antimitotic agents

Summary

Summary: Agents that arrest cells in MITOSIS, most notably TUBULIN MODULATORS.

Top Publications

  1. Gascoigne K, Taylor S. How do anti-mitotic drugs kill cancer cells?. J Cell Sci. 2009;122:2579-85 pubmed publisher
    ..In this Commentary, we outline recent advances in our understanding of how cancer cells respond to anti-mitotic drugs, and discuss the relevance of these studies to their use in the clinic. ..
  2. Stander A, Joubert F, Joubert A. Docking, synthesis, and in vitro evaluation of antimitotic estrone analogs. Chem Biol Drug Des. 2011;77:173-81 pubmed publisher
  3. Kamal A, Balakishan G, Ramakrishna G, Shaik T, Sreekanth K, Balakrishna M, et al. Synthesis and biological evaluation of cinnamido linked pyrrolo[2,1-c][1,4]benzodiazepines as antimitotic agents. Eur J Med Chem. 2010;45:3870-84 pubmed publisher
    ..Interestingly, compounds 5b and 6b have been identified as a new class of inhibitors of tubulin polymerization and their action has been rationalized by the cell cycle arrest in G0 and G2/M phase. ..
  4. Nagle A, Hur W, Gray N. Antimitotic agents of natural origin. Curr Drug Targets. 2006;7:305-26 pubmed
    b>Antimitotic agents have been the most successful pharmacological agents for the treatment of cancer...
  5. Huang H, Shi J, Orth J, Mitchison T. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell. 2009;16:347-58 pubmed publisher
    ..We conclude targeting Cdc20, or otherwise blocking mitotic exit, may be a better cancer therapeutic strategy than perturbing spindle assembly. ..
  6. Orth J, Tang Y, Shi J, Loy C, Amendt C, Wilm C, et al. Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate. Mol Cancer Ther. 2008;7:3480-9 pubmed publisher
    ..Our analysis shows that K5Is cause cancer-selective cell killing, provides important kinetic information for understanding clinical responses, and elucidates mechanisms of drug sensitivity versus resistance at the level of phenotype. ..
  7. Saijo T, Ishii G, Ochiai A, Yoh K, Goto K, Nagai K, et al. Eg5 expression is closely correlated with the response of advanced non-small cell lung cancer to antimitotic agents combined with platinum chemotherapy. Lung Cancer. 2006;54:217-25 pubmed
    ..We also investigated cyclin B1 expression, which is involved in the G2/M transition. All patients received antimitotic agents combined with platinum chemotherapy...
  8. Hu L, Li Z, Li Y, Qu J, Ling Y, Jiang J, et al. Synthesis and structure-activity relationships of carbazole sulfonamides as a novel class of antimitotic agents against solid tumors. J Med Chem. 2006;49:6273-82 pubmed
    ..Also, the SAR information gleaned from ring A-substituted analogues varies significantly from that of 1. Carbazole sulfonamides are a novel promising class of antimitotic agents with clinical development potential.
  9. Kiselyov A, Balakin K, Tkachenko S, Savchuk N, Ivachtchenko A. Recent progress in discovery and development of antimitotic agents. Anticancer Agents Med Chem. 2007;7:189-208 pubmed
    This review highlights structural diversity of antimitotic agents. In particular, we emphasized current antimitotic therapies based on modulation of microtubule dynamics...

More Information

Publications62

  1. Vogel S, Kaufmann D, Pojarova M, Muller C, Pfaller T, Kühne S, et al. Aroyl hydrazones of 2-phenylindole-3-carbaldehydes as novel antimitotic agents. Bioorg Med Chem. 2008;16:6436-47 pubmed publisher
    ..Since these 2-phenylindole-based hydrazones display no structural similarity with other antitumor drugs they are interesting candidates for further development. ..
  2. Komlodi Pasztor E, Sackett D, Wilkerson J, Fojo T. Mitosis is not a key target of microtubule agents in patient tumors. Nat Rev Clin Oncol. 2011;8:244-50 pubmed publisher
    ..While mitosis-specific inhibitors are effective on only a small fraction of the tumor mass (dividing cells), MTAs target tubulin, a protein that has crucial roles in both mitotic and non-mitotic cells. ..
  3. Hamze A, Giraud A, Messaoudi S, Provot O, Peyrat J, Bignon J, et al. Synthesis, biological evaluation of 1,1-diarylethylenes as a novel class of antimitotic agents. ChemMedChem. 2009;4:1912-24 pubmed publisher
    ..Both compounds 2 k and 2 s have the potential for further prodrug modification and development as vascular disrupting agents for treatment of solid tumors. ..
  4. Ducki S. Antimitotic chalcones and related compounds as inhibitors of tubulin assembly. Anticancer Agents Med Chem. 2009;9:336-47 pubmed
    The development of chalcones as antimitotic agents has led to the design of other analogues able to interact with tubulin and inhibit its assembly into microtubules. This activity has also been associated with their anti-vascular activity...
  5. Gascoigne K, Taylor S. Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell. 2008;14:111-22 pubmed publisher
    ..We present data supporting a model wherein cell fate is dictated by two competing networks, one involving caspase activation, the other protecting cyclin B1 from degradation...
  6. Shi J, Orth J, Mitchison T. Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5. Cancer Res. 2008;68:3269-76 pubmed publisher
  7. Ouyang X, Piatnitski E, Pattaropong V, Chen X, He H, Kiselyov A, et al. Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg Med Chem Lett. 2006;16:1191-6 pubmed
    ..for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents.
  8. Brier S, Lemaire D, DeBonis S, Forest E, Kozielski F. Molecular dissection of the inhibitor binding pocket of mitotic kinesin Eg5 reveals mutants that confer resistance to antimitotic agents. J Mol Biol. 2006;360:360-76 pubmed
    ..These results suggest that tumour cells might develop resistance to Eg5 inhibitors, by expressing Eg5 point mutants that retain the enzyme activity, but prevent inhibition, a feature that is observed for certain tubulin inhibitors. ..
  9. Magnani M, Ortuso F, Soro S, Alcaro S, Tramontano A, Botta M. The betaI/betaIII-tubulin isoforms and their complexes with antimitotic agents. Docking and molecular dynamics studies. FEBS J. 2006;273:3301-10 pubmed
    ..In this paper, we analyze the binding modes of these antimitotic agents to type I and III isoforms of beta-tubulin by computational methods...
  10. Topham C, Taylor S. Mitosis and apoptosis: how is the balance set?. Curr Opin Cell Biol. 2013;25:780-5 pubmed publisher
    ..This in turn may open up new opportunities to sensitize cancer cells to anti-mitotic agents. ..
  11. Chen W, Seefeldt T, Young A, Zhang X, Zhao Y, RUFFOLO J, et al. Microtubule S-glutathionylation as a potential approach for antimitotic agents. BMC Cancer. 2012;12:245 pubmed publisher
    ..Microtubule-targeting drugs are, therefore, referred to as antimitotic agents. However, the clinical application of the current antimitotic drugs is hampered by emerging drug resistance ..
  12. Mohan R, Banerjee M, Ray A, Manna T, Wilson L, Owa T, et al. Antimitotic sulfonamides inhibit microtubule assembly dynamics and cancer cell proliferation. Biochemistry. 2006;45:5440-9 pubmed
  13. O Neill M, Mayer M, Murray K, Rolim Santos H, Santos Magalhães N, Thompson A, et al. Does usnic acid affect microtubules in human cancer cells?. Braz J Biol. 2010;70:659-64 pubmed
    ..These results suggest that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilisation of microtubules. ..
  14. Rudek M, Zhao M, He P, Messersmith W, Baker S. Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate ABT-751, ABT-751 glucuronide, and ABT-751 sulfate in human plasma for clinical pharmacology studies. J Pharm Biomed Anal. 2006;42:253-60 pubmed
    ..A 20,000 ng/ml sample that was diluted 1:10 (v/v) with plasma was accurately quantitated. The method has been successfully applied to study the plasma pharmacokinetics of ABT-751 in humans. ..
  15. Choi M, No E, Thorat D, Jang J, Yang H, Lee J, et al. Synthesis and biological evaluation of aryloxazole derivatives as antimitotic and vascular-disrupting agents for cancer therapy. J Med Chem. 2013;56:9008-18 pubmed publisher
    ..We believe that compound 6-48 will serve as a good lead compound for antimitotic and vascular-disrupting agents; further investigation to improve the in vivo efficacy of this series is underway. ..
  16. Nguyen T, Lomberget T, Tran N, Colomb E, Nachtergaele L, Thoret S, et al. Synthesis and biological evaluation of novel heterocyclic derivatives of combretastatin A-4. Bioorg Med Chem Lett. 2012;22:7227-31 pubmed publisher
  17. Nishiguchi G, Graham J, Bouraoui A, Jacobs R, Little R. 7,11-epi-thyrsiferol: completion of its synthesis, evaluation of its antimitotic properties, and the further development of an SAR model. J Org Chem. 2006;71:5936-41 pubmed
  18. Ngo Q, Roussi F, Cormier A, Thoret S, Knossow M, Guenard D, et al. Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids. J Med Chem. 2009;52:134-42 pubmed publisher
    ..These interesting biological activities may eventually be explained by the fact that their lateral chain resides in a pocket distinct from that of the phomopsin A peptide, at the interface of tubulins beta and alpha. ..
  19. Harrison M, Holen K, Liu G. Beyond taxanes: a review of novel agents that target mitotic tubulin and microtubules, kinases, and kinesins. Clin Adv Hematol Oncol. 2009;7:54-64 pubmed
    ..This review will concentrate on novel agents in later clinical development that target both the spindle microtubule and nonmicrotubule constituents of mitosis. ..
  20. Lazo J. In the forefront of basic and translational cancer research - 7th AACR-JCA Joint International Conference. IDrugs. 2007;10:224-6 pubmed
  21. Salmela A, Pouwels J, Kukkonen Macchi A, Waris S, Toivonen P, Jaakkola K, et al. The flavonoid eupatorin inactivates the mitotic checkpoint leading to polyploidy and apoptosis. Exp Cell Res. 2012;318:578-92 pubmed publisher
    ..Finally, eupatorin potently induces apoptosis in multiple cancer cell lines and suppresses cancer cell proliferation in organotypic 3D cell culture model. ..
  22. Arayne M, Sultana N. Porous nanoparticles in drug delivery systems. Pak J Pharm Sci. 2006;19:158-69 pubmed
    ..This article will highlight rational approaches in design and surface engineering of nanoscale vehicles and entities for site-specific drug delivery. Potential pitfalls or side effects associated with nanoparticles are also discussed. ..
  23. Romagnoli R, Baraldi P, Sarkar T, Carrion M, Cara C, Cruz Lopez O, et al. Synthesis and biological evaluation of 1-methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a new class of antimitotic agents and tubulin inhibitors. J Med Chem. 2008;51:1464-8 pubmed publisher
    ..We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent antiproliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death. ..
  24. Jordan M, Kamath K. How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007;7:730-42 pubmed
  25. Paterson I, Naylor G, Gardner N, Guzman E, Wright A. Total synthesis and biological evaluation of a series of macrocyclic hybrids and analogues of the antimitotic natural products dictyostatin, discodermolide, and taxol. Chem Asian J. 2011;6:459-73 pubmed publisher
    ..This led to the identification of a potent macrocyclic discodermolide/dictyostatin hybrid 12 and its C9 methoxy derivative 38, accessible by an efficient total synthesis and with a similar biological profile to dictyostatin. ..
  26. Holland J, Kang A, Cohrs S, Selivanova S, Milicevic Sephton S, Betzel T, et al. Synthesis and evaluation of biphenyl compounds as kinesin spindle protein inhibitors. Chem Biodivers. 2013;10:538-55 pubmed publisher
    ..we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression...
  27. Abramov Y, Carmi S, Anteby S, Ringel I. Ex vivo 1H and 31P magnetic resonance spectroscopy as a means for tumor characterization in ovarian cancer patients. Oncol Rep. 2013;29:321-8 pubmed publisher
    ..The 31P-MRS technique allowed characterization and monitoring of metabolic changes occurring in ovarian cancer cells in response to chemotherapy. ..
  28. Scherlach K, Brendel N, Ishida K, Dahse H, Hertweck C. Photochemical oxazole-nitrile conversion downstream of rhizoxin biosynthesis and its impact on antimitotic activity. Org Biomol Chem. 2012;10:5756-9 pubmed publisher
    ..These results highlight the impact of photoreactions onto the antiproliferative agent and encourage the introduction of bioisosteric groups that render the compound less susceptible towards photooxidation. ..
  29. Stander B, Joubert F, Tu C, Sippel K, McKenna R, Joubert A. In vitro evaluation of ESE-15-ol, an estradiol analogue with nanomolar antimitotic and carbonic anhydrase inhibitory activity. PLoS ONE. 2012;7:e52205 pubmed publisher
  30. Kollareddy M, Sherrard A, Park J, Szemes M, Gallacher K, Melegh Z, et al. The small molecule inhibitor YK-4-279 disrupts mitotic progression of neuroblastoma cells, overcomes drug resistance and synergizes with inhibitors of mitosis. Cancer Lett. 2017;403:74-85 pubmed publisher
    ..Thus, YK-4-279 could potentially be used as a single-agent or in combination therapies for the treatment of high-risk and relapsing neuroblastoma, as well as other cancers. ..
  31. Kumar G, Nayak V, Sayeed I, Reddy V, Shaik A, Mahesh R, et al. Design, synthesis of phenstatin/isocombretastatin-oxindole conjugates as antimitotic agents. Bioorg Med Chem. 2016;24:1729-40 pubmed publisher
    ..23 μM and 1.01 μM, respectively. Molecular docking studies indicated that these compounds (5c and 5d) occupy the colchicine binding site of the tubulin. ..
  32. Ahn S, Duke C, Barrett C, Hwang D, Li C, Miller D, et al. I-387, a novel antimitotic indole, displays a potent in vitro and in vivo antitumor activity with less neurotoxicity. Mol Cancer Ther. 2010;9:2859-68 pubmed publisher
    ..The potent in vitro and in vivo antitumor activity of I-387 suggests that it may represent a new antimitotic agent for management of various malignancies, particularly for patients with drug-resistant cancer. ..
  33. Chen Y, Huang C, Huang Z, Tseng C, Chang F, Yang S, et al. Synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives. Bioorg Med Chem. 2006;14:3098-105 pubmed
    ..This result is interesting because 2-phenylquinolone derivatives have been reported to be antimitotic agents which induced cell cycle arrest in G2/M phase.
  34. McCubbin J, Maddess M, Lautens M. Total synthesis of cryptophycin analogues via a scaffold approach. Org Lett. 2006;8:2993-6 pubmed
    ..Three scaffolds are prepared in gram quantities by a ring-closing metathesis approach. Derivatization via a variety of cross-coupling protocols is possible, which affords novel analogues of these potent antimitotic agents.
  35. Whang Y, Park K, Jung H, Jo U, Kim Y. Microtubule-damaging agents enhance RASSF1A-induced cell death in lung cancer cell lines. Cancer. 2009;115:1253-66 pubmed publisher
    ..RSAAF1A protein has a cooperative growth inhibitory effect with microtubule-targeted drugs through cyclin B1 accumulation on NSCLC cells, suggesting novel insights for the selection of chemotherapeutic agents. ..
  36. García Álvarez I, Garrido L, Doncel Perez E, Nieto Sampedro M, Fernandez Mayoralas A. Detection of metabolite changes in C6 glioma cells cultured with antimitotic oleyl glycoside by 1H MAS NMR. J Med Chem. 2009;52:1263-7 pubmed publisher
    ..These results point to NMR spectroscopy as an efficient technique for monitoring the response of the cells to therapeutic agents. ..
  37. Rossio V, Galati E, Piatti S. Adapt or die: how eukaryotic cells respond to prolonged activation of the spindle assembly checkpoint. Biochem Soc Trans. 2010;38:1645-9 pubmed publisher
    ..Inhibition of factors involved in SAC adaptation could have important therapeutic applications by potentiating the ability of antimitotics to cause cell death. ..
  38. López Donaire M, Parra Cáceres J, Fernandez Gutierrez M, Vázquez Lasa B, Roman J. Polymeric drugs based on random copolymers with antimitotic activity. Biomacromolecules. 2010;11:2478-86 pubmed publisher
    ..The polymeric drugs with 30 and 50 mol % OAGMA presented antimitotic activity on a human glioblastoma line, but they were less toxic on normal human fibroblast cultures. ..
  39. Rao P, Cessac J, Boyd J, Hanson A, Shah J. Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs. Part III. Steroids. 2008;73:171-83 pubmed
    ..Of nine analogs synthesized, five have demonstrated superior antiproliferative activities compared to 2-methoxyestradiol. ..
  40. Hung C, Lin Y, Liu L, Kuo S, Ho C, Way T. CWF-145, a novel synthetic quinolone derivative exerts potent antimitotic activity against human prostate cancer: Rapamycin enhances antimitotic drug-induced apoptosis through the inhibition of Akt/mTOR pathway. Chem Biol Interact. 2016;260:1-12 pubmed publisher
    ..We found that CWF-145 had a similar effect to clinical trial antimitotic agents in cancer cells and normal cells...
  41. Wipf P, Graham T, Vogt A, Sikorski R, Ducruet A, Lazo J. Cellular analysis of disorazole C and structure-activity relationship of analogs of the natural product. Chem Biol Drug Des. 2006;67:66-73 pubmed
    ..We conclude that disorazole C(1) is a potent inducer of mitotic arrest and hypothesize that this biological activity may be mediated by microtubule perturbation. ..
  42. Thamkachy R, Kumar R, Rajasekharan K, Sengupta S. ERK mediated upregulation of death receptor 5 overcomes the lack of p53 functionality in the diaminothiazole DAT1 induced apoptosis in colon cancer models: efficiency of DAT1 in Ras-Raf mutated cells. Mol Cancer. 2016;15:22 pubmed publisher
    ..Besides, efficiency in cancer cells with mutations in the Ras oncoprotein or its downstream kinase Raf raise interest in diaminothiazole class of compounds for further follow-up. ..
  43. Labrière C, Talapatra S, Thoret S, Bougeret C, Kozielski F, Guillou C. New MKLP-2 inhibitors in the paprotrain series: Design, synthesis and biological evaluations. Bioorg Med Chem. 2016;24:721-34 pubmed publisher
    ..Increased selectivity and higher potency is therefore a step forward toward establishing MKLP-2 as a potential cancer drug target. ..
  44. Rodríguez Agirretxe I, Vega S, Rezola R, Vecino E, Mendicute J, Suarez Cortes T, et al. The PLGA implant as an antimitotic delivery system after experimental trabeculectomy. Invest Ophthalmol Vis Sci. 2013;54:5227-35 pubmed publisher
    ..MMC-loaded and -coated implants have optimal surgical results, followed by topical MMC application. In this experimental model, bevacizumab could interact with MMC. ..
  45. Kantarjian H, Padmanabhan S, Stock W, Tallman M, Curt G, Li J, et al. Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia. Invest New Drugs. 2012;30:1107-15 pubmed publisher
    ..Evidence of monoasters in all but the 4 mg/day dose group provided proof of mechanism for AZD4877. This study was terminated due to lack of efficacy. (ClinicalTrials.gov identifier NCT00486265). ..
  46. Gustafsson K, Wang X, Severa D, Eriksson M, Kimby E, Merup M, et al. Expression of cannabinoid receptors type 1 and type 2 in non-Hodgkin lymphoma: growth inhibition by receptor activation. Int J Cancer. 2008;123:1025-33 pubmed publisher
    ..Together, our results suggest that therapies using cannabinoid receptor ligands will have efficiency in reducing tumor burden in malignant lymphoma overexpressing CB1 and CB2. ..
  47. Leslie B, Holaday C, Nguyen T, Hergenrother P. Phenylcinnamides as novel antimitotic agents. J Med Chem. 2010;53:3964-72 pubmed publisher
    ..exclusion of compounds from the central nervous system, 8H and its derivatives merit further examination as potential antimitotic therapeutics, specifically for brain cancers and cancers that are resistant to standard antimitotic agents.
  48. Lee H, Chang J, Chang L, Lai W, Lai M, Shih K, et al. Concise syntheses of N-aryl-5,6,7-trimethoxyindoles as antimitotic and vascular disrupting agents: application of the copper-mediated Ullmann-type arylation. Org Biomol Chem. 2011;9:3154-7 pubmed publisher
    ..These synthesized compounds demonstrated potent antiproliferative activity providing a novel skeleton for potent tubulin polymerization inhibitors. ..
  49. Matson D, Stukenberg P. Spindle poisons and cell fate: a tale of two pathways. Mol Interv. 2011;11:141-50 pubmed publisher
    ..Emerging from these studies is not only a greater understanding of how these classic antimitotic agents bring about cell death, but also a wealth of potential new targets of anticancer therapeutics.
  50. Lee S, Kim M, Lim J, Kim Y, Han K, Kim S, et al. [A case of therapy-related acute myeloid leukemia associated with inv(16)]. Korean J Lab Med. 2007;27:19-21 pubmed
    ..Herein, we report a case of t-AML with inv(16) after combination chemotherapy using antimitotic agent and alkylating agent (cis-platin-paclitaxel) for ovarian serous cystadenocarcinoma. ..
  51. Polak M, Valamanesh F, Felt O, Torriglia A, Jeanny J, Bourges J, et al. Controlled delivery of 5-chlorouracil using poly(ortho esters) in filtering surgery for glaucoma. Invest Ophthalmol Vis Sci. 2008;49:2993-3003 pubmed publisher
    ..Thus, the slow release of POE/5-CU may be beneficial for the prevention of bleb closure in patients who undergo complicated trabeculectomy. ..
  52. Baptistella E, Malafaia O, Czeczko N, Ribas Filho J, Nassif P, Nascimento M, et al. Comparative study in swines' vocal cords healing after excision of fragment with CO2 laser with mitomycin and 5-fluorouracil postoperative topical application. Acta Cir Bras. 2009;24:13-8 pubmed
    ..Mitomycin and 5-fluorouracil had promoted beneficial change in vocal fold's cicatrization with less collagen deposition, but there was no significant statistically difference when they were compared between themselves. ..
  53. Rieder C, Medema R. No way out for tumor cells. Cancer Cell. 2009;16:274-5 pubmed publisher
    ..Although this is not an unexpected finding, it nevertheless provides a novel conceptual framework for augmenting the antimitotic strategies currently under development for fighting cancer. ..