Identification of topoisomerases as molecular targets of cytosporolide C and its analog.


:Cytosporolide (Cytos) A-C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we synthesized Cytos C and measured cell growth-inhibiting activities of 7 compounds, including Cytos A and C, in several human cancer cell lines. Among these compounds, Cytos C and tetradeoxycytosporolide A (TD-Cytos A), a model compound for the synthesis of Cytos A, had anti-proliferative effects on cancer cells, and TD-Cytos A exhibited stronger activity than Cytos C. In vitro topoisomerase-mediated DNA relaxing experiments showed that TD-Cytos A inhibited the activities of topoisomerase I and II, whereas Cytos C targeted only topoisomerase I. These data suggest that the anti-proliferative activities of Cytos correlate with the inhibition of topoisomerases and implicated TD-Cytos A as a novel anti-cancer drug that suppresses the activities of topoisomerase I and II.


Bioorg Med Chem


Otake K,Yamada K,Miura K,Sasazawa Y,Miyazaki S,Niwa Y,Ogura A,Takao KI,Simizu S




Has Abstract


2019-08-01 00:00:00














  • 11H-Isoquino[4,3-c]cinnolin-12-ones; novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity.

    abstract::Recent studies have identified 2,3-dimethoxy-8,9-methylenedioxy-11-[(2-dimethylamino)ethyl]-11H-isoquino[4,3-c]cinnolin-12-one (1a) as a novel topoisomerase I-targeting agent with potent cytotoxic activity. The effect of varied substituents at the 11-position of 2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinn...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ruchelman AL,Singh SK,Ray A,Wu X,Yang JM,Zhou N,Liu A,Liu LF,LaVoie EJ

    更新日期:2004-02-15 00:00:00

  • Design and analysis of molecular motifs for specific recognition of RNA.

    abstract::Selective targeting of RNA has become a recent priority in drug design strategies due to the emergence of retroviruses, the need for new antibiotics to counter drug resistance, and our increased awareness of the essential role RNA and RNA structures play in the progression of disease. Most organic compounds known to s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li K,Fernandez-Saiz M,Rigl CT,Kumar A,Ragunathan KG,McConnaughie AW,Boykin DW,Schneider HJ,Wilson WD

    更新日期:1997-06-01 00:00:00

  • Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors.

    abstract::Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Osada S,Sano S,Ueyama M,Chuman Y,Kodama H,Sakaguchi K

    更新日期:2010-01-15 00:00:00

  • Synthesis, incorporation efficiency, and stability of disulfide bridged functional groups at RNA 5'-ends.

    abstract::Modified guanosine monophosphates have been employed to introduce various functional groups onto RNA 5'-ends. Applications of modified RNA 5'-ends include the generation of functionalized RNA libraries for in vitro selection of catalytic RNAs, the attachment of photoaffinity-tags for mapping RNA-protein interactions o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sengle G,Jenne A,Arora PS,Seelig B,Nowick JS,Jäschke A,Famulok M

    更新日期:2000-06-01 00:00:00

  • A laccase-catalysed one-pot synthesis of aminonaphthoquinones and their anticancer activity.

    abstract::Nuclear monoamination of a 1,4-naphthohydroquinone with primary aromatic amines was catalysed by the commercial laccase, Novozym 51003, from Novozymes to afford aminonaphthoquinones. The synthesis was accomplished by reacting a mixture of the primary amine and 1,4-naphthohydroquinone in succinate-lactate buffer and a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wellington KW,Kolesnikova NI

    更新日期:2012-07-15 00:00:00

  • Synthesis and antimicrobial activity of dermaseptin S1 analogues.

    abstract::Dermaseptins are peptides found in the skin secretions of Phyllomedusinae frogs. These peptides exert lytic action on some microorganisms without substantial haemolysis. In an attempt to understand the antimicrobial activity of these peptides we designed several dermaseptin S1 (ALWKTMLKKLGTMALHAGKAALGAAADTISQGTQ) (DS1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Savoia D,Guerrini R,Marzola E,Salvadori S

    更新日期:2008-09-01 00:00:00

  • Identification of a novel hormone sensitive lipase inhibitor with a reduced potential of reactive metabolites formation.

    abstract::Hormone sensitive lipase (HSL) has emerged as an attractive target for the treatment of dyslipidemia. We previously reported compound 1 as a potent and orally active HSL inhibitor. Although an attractive profile was demonstrated, subsequent studies revealed that compound 1 has a bioactivation liability. The oxygen-car...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ogiyama T,Yamaguchi M,Kurikawa N,Honzumi S,Yamamoto Y,Sugiyama D,Takakusa H,Inoue SI

    更新日期:2017-04-01 00:00:00

  • Synthesis of chlorogenic acid derivatives with promising antifungal activity.

    abstract::Derivatives of chlorogenic acid or its analogues were synthesized by coupling protected chlorogenic acid or its analogues with p-octyloxyaniline and selected amino acids. Most of the compounds exhibited significant potency against Cryptococcus neoformans and Candida species with low toxicity to brine shrimps. The 4,5-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ma CM,Kully M,Khan JK,Hattori M,Daneshtalab M

    更新日期:2007-11-01 00:00:00

  • Chemoenzymatic synthesis of CMP-sialic acid derivatives by a one-pot two-enzyme system: comparison of substrate flexibility of three microbial CMP-sialic acid synthetases.

    abstract::Three C terminal His6-tagged recombinant microbial CMP-sialic acid synthetases [EC] cloned from Neisseria meningitidis group B, Streptococcus agalactiae serotype V, and Escherichia coli K1, respectively, were evaluated for their ability in the synthesis of CMP-sialic acid derivatives in a one-pot two-enzyme s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu H,Yu H,Karpel R,Chen X

    更新日期:2004-12-15 00:00:00

  • Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors.

    abstract::Therapeutic development of a targeted agent involves a series of decisions over additional activities that may be ignored, eliminated or pursued. This paper details the concurrent application of two methods that provide a spectrum of information about the biological activity of a compound: biochemical profiling on a l...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ross-Macdonald P,de Silva H,Patel V,Truong A,He A,Neuhaus I,Tilford C,Ji R,Siemers N,Greer A,Carboni J,Gottardis M,Menard K,Lee F,Dodier M,Frennesson D,Sampognaro A,Saulnier M,Trainor G,Vyas D,Zimmermann K,Wittm

    更新日期:2012-03-15 00:00:00

  • Apoptosis-inducing effect of epolactaene derivatives on BALL-1 cells.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kuramochi K,Matsui R,Matsubara Y,Nakai J,Sunoki T,Arai S,Nagata S,Nagahara Y,Mizushina Y,Ikekita M,Kobayashi S

    更新日期:2006-04-01 00:00:00

  • QSAR study of antiplatelet agents.

    abstract::A QSAR methodology that involves multilinear (Hansch-type) and nonlinear (ANN backpropagation) approaches was developed to correlate the antiplatelet activity of 60 benzoxazinone derivatives against factor Xa. The statistical characteristics provided by multilinear model (R2 = 0.821) indicated satisfactory stability a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Katritzky AR,Pacureanu LM,Slavov S,Dobchev DA,Karelson M

    更新日期:2006-11-15 00:00:00

  • Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C.

    abstract::Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical balance between ceramide and sphingosine-1-phosphate. Much effort has been dedicated to develop inhibitors against these enzymes. Naturally occurring pachastrissamine (jaspine B) and all its stereoisomers were prepared and evaluated for their...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yoshimitsu Y,Oishi S,Miyagaki J,Inuki S,Ohno H,Fujii N

    更新日期:2011-09-15 00:00:00

  • Structural studies of β-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Schmidt J,Patora-Komisarska K,Moehle K,Obrecht D,Robinson JA

    更新日期:2013-09-15 00:00:00

  • Modulating amyloid-β aggregation: The effects of peptoid side chain placement and chirality.

    abstract::Alzheimer's disease (AD) is characterized by the buildup of insoluble aggregated amyloid-β protein (Aβ) into plaques that accumulate between the neural cells in the brain. AD is the sixth leading cause of death in the United States and is the only cause of death among the top ten that cannot currently be treated or cu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Turner JP,Chastain SE,Park D,Moss MA,Servoss SL

    更新日期:2017-01-01 00:00:00

  • New diterpenoids and the bioactivity of Erythrophleum fordii.

    abstract::A phytochemical investigation of the leaves of Erythrophleum fordii Oliv. has led to the isolation of three new cassaine-type diterpenoids, erythrofordin A (1), erythrofordin B (2) and erythrofordin C (3), as well as a norcassaine diterpenoid with a novel skeleton, norerythrofordin A (4), and 27 known compounds (5-31)...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tsao CC,Shen YC,Su CR,Li CY,Liou MJ,Dung NX,Wu TS

    更新日期:2008-11-15 00:00:00

  • Synthesis and evaluation of novel amide amino-β-lactam derivatives as cholesterol absorption inhibitors.

    abstract::The β-lactam cholesterol absorption inhibitor ezetimibe is so far the only representative of this class of compounds on the market today. The goal of this work was to synthesize new amide ezetimibe analogs from trans-3-amino-(3R,4R)-β-lactam and to test their cytotoxicity and activity as cholesterol absorption inhibit...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Dražić T,Sachdev V,Leopold C,Patankar JV,Malnar M,Hećimović S,Levak-Frank S,Habuš I,Kratky D

    更新日期:2015-05-15 00:00:00

  • In-situ side-chain peptide cyclization as a breaker strategy against the amyloid aggregating peptide.

    abstract::Accumulation and deposition of misfolded amyloid β (Aβ) peptide outside the nerve cells are one of the major causes of Alzheimer's disease (AD). To date, one of the promising therapeutic strategies for AD is to block the early steps associated with the aggregation of Aβ peptide. We have developed synthetic breaker pep...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ghosh N,Kundu LM

    更新日期:2021-01-16 00:00:00

  • Chemical studies on antioxidant mechanism of tea catechins: analysis of radical reaction products of catechin and epicatechin with 2,2-diphenyl-1-picrylhydrazyl.

    abstract::Tea catechins, an important class of polyphenols, have been shown to have wide spectrum of antitumor activity believed to be due mainly to their antioxidative effect. In this study, the radical scavenging behavior of catechins on 2,2-diphenyl-1-picrylhydrazyl (DPPH) was studied. Two reaction products of (+)-catechin, ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sang S,Cheng X,Stark RE,Rosen RT,Yang CS,Ho CT

    更新日期:2002-07-01 00:00:00

  • Cembrane diterpenoids from the soft coral Sarcophyton trocheliophorum Marenzeller as a new class of PTP1B inhibitors.

    abstract::A detailed investigation of the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller yielded, along with six known terpenes (6-11), the new sarcophytonolides N-R (1-5), whose structures have been elucidated by detailed spectroscopic analysis. Sarcophytonolides N-R are mono- or bicyclic cembranoids charac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Liang LF,Gao LX,Li J,Taglialatela-Scafati O,Guo YW

    更新日期:2013-09-01 00:00:00

  • The square conformation of phenylglycine-incorporated ascidiacyclamide is stabilized by CH/π interactions between amino acid side chains.

    abstract::We designed a phenylglycine (Phg)-incorporated ascidiacyclamide (ASC) analogue, cyclo(-Phg-oxazoline-d-Val-thiazole-Ile-oxazoline-d-Val-thiazole- ([Phg]ASC), with the aim of stabilizing the square conformation of ASC through interactions between amino acid side chains. X-ray diffraction analysis showed that [Phg]ASC h...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Asano A,Yamada T,Doi M

    更新日期:2011-06-01 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

  • Synthesis and in vitro cytotoxicity of haloderivatives of noscapine.

    abstract::Three haloderivatives of noscapine 2-4 were synthesized chemoselectively and their in vitro cytotoxicity was assessed by MTT assay on U-87 human glioblastoma cell lines. At 50 microM concentration after 72 h, 9-chloronoscapine 2, 9-bromonoscapine 3 (EM011), and 9-iodonoscapine 4 killed 87.8%, 51.2%, and 56.8% cells, r...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Verma AK,Bansal S,Singh J,Tiwari RK,Kasi Sankar V,Tandon V,Chandra R

    更新日期:2006-10-01 00:00:00

  • Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice.

    abstract::Sustained activation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway contributed to the progression of cancer and liver diseases. STAT3 signaling inhibitor has been extensively investigated for pharmacological use. We synthesized a series of andrographolide derivatives, and ch...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chen SR,Li F,Ding MY,Wang D,Zhao Q,Wang Y,Zhou GC,Wang Y

    更新日期:2018-10-01 00:00:00

  • New substrates and inhibitors of gamma-aminobutyric acid aminotransferase containing bioisosteres of the carboxylic acid group: design, synthesis, and biological activity.

    abstract::A series of potential substrates of gamma-aminobutyric acid aminotransferase (GABA-AT) with lipophilic bioisosteres of the carboxylic acid group (2-7) were synthesized and tested. Most of the synthesized compounds showed substrate activities with GABA-AT; 1H-tetrazole-5-propanamine (6) was the best of those tested. Th...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yuan H,Silverman RB

    更新日期:2006-03-01 00:00:00

  • Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111.

    abstract::We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1-4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1-4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Matsushita K,Nakata T,Takeda-Okuda N,Nadanaka S,Kitagawa H,Tamura JI

    更新日期:2018-03-01 00:00:00

  • Phenylimidazole derivatives as specific inhibitors of bacterial enoyl-acyl carrier protein reductase FabK.

    abstract::Bacterial enoyl-acyl carrier protein (ACP) reductases (FabI and FabK) catalyze the final step in each cycle of bacterial fatty acid biosynthesis and are attractive targets for the development of new antibacterial agents. Here, we report the development of novel FabK inhibitors with antibacterial activity against Strep...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ozawa T,Kitagawa H,Yamamoto Y,Takahata S,Iida M,Osaki Y,Yamada K

    更新日期:2007-12-01 00:00:00

  • Synthesis of indomethacin analogues for evaluation as modulators of MRP activity.

    abstract::Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Maguire AR,Plunkett SJ,Papot S,Clynes M,O'Connor R,Touhey S

    更新日期:2001-03-01 00:00:00

  • 2D QSAR and similarity studies on cruzain inhibitors aimed at improving selectivity over cathepsin L.

    abstract::Hologram quantitative structure-activity relationships (HQSAR) were applied to a data set of 41 cruzain inhibitors. The best HQSAR model (Q(2)=0.77; R(2)=0.90) employing Surflex-Sim, as training and test sets generator, was obtained using atoms, bonds, and connections as fragment distinctions and 4-7 as fragment size....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Freitas RF,Oprea TI,Montanari CA

    更新日期:2008-01-15 00:00:00

  • Novel DNA-directed alkylating agents: design, synthesis and potent antitumor effect of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker.

    abstract::A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies r...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kapuriya N,Kapuriya K,Dong H,Zhang X,Chou TC,Chen YT,Lee TC,Lee WC,Tsai TH,Naliapara Y,Su TL

    更新日期:2009-02-01 00:00:00