new and existing D-ring modified (S)-blebbistatin analogs.

    abstract::(S)-Blebbistatin is a widely used research tool to study myosin II, an important regulator of many motility based diseases. Its potency is too low to be of clinical relevance, but identification of analogs with enhanced potency could deliver leads for targeted pharmacotherapeutics. This, however, requires a profound i...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.ejmech.2017.04.072

    authors: Verhasselt S,Roman BI,Bracke ME,Stevens CV

    更新日期:2017-08-18 00:00:00