Novel sulfonamides as potential, systemically active antitumor agents

Yoshino, Hiroshi; Ueda, Norihiro; Niijima, Jun; Sugumi, Hiroyuki; Kotake, Yoshihiko; Koyanagi, Nozomu; Yoshimatsu, Kentaro; Asada, Makoto; Watanabe, Tatsuo; Nagasu, Takeshi; Tsukahara, Kappei; Iijima, Atsumi; Kitoh, Kyosuke

doi:10.1021/jm00091a018

Cited by 217 publications

(152 citation statements)

References 8 publications

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“…TN16 was purchased from Calbiochem. The bromo-derivative of ABT751 was synthesized according to the chemical route reported for the preparation of ABT751 and its analogs, using at the final step p-bromobenzenesulfonyl chloride instead of p-methoxybenzenesufonyl chloride for ABT751 (28).…”

Section: Methodsmentioning

confidence: 99%

Variations in the colchicine-binding domain provide insight into the structural switch of tubulin

Dorléans

Gigant

Ravelli

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

246

285

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Structural changes occur in the ␣␤-tubulin heterodimer during the microtubule assembly/disassembly cycle. Their most prominent feature is a transition from a straight, microtubular structure to a curved structure. There is a broad range of small molecule compounds that disturbs the microtubule cycle, a class of which targets the colchicine-binding site and prevents microtubule assembly. This class includes compounds with very different chemical structures, and it is presently unknown whether they prevent tubulin polymerization by the same mechanism. To address this issue, we have determined the structures of tubulin complexed with a set of such ligands and show that they interfere with several of the movements of tubulin subunits structural elements upon its transition from curved to straight. We also determined the structure of tubulin unliganded at the colchicine site; this reveals that a ␤-tubulin loop (termed T7) flips into this site. As with colchicine site ligands, this prevents a helix which is at the interface with ␣-tubulin from stacking onto a ␤-tubulin ␤ sheet as in straight protofilaments. Whereas in the presence of these ligands the interference with microtubule assembly gets frozen, by flipping in and out the ␤-subunit T7 loop participates in a reversible way in the resistance to straightening that opposes microtubule assembly. Our results suggest that it thereby contributes to microtubule dynamic instability.cytoskeleton ͉ inhibitors ͉ microtubules

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Section: Methodsmentioning

confidence: 99%

Variations in the colchicine-binding domain provide insight into the structural switch of tubulin

Dorléans

Gigant

Ravelli

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

246

285

View full text Add to dashboard Cite

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“…Anti-inflammatory, analgesic, and antipyretic activities for some thiazolyl and benzothiazolyl derivatives are also known. 7,8 On the other hand, sulfonamides have a variety of biological activities such as antibacterial, [9][10][11] insulin releasing, 12 carbonic anhydrase inhibitory, 13,14 anti-inflammatory, 15 and antitumor 16 activities. These findings encouraged us to explore the synthesis of sulfonamides containing thiazole/benzothiazole moieties and to examine their antibacterial and antifungal properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of sulfonamide thiazole and benzothiazole derivatives as antimicrobial agents

Argyropoulou¹,

Geronikaki²,

Vicini³

et al. 2009

Arkivoc

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Dedicated to 80 th anniversary of Prof. Henk Van der PlasAbstract Several thiazoles and benzothiazoles carrying a benzenesulfonamide moiety at position 2 of the heterocyclic nucleus were synthesised and tested as antimicrobial agents. All sulfanilamides and some of the nitro substituted sulfonamides have effective antibacterial properties against Gram positive bacteria (MIC 0.3-100 µg/mL) such as several bacilli, staphylococci and streptococci, including methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis strains. On the contrary, no inhibition of Gram negative Escherichia coli and fungi is detected up to the concentration of 100 µg/mL. Synergistic inhibitory activity occurs when the active antibacterial sulfonamides are tested in combination with trimethoprim against both Bacillus subtilis and Staphylococcus aureus.

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“…The antitumor activity is mediated by cytotoxicity, via polo-like kinase disturbance, and by MDR1 down-regulation, via binding to the B-subunit of the essential transcription factor NF-Y (Tanaka et al, 2003). Two other sulfonamides, E7070 and E7010, are regarded as breakthroughs in the discovery of new sulfonamides with strong antineoplastic ability (Yoshino et al, 1992;Owa et al, 1999). E7070 is in a class of novel cell cycle inhibitors that block cell cycle progression at multiple points, although its target mechanism remains unclear (Van Kesteren et al, 2002).…”

mentioning

confidence: 99%

A Novel Oral Indoline-Sulfonamide Agent, N-[1-(4-Methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-Isonicotinamide (J30), Exhibits Potent Activity against Human Cancer Cells in Vitro and in Vivo through the Disruption of Microtubule

Liou

Hsu

Kuo

et al. 2007

J Pharmacol Exp Ther

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We have previously synthesized a series of 7-aroylaminoindoline-1-sulfonamides as a novel class of antitubulin agents. Here we show that one of these new compounds, N-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-isonicotinamide (J30), is potently effective against various resistant and nonresistant cancer cell lines despite the status of multidrug resistance, multidrug-resistance associated protein, or other resistance factors in vitro. J30 inhibits assembly of purified tubulin by strongly binding to the colchicine-binding site. Western blot and immunofluorescence experiments demonstrate that J30 depolymerizes microtubules in the KB cell line, resulting in an accumulation of G 2 /M phase cells. Further studies indicate that J30 causes cell cycle arrest, as assessed by flow analyses and the appearance of MPM-2 (a specific mitotic marker), and is associated with up-regulation of cyclin B1, phosphorylation of Cdc25C, and dephosphorylation of Cdc2. J30 also causes Bcl-2 phosphorylation, cytochrome c translocation, and activation of the caspase-9 and caspase-3 cascades. These findings suggest that the J30-mediated apoptotic signaling pathway depends on caspases and mitochondria. Finally, we show that oral administration of J30 significantly inhibits tumor growth in NOD/scid mice bearing human oral, gastric, and drug-resistant xenografts. Together, our results suggest that J30 has potential as a chemotherapeutic agent for treatment of various malignancies.One of the most successful classes of antitumor drugs targets microtubules, the principal components of the cytoskeleton that are important in cell division, organelle transport, cytokinesis, maintenance of cell morphology, and signal transduction (Jordan and Wilson, 2004). There are two categories of antitubulin compounds used to target highly proliferating malignant cells. The microtubule depolymerizing agents, such as vinca alkaloids and colchicinoids, inhibit tubulin polymerization. The microtubule polymerizing agents, such as taxanes and epothilones, promote or stabilize the tubulin polymer form (Pellegrini and Budman, 2005). Recent studies suggest that the inhibitory effects of these drugs are due to their interruption of microtubule dynamics rather than to alteration of microtubule polymer mass. The disruption of microtubule dynamics leads to arrest of growing cells in metaphase/anaphase, causing apoptotic cell death or nonapoptotic slow cell death (Mollinedo and Gajate, 2003).Taxanes and vinca alkaloids have been in clinical use for a long time, but these drugs have many drawbacks (Attard et al., 2006). First, drug resistance, caused by mutations and/or This work was supported in part by grants from National Health Research Institutes, Taipei, Taiwan (NHRI Intramural Grant CA-095-PP-04), and the National Science Council, Taipei, Taiwan (NSC 95-2752-B-400-001-PAE).J.P.L. and K.S.H. contributed equally to this work. Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.107.126680....

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Novel sulfonamides as potential, systemically active antitumor agents

Cited by 217 publications

References 8 publications

Variations in the colchicine-binding domain provide insight into the structural switch of tubulin

Variations in the colchicine-binding domain provide insight into the structural switch of tubulin

Synthesis and biological evaluation of sulfonamide thiazole and benzothiazole derivatives as antimicrobial agents

A Novel Oral Indoline-Sulfonamide Agent, N-[1-(4-Methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-Isonicotinamide (J30), Exhibits Potent Activity against Human Cancer Cells in Vitro and in Vivo through the Disruption of Microtubule

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