Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety.


:Fluorinated derivatives of 1,4-naphthoquinones are highly potent inhibitors of Cdc25A and Cdc25B phosphatases and growth of tumor cells. Eight new derivatives of polyfluoro-1,4-naphthoquinone were synthesized and their cytotoxicity in human myeloma, human mammary adenocarcinoma, mouse fibroblasts and primary mouse fibroblast cells as well as their mutagenic and antioxidant properties in a Salmonella tester strain were studied. The efficiency of suppressing the growth of two lines of tumor cells decreased in the order: 2-(2-hydroxy-ethylamino)-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (1), 2,3-dimethoxy-5,6,7,8-tetrafluoro-1,4-naphthoquinone (2), 2-[2-hydroxyethyl(methyl)amino]-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (3), 2-morpholino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (4), 2-[bis-(2-hydroxyethyl)amino]-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (5), 2-[(2-hydroxy)ethylsulfanyl)]-5,6,7,8-tetrafluoro-1,4-naphthoquinone (6), 2-methoxy-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (7), and 1,4-dioxo-3-(1-pyridinio)-1,4-dihydro-5,6,7,8-tetrafluoronaphthalene-2-olate (8). Taking into account these data together with the better cytotoxic effect against cancer cells as compared with normal mammalian cells, protecting of bacterial cells from spontaneous and H(2)O(2)-dependent mutagenesis, and lower general toxicity of the compounds towards different cells, one can propose that compounds 3-5 may be considered as useful potential inhibitors of growth of tumor cells.


Bioorg Med Chem


Zakharova OD,Ovchinnikova LP,Goryunov LI,Troshkova NM,Shteingarts VD,Nevinsky GA




Has Abstract


2011-01-01 00:00:00














  • Synthesis and photodynamic activity of zinc(II) phthalocyanine derivatives bearing methoxy and trifluoromethylbenzyloxy substituents in homogeneous and biological media.

    abstract::Two zinc(II) phthalocyanines bearing either four methoxy (ZnPc 3) or trifluoromethylbenzyloxy (ZnPc 4) substituents have been synthesized by a two-step procedure starting from 4-nitrophthalonitrile. Absorption and fluorescence spectroscopic studies were analyzed in different media. These compounds are essentially non-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yslas EI,Rivarola V,Durantini EN

    更新日期:2005-01-03 00:00:00

  • Synthesis and characterization of a small analogue of the anticancer natural product leinamycin.

    abstract::Leinamycin (1) is a Streptomyces-derived natural product that displays nanomolar IC(50) values against human cancer cell lines. In the work described here, we report the synthesis and characterization of a small leinamycin analogue 19 that closely resembles the 'upper-right quadrant' of the natural product, consisting...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Keerthi K,Rajapakse A,Sun D,Gates KS

    更新日期:2013-01-01 00:00:00

  • Design and synthesis of 3-fluoro-2-oxo-3-phenylpropionic acid derivatives as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase from pig liver.

    abstract::Several rationally designed analogs of 3-fluoro-2-oxo-3-phenylpropionic acid were chemically synthesized, and the reactions of the hydrate form of these compounds with 4-hydroxyphenylpyruvate dioxygenase from pig liver as inhibitors were examined. Compounds 14a and 14b were found to be potent competitive inhibitors of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ling TS,Shiu S,Yang DY

    更新日期:1999-07-01 00:00:00

  • New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.

    abstract::The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fortuna CG,Berardozzi R,Bonaccorso C,Caltabiano G,Di Bari L,Goracci L,Guarcello A,Pace A,Palumbo Piccionello A,Pescitelli G,Pierro P,Lonati E,Bulbarelli A,Cocuzza CE,Musumarra G,Musumeci R

    更新日期:2014-12-15 00:00:00

  • Conformational control of cyclosporin through substitution of the N-5 position. A new class of cyclosporin antagonists.

    abstract::Cyclosporin A (CsA) can be regiospecifically alkylated at the NH of Val-5 with reactive bromides in the presence of phosphazene-base P4-t-Bu to yield derivatives 2-5. These are devoid of immunosuppressive activity in vitro but they have binding affinity for cyclophilin A (CypA) similar to that of CsA and thus represen...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Papageorgiou C,Kallen J,France J,French R

    更新日期:1997-01-01 00:00:00

  • Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study.

    abstract::A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zarubaev VV,Morkovnik AS,Divaeva LN,Karpinskaya LA,Borodkin GS

    更新日期:2016-11-15 00:00:00

  • Parallel synthesis of a series of potentially brain penetrant aminoalkyl benzoimidazoles.

    abstract::Alpha7 agonists were identified via GOLD (CCDC) docking in the putative agonist binding site of an alpha7 homology model and a series of aminoalkyl benzoimidazoles was synthesised to obtain potentially brain penetrant drugs. The array was prepared starting from the reaction of ortho-fluoronitrobenzenes with a selectio...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Micco I,Nencini A,Quinn J,Bothmann H,Ghiron C,Padova A,Papini S

    更新日期:2008-03-01 00:00:00

  • Structure-activity studies of cyclic ketone inhibitors of the serine protease plasmin: design, synthesis, and biological activity.

    abstract::Three series of cyclic ketone inhibitors were synthesized and evaluated against the serine protease plasmin. Peptide inhibitors that incorporated 3-oxotetrahydrofuran and 3-oxotetrahydrothiophene 1,1-dioxide groups had the highest activities. Alkylamino substituents, which were designed to bind in the S1 subsite of pl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Xue F,Seto CT

    更新日期:2006-12-15 00:00:00

  • Synthesis and cytotoxic activities of usnic acid derivatives.

    abstract::Nine usnic acid-amine conjugates were evaluated on murine and human cancer cell lines. The polyamine derivatives showed significant cytotoxicity in L1210 cells. Their activities appeared to be independent of the polyamine transport system (PTS). Indeed, their activities were similar in chinese hamster ovary (CHO) and ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bazin MA,Le Lamer AC,Delcros JG,Rouaud I,Uriac P,Boustie J,Corbel JC,Tomasi S

    更新日期:2008-07-15 00:00:00

  • Metallocene-based antimalarials: an exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum.

    abstract::To establish the role of the ferrocenyl moiety in the antiplasmodial activity of ferroquine, compounds in which this moiety is replaced by the corresponding ruthenium-based moieties were synthesized and evaluated. In both the sensitive (D10) and resistant (K1) strains of Plasmodium falciparum, ruthenoquine analogues s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Blackie MA,Beagley P,Croft SL,Kendrick H,Moss JR,Chibale K

    更新日期:2007-10-15 00:00:00

  • Borrelidins F-I, cytotoxic and cell migration inhibiting agents from mangrove-derived Streptomyces rochei SCSIO ZJ89.

    abstract::Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sun J,Shao J,Sun C,Song Y,Li Q,Lu L,Hu Y,Gui C,Zhang H,Ju J

    更新日期:2018-05-01 00:00:00

  • Identification of novel thiazolo[5,4-d]pyrimidine derivatives as human A1 and A2A adenosine receptor antagonists/inverse agonists.

    abstract::In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A1, A2A, A2B ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Varano F,Catarzi D,Falsini M,Vincenzi F,Pasquini S,Varani K,Colotta V

    更新日期:2018-07-23 00:00:00

  • Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.

    abstract::Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Amano Y,Yamaguchi T,Tanabe E

    更新日期:2014-04-15 00:00:00

  • Scutione, a new bioactive norquinonemethide triterpene from Maytenus scutioides (Celastraceae).

    abstract::Scutione (1), a new norquinonemethide triterpene with a netzahualcoyene type skeleton, has been isolated from the root bark of Maytenus scutioides (Celastraceae) by bioactivity-directed fractionation. The structure of 1 has been elucidated by means of 1H and 13C NMR spectroscopic studies, including 1H-13C heteronuclea...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: González AG,Alvarenga NL,Ravelo AG,Bazzocchi IL,Ferro EA,Navarro AG,Moujir LM

    更新日期:1996-06-01 00:00:00

  • Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor treatment targeting lactate transport in cancer cells.

    abstract::Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential thera...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Draoui N,Schicke O,Fernandes A,Drozak X,Nahra F,Dumont A,Douxfils J,Hermans E,Dogné JM,Corbau R,Marchand A,Chaltin P,Sonveaux P,Feron O,Riant O

    更新日期:2013-11-15 00:00:00

  • Synthesis and cellular effects of cycloterpenals: cyclohexadienal-based activators of neurite outgrowth.

    abstract::An unusual class of diterpenoid natural products, 'cycloterpenals' (with a central cyclohexadienal core), that arise in nature by condensation of retinoids and other isoprenes, have been isolated from a variety of organisms including marine sponges as well as from the human eye. A milk whey protein has also demonstrat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bench BJ,Tichy SE,Perez LM,Benson J,Watanabe CM

    更新日期:2008-08-15 00:00:00

  • Electronic effects of para-substitution on acetophenones in the reaction of rat liver 3alpha-hydroxysteroid dehydrogenase.

    abstract::Stereoselective reductive metabolism of various p-substituted acetophenone derivatives was studied using isolated rat liver 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Kinetic experiments were performed and analyzed by measuring the products by HPLC using a chiral column. The results demonstrated that the presen...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Uwai K,Konno N,Yasuta Y,Takeshita M

    更新日期:2008-02-01 00:00:00

  • Protease inhibitors. Part 8: synthesis of potent Clostridium histolyticum collagenase inhibitors incorporating sulfonylated L-alanine hydroxamate moieties.

    abstract::A series of hydroxamates was prepared by reaction of alkyl/arylsulfonyl halides with N-2-chlorobenzyl-L-alanine, followed by conversion of the COOH moiety to the CONHOH group, with hydroxylamine in the presence of carbodiimides. Other structurally related compounds were obtained by reaction of N-2-chlorobenzyl-L-alani...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Scozzafava A,Supuran CT

    更新日期:2000-03-01 00:00:00

  • Anti-inflammatory properties of a heparin-like glycosaminoglycan with reduced anti-coagulant activity isolated from a marine shrimp.

    abstract::The anti-inflammatory properties of a heparin-like compound from the shrimp Litopenaeus vannamei are related. Besides reducing significantly (p<0.001) the influx of inflammatory cells to injury site in a model of acute inflammation, shrimp heparin-like compound was able to reduce the matrix metalloproteinase (MMPs) ac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brito AS,Arimatéia DS,Souza LR,Lima MA,Santos VO,Medeiros VP,Ferreira PA,Silva RA,Ferreira CV,Justo GZ,Leite EL,Andrade GP,Oliveira FW,Nader HB,Chavante SF

    更新日期:2008-11-01 00:00:00

  • One-pot enzymatic glycan remodeling of a therapeutic monoclonal antibody by endoglycosidase S (Endo-S) from Streptococcus pyogenes.

    abstract::A facile, one-pot enzymatic glycan remodeling of antibody rituximab to produce homogeneous high-mannose and hybrid type antibody glycoforms is described. This method was based on the unique substrate specificity of the endoglycosidase S (Endo-S) from Streptococcus pyogenes. While Endo-S efficiently hydrolyzes the bi-a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tong X,Li T,Orwenyo J,Toonstra C,Wang LX

    更新日期:2018-04-01 00:00:00

  • Benzimidazole inhibitors from the Niclosamide chemotype inhibit Wnt/β-catenin signaling with selectivity over effects on ATP homeostasis.

    abstract::The Wnt signaling pathway plays a key role in organ and tissue homeostasis, and when dysregulated, can become a major underlying mechanism of disease, particularly cancer. We reported previously that the anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mook RA Jr,Ren XR,Wang J,Piao H,Barak LS,Kim Lyerly H,Chen W

    更新日期:2017-03-15 00:00:00

  • Structure-activity relationships in platelet-activating factor. Part 14: synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 activity.

    abstract::As HIV-associated dementia prevalence has risen with the lifespan of HIV-infected individuals, there is an important need for antiretroviral and anti-inflammatory drugs targeting the central nervous system. Platelet-activating factor, a mediator of inflammation, is an HIV-induced neurotoxin secreted in the infected br...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sallem W,Serradji N,Dereuddre-Bosquet N,Dive G,Clayette P,Heymans F

    更新日期:2006-12-01 00:00:00

  • Expanding the repertoire of small molecule transcriptional activation domains.

    abstract::Molecules that can reconstitute the function of transcriptional activators hold enormous potential as therapeutic agents and as mechanistic probes. Previously we described an isoxazolidine bearing functional groups similar to natural transcriptional activators that up-regulates transcription 80-fold at 1 microM in cel...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Casey RJ,Desaulniers JP,Hojfeldt JW,Mapp AK

    更新日期:2009-02-01 00:00:00

  • Synthesis of novel Schiff base analogues of 4-amino-1,5-dimethyl-2-phenylpyrazol-3-one and their evaluation for antioxidant and anti-inflammatory activity.

    abstract::4-Aminoantipyrine (4-amino-1,5-dimethyl-2-phenylpyrazole-3-one) and its analogues have been found to be compounds of interest for their anti-inflammatory, analgesic, antiviral, antipyretic, antirheumatic and antimicrobial activities. In the present study, Schiff base analogues of 4-aminoantipyrine were synthesized by ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Alam MS,Choi JH,Lee DU

    更新日期:2012-07-01 00:00:00

  • Application of descriptors based on Lipinski's rules in the QSPR study of aqueous solubilities.

    abstract::We complement new physically interpretable descriptors inspired by the Lipinski's rules of drug bioavailability with others obtained from the Dragon 3.0 software, in order to find the best QSPR relationship for aqueous solubilities of 100 structurally heterogeneous organic, drug-like compounds. The simultaneous linear...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Duchowicz PR,Talevi A,Bellera C,Bruno-Blanch LE,Castro EA

    更新日期:2007-06-01 00:00:00

  • Photodynamic inactivation of Candida albicans using bridged polysilsesquioxane films doped with porphyrin.

    abstract::Novel photoactive bridged polysilsesquioxane films were prepared by doped with a porphyrin derivative. The films were formed by acid-catalyzed polycondensation reaction of a precursor of a bridged silsesquioxane, based on the reaction product of (glycidoxypropyl)trimethoxysilane with n-dodecylamine in the presence of ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Alvarez MG,Gómez ML,Mora SJ,Milanesio ME,Durantini EN

    更新日期:2012-07-01 00:00:00

  • Alkylation of a human telomere sequence by heterotrimeric chlorambucil PI polyamide conjugates.

    abstract::We designed and synthesized human telomere alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates (1-6). The C-type conjugates 1-3 possessed a chlorambucil moiety at the C terminus, whereas the N-type conjugates 4-6 had one of these moieties at the N terminus. The DNA alkylating activity of these conju...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kashiwazaki G,Bando T,Shinohara K,Minoshima M,Kumamoto H,Nishijima S,Sugiyama H

    更新日期:2010-04-15 00:00:00

  • Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosphonate linkages.

    abstract::Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG-motifs in a particular sequence context activate vertebrate immune cells. We examined the significance of negatively charged internucleoside linkages in the flanking sequences 5' and 3' to the CpG-motif on immunostimulatory activity. Cell pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu D,Kandimalla ER,Zhao Q,Cong Y,Agrawal S

    更新日期:2001-11-01 00:00:00

  • Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of dibenzofluorene derivatives.

    abstract::Highly regioselective electrophilic substitution of dibenzofluorene was achieved and the nitro derivative was transformed to a variety of new anticancer agents. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Becker FF,Mukhopadhyay C,Hackfeld L,Banik I,Banik BK

    更新日期:2000-12-01 00:00:00

  • Synthesis and cytotoxicity of methyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione derivatives.

    abstract::2- and 3-Methyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione and related derivatives were synthesized and evaluated in vitro by NCI against eight cancer types. Compounds 12-15 showed significant activity against melanoma, NCI-H23 non-small cell lung cancer, and MDA-MB-435 and MDA-N breast cancer cell lines; 2-h...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chao YH,Kuo SC,Ku K,Chiu IP,Wu CH,Mauger A,Wang HK,Lee KH

    更新日期:1999-06-01 00:00:00