Pharmaceutical Research

, Volume 29, Issue 11, pp 2943–2971 | Cite as

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

  • Yan Lu
  • Jianjun Chen
  • Min Xiao
  • Wei Li
  • Duane D. MillerEmail author
Expert Review


Tubulin dynamics is a promising target for new chemotherapeutic agents. The colchicine binding site is one of the most important pockets for potential tubulin polymerization destabilizers. Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation. A large number of molecules interacting with the colchicine binding site have been designed and synthesized with significant structural diversity. CBSIs have been modified as to chemical structure as well as pharmacokinetic properties, and tested in order to find a highly potent, low toxicity agent for treatment of cancers. CBSIs are believed to act by a common mechanism via binding to the colchicine site on tubulin. The present review is a synopsis of compounds that have been reported in the past decade that have provided an increase in our understanding of the actions of CBSIs.


antimitotic cancer colchicine multidrug resistance tubulin polymerization inhibitor 





ATP binding cassette


binding site


combretastatin A-4


colchicine binding site inhibitors


cyclic guanosine monophosphate


central nervous system


comparative molecular field analyses


comparative molecular similarity indices analyses


N-deacetyl-N-(2-mercaptoacetyl) colchicine


Food and Drug Administration


fibroblast growth factor


hypoxia-inducible factor


human umbilical vein endothelial cell


linear interaction energy


multidrug resistance


multidrug resistance-associated protein


microtubule targeting agent


National Cancer Institute








quantitative structure-activity relationships


structure-activity relationship


surface-generalized Born




tumor necrosis factor-α


vascular-disrupting agent


vascular endothelial growth factor receptor


Acknowledgments & Disclosures

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA148706. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional supports were provided by the Van Vleet Endowed Professorship.


  1. 1.
    Pryor DE, O'Brate A, Bilcer G, Diaz JF, Wang Y, Kabaki M, et al. The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry. 2002;41:9109–15.PubMedGoogle Scholar
  2. 2.
    Gigant B, Wang C, Ravelli RB, Roussi F, Steinmetz MO, Curmi PA, et al. Structural basis for the regulation of tubulin by vinblastine. Nature. 2005;435:519–22.PubMedGoogle Scholar
  3. 3.
    Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004;428:198–202.PubMedGoogle Scholar
  4. 4.
    Seveand P, Dumontet C. Is class III beta-tubulin a predictive factor in patients receiving tubulin-binding agents? The Lancet Oncology. 2008;9:168–75.Google Scholar
  5. 5.
    Stengel C, Newman SP, Leese MP, Potter BV, Reed MJ, Purohit A. Class III beta-tubulin expression and in vitro resistance to microtubule targeting agents. Br J Cancer. 2010;102:316–24.PubMedGoogle Scholar
  6. 6.
    Goto H, Yano S, Zhang H, Matsumori Y, Ogawa H, Blakey DC, et al. Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice. Cancer Res. 2002;62:3711–5.PubMedGoogle Scholar
  7. 7.
    Lippert 3rd JW. Vascular disrupting agents. Bioorg Med Chem. 2007;15:605–15.PubMedGoogle Scholar
  8. 8.
    Rustin GJ, Shreeves G, Nathan PD, Gaya A, Ganesan TS, Wang D, et al. A Phase Ib trial of CA4P (combretastatin A-4 phosphate), carboplatin, and paclitaxel in patients with advanced cancer. Br J Cancer. 2010;102:1355–60.PubMedGoogle Scholar
  9. 9.
    Kim TJ, Ravoori M, Landen CN, Kamat AA, Han LY, Lu C, et al. Antitumor and antivascular effects of AVE8062 in ovarian carcinoma. Cancer Res. 2007;67:9337–45.PubMedGoogle Scholar
  10. 10.
  11. 11.
    Pettit GR, Toki B, Herald DL, Verdier-Pinard P, Boyd MR, Hamel E, et al. Antineoplastic agents. 379. Synthesis of phenstatin phosphate. J Med Chem. 1998;41:1688–95.PubMedGoogle Scholar
  12. 12.
    Zhang LH, Wu L, Raymon HK, Chen RS, Corral L, Shirley MA, et al. The synthetic compound CC-5079 is a potent inhibitor of tubulin polymerization and tumor necrosis factor-alpha production with antitumor activity. Cancer Res. 2006;66:951–9.PubMedGoogle Scholar
  13. 13.
    Bohlinand L, Rosen B. Podophyllotoxin derivatives: drug discovery and development. Drug Discov Today. 1996;1:343–51.Google Scholar
  14. 14.
    Kupchan SM, Britton RW, Ziegler MF, Gilmore CJ, Restivo RJ, Bryan RF. Steganacin and steganangin, novel antileukemic lignan lactones from Steganotaenia araliacea. J Am Chem Soc. 1973;95:1335–6.PubMedGoogle Scholar
  15. 15.
    Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. Journal of Applied Toxicology: JAT 2011. doi: 10.1002/jat.1753
  16. 16.
    Hamel E. Antimitotic natural products and their interactions with tubulin. Medicinal Research Reviews. 1996;16:207–31.PubMedGoogle Scholar
  17. 17.
    Matei D, Schilder J, Sutton G, Perkins S, Breen T, Quon C, et al. Activity of 2 methoxyestradiol (Panzem NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: a Hoosier Oncology Group trial. Gynecol Oncol. 2009;115:90–6.PubMedGoogle Scholar
  18. 18.
    LaVallee TM, Burke PA, Swartz GM, Hamel E, Agoston GE, Shah J, et al. Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198. Mol Cancer Ther. 2008;7:1472–82.PubMedGoogle Scholar
  19. 19.
    Pasquier E, Sinnappan S, Munoz MA, Kavallaris M. ENMD-1198, a new analogue of 2-methoxyestradiol, displays both antiangiogenic and vascular-disrupting properties. Mol Cancer Ther. 2010;9:1408–18.PubMedGoogle Scholar
  20. 20.
    Hande KR, Hagey A, Berlin J, Cai Y, Meek K, Kobayashi H, et al. The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: results of a phase 1 study. Clin Cancer Res. 2006;12:2834–40.PubMedGoogle Scholar
  21. 21.
    Shan B, Medina JC, Santha E, Frankmoelle WP, Chou TC, Learned RM, et al. Selective, covalent modification of beta-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors. Proc Natl Acad Sci U S A. 1999;96:5686–91.PubMedGoogle Scholar
  22. 22.
    Patterson DM, Rustin GJS, Serradell N, Rosa E, Bolos J. Combretastatin A-4 phosphate. Drugs of the Future. 2007;32:1025–32.Google Scholar
  23. 23.
    Rischin D, Bibby DC, Chong G, Kremmidiotis G, Leske AF, Matthews CA, et al. Clinical, pharmacodynamic, and pharmacokinetic evaluation of BNC105P: a phase I trial of a novel vascular disrupting agent and inhibitor of cancer cell proliferation. Clin Cancer Res. 2011;17:5152–60.PubMedGoogle Scholar
  24. 24.
    Bacher G, Nickel B, Emig P, Vanhoefer U, Seeber S, Shandra A, et al. D-24851, a novel synthetic microtubule inhibitor, exerts curative antitumoral activity in vivo, shows efficacy toward multidrug-resistant tumor cells, and lacks neurotoxicity. Cancer Res. 2001;61:392–9.PubMedGoogle Scholar
  25. 25.
    Gourdeau H, Leblond L, Hamelin B, Desputeau C, Dong K, Kianicka I, et al. Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents. Mol Cancer Ther. 2004;3:1375–84.PubMedGoogle Scholar
  26. 26.
    Sirisoma N, Kasibhatla S, Pervin A, Zhang H, Jiang S, Willardsen JA, et al. Discovery of 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (EP128265, MPI-0441138) as a potent inducer of apoptosis with high in vivo activity. J Med Chem. 2008;51:4771–9.PubMedGoogle Scholar
  27. 27.
    Tsimberidou AM, Akerley W, Schabel MC, Hong DS, Uehara C, Chhabra A, et al. Phase I clinical trial of MPC-6827 (Azixa), a microtubule destabilizing agent, in patients with advanced cancer. Mol Cancer Ther. 2010;9:3410–9.PubMedGoogle Scholar
  28. 28.
    Burns CJ, Fantino E, Phillips ID, Su S, Harte MF, Bukczynska PE, et al. CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo. Mol Cancer Ther. 2009;8:3036–45.PubMedGoogle Scholar
  29. 29.
    Shiand W, Siemann DW. Preclinical studies of the novel vascular disrupting agent MN-029. Anticancer Res. 2005;25:3899–904.Google Scholar
  30. 30.
    Ricart AD, Ashton EA, Cooney MM, Sarantopoulos J, Brell JM, Feldman MA, et al. A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors. Cancer Chemotherapy and Pharmacology. 2011;68:959–70.PubMedGoogle Scholar
  31. 31.
    de Ines C, Leynadier D, Barasoain I, Peyrot V, Garcia P, Briand C, et al. Inhibition of microtubules and cell cycle arrest by a new 1-deaza-7,8-dihydropteridine antitumor drug, CI 980, and by its chiral isomer, NSC 613863. Cancer Res. 1994;54:75–84.PubMedGoogle Scholar
  32. 32.
    Thomas JP, Moore T, Kraut EH, Balcerzak SP, Galloway S, Vandre DD. A phase II study of CI-980 in previously untreated extensive small cell lung cancer: an Ohio State University phase II research consortium study. Cancer Investigation. 2002;20:192–8.PubMedGoogle Scholar
  33. 33.
    Yoon JT, Palazzo AF, Xiao D, Delohery TM, Warburton PE, Bruce JN, et al. CP248, a derivative of exisulind, causes growth inhibition, mitotic arrest, and abnormalities in microtubule polymerization in glioma cells. Mol Cancer Ther. 2002;1:393–404.PubMedGoogle Scholar
  34. 34.
    Sun W, Stevenson JP, Gallo JM, Redlinger M, Haller D, Algazy K, et al. Phase I and pharmacokinetic trial of the proapoptotic sulindac analog CP-461 in patients with advanced cancer. Clin Cancer Res. 2002;8:3100–4.PubMedGoogle Scholar
  35. 35.
    Tripodi F, Pagliarin R, Fumagalli G, Bigi A, Fusi P, Orsini F, et al. Synthesis and biological evaluation of 1,4-Diaryl-2-azetidinones as specific anticancer agents: activation of adenosine monophosphate activated protein kinase and induction of apoptosis. J Med Chem. 2012;55:2112–24.Google Scholar
  36. 36.
    Bai R, Covell DG, Pei XF, Ewell JB, Nguyen NY, Brossi A, et al. Mapping the binding site of colchicinoids on beta -tubulin. 2-Chloroacetyl-2-demethylthiocolchicine covalently reacts predominantly with cysteine 239 and secondarily with cysteine 354. J Biol Chem. 2000;275:40443–52.PubMedGoogle Scholar
  37. 37.
    Dorleans A, Gigant B, Ravelli RB, Mailliet P, Mikol V, Knossow M. Variations in the colchicine-binding domain provide insight into the structural switch of tubulin. Proc Natl Acad Sci U S A. 2009;106:13775–9.PubMedGoogle Scholar
  38. 38.
    Barbier P, Dorleans A, Devred F, Sanz L, Allegro D, Alfonso C, et al. Stathmin and interfacial microtubule inhibitors recognize a naturally curved conformation of tubulin dimers. J Biol Chem. 2010;285:31672–81.PubMedGoogle Scholar
  39. 39.
    Nguyen TL, McGrath C, Hermone AR, Burnett JC, Zaharevitz DW, Day BW, et al. A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach. J Med Chem. 2005;48:6107–16.PubMedGoogle Scholar
  40. 40.
    Dutcher SK. The tubulin fraternity: alpha to eta. Curr Opin Cell Biol. 2001;13:49–54.PubMedGoogle Scholar
  41. 41.
    Simoni D, Romagnoli R, Baruchello R, Rondanin R, Rizzi M, Pavani MG, et al. Novel combretastatin analogues endowed with antitumor activity. J Med Chem. 2006;49:3143–52.PubMedGoogle Scholar
  42. 42.
    Stevenson JP, Rosen M, Sun W, Gallagher M, Haller DG, Vaughn D, et al. Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2003;21:4428–38.Google Scholar
  43. 43.
    Tron GC, Pirali T, Sorba G, Pagliai F, Busacca S, Genazzani AA. Medicinal chemistry of combretastatin A4: present and future directions. J Med Chem. 2006;49:3033–44.PubMedGoogle Scholar
  44. 44.
    Aprile S, Del Grosso E, Tron GC, Grosa G. In vitro metabolism study of combretastatin A-4 in rat and human liver microsomes. Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2007;35:2252–61.Google Scholar
  45. 45.
    Gwaltney 2nd SL, Imade HM, Barr KJ, Li Q, Gehrke L, Credo RB, et al. Novel sulfonate analogues of combretastatin A-4: potent antimitotic agents. Bioorganic & Medicinal Chemistry Letters. 2001;11:871–4.Google Scholar
  46. 46.
    Fortin S, Wei L, Moreau E, Lacroix J, Cote MF, Petitclerc E, et al. synthesis, biological evaluation, and structure-activity relationships of substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates as new tubulin inhibitors mimicking combretastatin A-4. J Med Chem. 2011;54:4559–80.PubMedGoogle Scholar
  47. 47.
    Fortin S, Wei L, Moreau E, Lacroix J, Cote MF, Petitclerc E, et al. Substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonamides as antimitotics. Antiproliferative, antiangiogenic and antitumoral activity, and quantitative structure-activity relationships. European Journal of Medicinal Chemistry. 2011;46:5327–42.PubMedGoogle Scholar
  48. 48.
    Simoni D, Romagnoli R, Baruchello R, Rondanin R, Grisolia G, Eleopra M, et al. Novel A-ring and B-ring modified combretastatin A-4 (CA-4) analogues endowed with interesting cytotoxic activity. J Med Chem. 2008;51:6211–5.PubMedGoogle Scholar
  49. 49.
    Ohsumi K, Hatanaka T, Fujita K, Nakagawa R, Fukuda Y, Nihei Y, et al. Syntheses and antitumor activity of cis-restricted combretastatins: 5-membered heterocyclic analogues. Bioorganic & Medicinal Chemistry Letters. 1998;8:3153–8.Google Scholar
  50. 50.
    Wang L, Woods KW, Li Q, Barr KJ, McCroskey RW, Hannick SM, et al. Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. J Med Chem. 2002;45:1697–711.PubMedGoogle Scholar
  51. 51.
    Kim Y, Nam NH, You YJ, Ahn BZ. Synthesis and cytotoxicity of 3,4-diaryl-2(5H)-furanones. Bioorganic & Medicinal Chemistry Letters. 2002;12:719–22.Google Scholar
  52. 52.
    Nam NH, Kim Y, You YJ, Hong DH, Kim HM, Ahn BZ. Synthesis and anti-tumor activity of novel combretastatins: combretocyclopentenones and related analogues. Bioorganic & Medicinal Chemistry Letters. 2002;12:1955–8.Google Scholar
  53. 53.
    Nam NH, Kim Y, You YJ, Hong DH, Kim HM, Ahn BZ. Combretoxazolones: synthesis, cytotoxicity and antitumor activity. Bioorganic & Medicinal Chemistry Letters. 2001;11:3073–6.Google Scholar
  54. 54.
    Bailly C, Bal C, Barbier P, Combes S, Finet JP, Hildebrand MP, et al. Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins. J Med Chem. 2003;46:5437–44.PubMedGoogle Scholar
  55. 55.
    Combes S, Barbier P, Douillard S, McLeer-Florin A, Bourgarel-Rey V, Pierson JT, et al. Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins. Part 2. J Med Chem. 2011;54:3153–62.PubMedGoogle Scholar
  56. 56.
    Tron GC, Pagliai F, Del Grosso E, Genazzani AA, Sorba G. Synthesis and cytotoxic evaluation of combretafurazans. J Med Chem. 2005;48:3260–8.PubMedGoogle Scholar
  57. 57.
    Pati HN, Wicks M, Holt HL, Leblanc R, Weisbruch P, Forrest L, et al. Synthesis and biological evaluation of cis-combretastatin analogs and their novel 1,2,3-triazole derivatives. Heterocyclic Commun. 2005;11:117–20.Google Scholar
  58. 58.
    Simoni D, Grisolia G, Giannini G, Roberti M, Rondanin R, Piccagli L, et al. Heterocyclic and phenyl double-bond-locked combretastatin analogues possessing potent apoptosis-inducing activity in HL60 and in MDR cell lines. J Med Chem. 2005;48:723–36.PubMedGoogle Scholar
  59. 59.
    Flynn BL, Flynn GP, Hamel E, Jung MK. The synthesis and tubulin binding activity of thiophene-based analogues of combretastatin A-4. Bioorganic & Medicinal Chemistry Letters. 2001;11:2341–3.Google Scholar
  60. 60.
    O'Boyle NM, Carr M, Greene LM, Bergin O, Nathwani SM, McCabe T, et al. Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents. J Med Chem. 2010;53:8569–84.PubMedGoogle Scholar
  61. 61.
    Romagnoli R, Baraldi PG, Brancale A, Ricci A, Hamel E, Bortolozzi R, et al. Convergent synthesis and biological evaluation of 2-amino-4-(3',4',5'-trimethoxyphenyl)-5-aryl thiazoles as microtubule targeting agents. J Med Chem. 2011;54:5144–53.PubMedGoogle Scholar
  62. 62.
    Beale TM, Allwood DM, Bender A, Bond PJ, Brenton JD, Charnock-Jones DS, et al. Xian A-ring dihalogenation increases the cellular activity of combretastatin-templated tetrazoles. ACS Medicinal Chemistry Letters: Ahead of Print, 2012.Google Scholar
  63. 63.
    Schobert R, Biersack B, Dietrich A, Effenberger K, Knauer S, Mueller T. 4-(3-Halo/amino-4,5-dimethoxyphenyl)-5-aryloxazoles and -N-methylimidazoles that are cytotoxic against combretastatin A resistant tumor cells and vascular disrupting in a cisplatin resistant germ cell tumor model. J Med Chem. 2010;53:6595–602.PubMedGoogle Scholar
  64. 64.
    Theeramunkong S, Caldarelli A, Massarotti A, Aprile S, Caprioglio D, Zaninetti R, et al. Regioselective Suzuki coupling of dihaloheteroaromatic compounds as a rapid strategy to synthesize potent rigid combretastatin analogues. J Med Chem. 2011;54:4977–86.PubMedGoogle Scholar
  65. 65.
    Furst R, Zupko I, Berenyi A, Ecker GF, Rinner U. Synthesis and antitumor-evaluation of cyclopropyl-containing combretastatin analogs. Bioorganic & Medicinal Chemistry Letters. 2009;19:6948–51.Google Scholar
  66. 66.
    Hadfield JA, Gaukroger K, Hirst N, Weston AP, Lawrence NJ, McGown AT. Synthesis and evaluation of double bond substituted combretastatins. European Journal of Medicinal Chemistry. 2005;40:529–41.PubMedGoogle Scholar
  67. 67.
    Liu T, Cui R, Chen J, Zhang J, He Q, Yang B, et al. 4,5-Diaryl-3-aminopyrazole derivatives as analogs of Combretastatin A-4: synthesis and biological evaluation. Arch Pharm. 2011;344:279–86.Google Scholar
  68. 68.
    Akselsen OW, Odlo K, Cheng JJ, Maccari G, Botta M, Hansen TV. Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs of combretastatin A-1. Bioorg Med Chem. 2012;20:234–42.PubMedGoogle Scholar
  69. 69.
    Xue N, Yang X, Wu R, Chen J, He Q, Yang B, et al. Synthesis and biological evaluation of imidazol-2-one derivatives as potential antitumor agents. Bioorg Med Chem. 2008;16:2550–7.PubMedGoogle Scholar
  70. 70.
    Ruprich J, Prout A, Dickson J, Younglove B, Nolan L, Baxi K, et al. Design, synthesis and biological testing of cyclohexenone derivatives of combretastatin-A4. Letters in Drug Design & Discovery. 2007;4:144–8.Google Scholar
  71. 71.
    Lee L, Davis R, Vanderham J, Hills P, Mackay H, Brown T, et al. 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4. European Journal of Medicinal Chemistry. 2008;43:2011–5.PubMedGoogle Scholar
  72. 72.
    Johnson M, Younglove B, Lee L, LeBlanc R, Holt Jr H, Hills P, et al. Design, synthesis, and biological testing of pyrazoline derivatives of combretastatin-A4. Bioorganic & Medicinal Chemistry Letters. 2007;17:5897–901.Google Scholar
  73. 73.
    Mateo C, Perez-Melero C, Pelaez R, Medarde M. Stilbenophane analogues of deoxycombretastatin A-4. J Org Chem. 2005;70:6544–7.PubMedGoogle Scholar
  74. 74.
    De Martino G, Edler MC, La Regina G, Coluccia A, Barbera MC, Barrow D, et al. New arylthioindoles: potent inhibitors of tubulin polymerization. 2. Structure-activity relationships and molecular modeling studies. J Med Chem. 2006;49:947–54.PubMedGoogle Scholar
  75. 75.
    De Martino G, La Regina G, Coluccia A, Edler MC, Barbera MC, Brancale A, et al. Arylthioindoles, potent inhibitors of tubulin polymerization. J Med Chem. 2004;47:6120–3.PubMedGoogle Scholar
  76. 76.
    La Regina G, Sarkar T, Bai R, Edler MC, Saletti R, Coluccia A, et al. New arylthioindoles and related bioisosteres at the sulfur bridging group. 4. Synthesis, tubulin polymerization, cell growth inhibition, and molecular modeling studies. J Med Chem. 2009;52:7512–27.PubMedGoogle Scholar
  77. 77.
    La Regina G, Bai R, Rensen W, Coluccia A, Piscitelli F, Gatti V, et al. Design and synthesis of 2-Heterocyclyl-3-arylthio-1H-indoles as potent tubulin polymerization and cell growth inhibitors with improved metabolic stability. J Med Chem. 2011;54:8394–406.PubMedGoogle Scholar
  78. 78.
    Mahboobi S, Pongratz H, Hufsky H, Hockemeyer J, Frieser M, Lyssenko A, et al. Synthetic 2-aroylindole derivatives as a new class of potent tubulin-inhibitory, antimitotic agents. J Med Chem. 2001;44:4535–53.PubMedGoogle Scholar
  79. 79.
    Kuo CC, Hsieh HP, Pan WY, Chen CP, Liou JP, Lee SJ, et al. BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res. 2004;64:4621–8.PubMedGoogle Scholar
  80. 80.
    Hu CB, Chen CP, Yeh TK, Song JS, Chang CY, Chuu JJ, et al. BPR0C261 is a novel orally active antitumor agent with antimitotic and anti-angiogenic activities. Cancer Science. 2011;102:182–91.PubMedGoogle Scholar
  81. 81.
    Li WT, Hwang DR, Chen CP, Shen CW, Huang CL, Chen TW, et al. Synthesis and biological evaluation of N-heterocyclic indolyl glyoxylamides as orally active anticancer agents. J Med Chem. 2003;46:1706–15.PubMedGoogle Scholar
  82. 82.
    Nien CY, Chen YC, Kuo CC, Hsieh HP, Chang CY, Wu JS, et al. 5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors. J Med Chem. 2010;53:2309–13.PubMedGoogle Scholar
  83. 83.
    Liou JP, Wu ZY, Kuo CC, Chang CY, Lu PY, Chen CM, et al. Discovery of 4-amino and 4-hydroxy-1-aroylindoles as potent tubulin polymerization inhibitors. J Med Chem. 2008;51:4351–5.PubMedGoogle Scholar
  84. 84.
    Lee HY, Chang JY, Nien CY, Kuo CC, Shih KH, Wu CH, et al. 5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors. Part 2. The impact of bridging groups at position C-2. J Med Chem. 2011;54:8517–25.PubMedGoogle Scholar
  85. 85.
    Arthuis M, Pontikis R, Chabot GG, Quentin L, Scherman D, Florent JC. Domino approach to 2-aroyltrimethoxyindoles as novel heterocyclic combretastatin A4 analogues. European Journal of Medicinal Chemistry. 2011;46:95–100.PubMedGoogle Scholar
  86. 86.
    Lai MJ, Chang JY, Lee HY, Kuo CC, Lin MH, Hsieh HP, et al. Synthesis and biological evaluation of 1-(4'-Indolyl and 6'-Quinolinyl) indoles as a new class of potent anticancer agents. European Journal of Medicinal Chemistry. 2011;46:3623–9.PubMedGoogle Scholar
  87. 87.
    Lai MJ, Kuo CC, Yeh TK, Hsieh HP, Chen LT, Pan WY, et al. Synthesis and structure-activity relationships of 1-benzyl-4,5,6-trimethoxyindoles as a novel class of potent antimitotic agents. ChemMedChem. 2009;4:588–93.PubMedGoogle Scholar
  88. 88.
    Xie F, Zhao H, Li D, Chen H, Quan H, Shi X, et al. Synthesis and biological evaluation of 2,4,5-substituted pyrimidines as a new class of tubulin polymerization inhibitors. J Med Chem. 2011;54:3200–5.PubMedGoogle Scholar
  89. 89.
    El-Nakkady SS, Hanna MM, Roaiah HM, Ghannam IA. Synthesis, molecular docking study and antitumor activity of novel 2-phenylindole derivatives. European Journal of Medicinal Chemistry. 2012;47:387–98.PubMedGoogle Scholar
  90. 90.
    Arora S, Wang XI, Keenan SM, Andaya C, Zhang Q, Peng Y, et al. Novel microtubule polymerization inhibitor with potent antiproliferative and antitumor activity. Cancer Res. 2009;69:1910–5.PubMedGoogle Scholar
  91. 91.
    Shetty RS, Lee Y, Liu B, Husain A, Joseph RW, Lu Y, et al. Synthesis and pharmacological evaluation of N-(3-(1H-indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a potent antimitotic agent. J Med Chem. 2011;54:179–200.PubMedGoogle Scholar
  92. 92.
    Li L, Wang HK, Kuo SC, Wu TS, Mauger A, Lin CM, et al. Antitumor agents. 155. Synthesis and biological evaluation of 3',6,7-substituted 2-phenyl-4-quinolones as antimicrotubule agents. J Med Chem. 1994;37:3400–7.PubMedGoogle Scholar
  93. 93.
    Li L, Wang HK, Kuo SC, Wu TS, Lednicer D, Lin CM, et al. Antitumor agents. 150. 2',3',4',5',5,6,7-substituted 2-phenyl-4-quinolones and related compounds: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J Med Chem. 1994;37:1126–35.PubMedGoogle Scholar
  94. 94.
    Zhang C, Yang N, Yang CH, Ding HS, Luo C, Zhang Y, et al. S9, a novel anticancer agent, exerts its anti-proliferative activity by interfering with both PI3K-Akt-mTOR signaling and microtubule cytoskeleton. PLoS One. 2009;4:e4881.PubMedGoogle Scholar
  95. 95.
    Romagnoli R, Baraldi PG, Carrion MD, Lopez Cara C, Preti D, Fruttarolo F, et al. Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization. J Med Chem. 2007;50:2273–7.PubMedGoogle Scholar
  96. 96.
    Keller L, Beaumont S, Liu JM, Thoret S, Bignon JS, Wdzieczak-Bakala J, et al. New C5-alkylated indolobenzazepinones acting as inhibitors of tubulin polymerization: cytotoxic and antitumor activities. J Med Chem. 2008;51:3414–21.PubMedGoogle Scholar
  97. 97.
    Pons V, Beaumont S, Dau METH, Iorga BI, Dodd RH. Rigid analogues of antimitotic indolobenzazepinones: new insights into tubulin binding via molecular modeling. ACS Medicinal Chemistry Letters. 2011;2:565–570.Google Scholar
  98. 98.
    Boumendjel A, McLeer-Florin A, Champelovier P, Allegro D, Muhammad D, Souard F, et al. A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models. BMC Cancer. 2009;9:242.PubMedGoogle Scholar
  99. 99.
    Kerr DJ, Hamel E, Jung MK, Flynn BL. The concise synthesis of chalcone, indanone and indenone analogues of combretastatin A4. Bioorg Med Chem. 2007;15:3290–8.PubMedGoogle Scholar
  100. 100.
    Luo Y, Qiu KM, Lu X, Liu K, Fu J, Zhu HL. Synthesis, biological evaluation, and molecular modeling of cinnamic acyl sulfonamide derivatives as novel antitubulin agents. Bioorg Med Chem. 2011;19:4730–8.PubMedGoogle Scholar
  101. 101.
    Ruan BF, Lu X, Tang JF, Wei Y, Wang XL, Zhang YB, et al. Synthesis, biological evaluation, and molecular docking studies of resveratrol derivatives possessing chalcone moiety as potential antitubulin agents. Bioorg Med Chem. 2011;19:2688–95.PubMedGoogle Scholar
  102. 102.
    Risinger AL, Westbrook CD, Encinas A, Mulbaier M, Schultes CM, Wawro S, et al. ELR510444, a novel microtubule disruptor with multiple mechanisms of action. J Pharmacol Exp Ther. 2011;336:652–60.PubMedGoogle Scholar
  103. 103.
    Chang JY, Hsieh HP, Chang CY, Hsu KS, Chiang YF, Chen CM, et al. 7-Aroyl-aminoindoline-1-sulfonamides as a novel class of potent antitubulin agents. J Med Chem. 2006;49:6656–9.PubMedGoogle Scholar
  104. 104.
    Liou JP, Hsu KS, Kuo CC, Chang CY, Chang JY. 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. J Pharmacol Exp Ther. 2007;323:398–405.PubMedGoogle Scholar
  105. 105.
    Cushman M, He HM, Katzenellenbogen JA, Varma RK, Hamel E, Lin CM, et al. Synthesis of analogs of 2-methoxyestradiol with enhanced inhibitory effects on tubulin polymerization and cancer cell growth. J Med Chem. 1997;40:2323–34.PubMedGoogle Scholar
  106. 106.
    Cushman M, Mohanakrishnan AK, Hollingshead M, Hamel E. The effect of exchanging various substituents at the 2-position of 2-methoxyestradiol on cytotoxicity in human cancer cell cultures and inhibition of tubulin polymerization. J Med Chem. 2002;45:4748–54.PubMedGoogle Scholar
  107. 107.
    Edsall AB, Mohanakrishnan AK, Yang D, Fanwick PE, Hamel E, Hanson AD, et al. Effects of altering the electronics of 2-methoxyestradiol on cell proliferation, on cytotoxicity in human cancer cell cultures, and on tubulin polymerization. J Med Chem. 2004;47:5126–39.PubMedGoogle Scholar
  108. 108.
    Agoston GE, Shah JH, Lavallee TM, Zhan X, Pribluda VS, Treston AM. Synthesis and structure-activity relationships of 16-modified analogs of 2-methoxyestradiol. Bioorg Med Chem. 2007;15:7524–37.PubMedGoogle Scholar
  109. 109.
    Chander SK, Foster PA, Leese MP, Newman SP, Potter BV, Purohit A, et al. In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol. Br J Cancer. 2007;96:1368–76.PubMedGoogle Scholar
  110. 110.
    Ireson CR, Chander SK, Purohit A, Perera S, Newman SP, Parish D, et al. Pharmacokinetics and efficacy of 2-methoxyoestradiol and 2-methoxyoestradiol-bis-sulphamate in vivo in rodents. Br J Cancer. 2004;90:932–7.PubMedGoogle Scholar
  111. 111.
    Jourdan F, Leese MP, Dohle W, Hamel E, Ferrandis E, Newman SP, et al. Synthesis, antitubulin, and antiproliferative SAR of analogues of 2-methoxyestradiol-3,17-O,O-bis-sulfamate. J Med Chem. 2010;53:2942–51.PubMedGoogle Scholar
  112. 112.
    Nakagawa-Goto K, Chen TH, Peng CY, Bastow KF, Wu JH, Lee KH. Antitumor agents 259. Design, syntheses, and structure-activity relationship study of desmosdumotin C analogs. J Med Chem. 2007;50:3354–8.PubMedGoogle Scholar
  113. 113.
    Nakagawa-Goto K, Bastow KF, Chen TH, Morris-Natschke SL, Lee KH. Antitumor agents 260. New desmosdumotin B analogues with improved in vitro anticancer activity. J Med Chem. 2008;51:3297–303.PubMedGoogle Scholar
  114. 114.
    Nakagawa-Goto K, Wu PC, Lai CY, Hamel E, Zhu H, Zhang L, et al. Antitumor agents. 284. New desmosdumotin B analogues with bicyclic B-ring as cytotoxic and antitubulin agents. J Med Chem. 2011;54:1244–55.PubMedGoogle Scholar
  115. 115.
    Nakagawa-Goto K, Wu PC, Bastow KF, Yang SC, Yu SL, Chen HY, et al. Antitumor agents 283. Further elaboration of desmosdumotin C analogs as potent antitumor agents: activation of spindle assembly checkpoint as possible mode of action. Bioorg Med Chem. 2011;19:1816–22.PubMedGoogle Scholar
  116. 116.
    Beutler JA, Cardellina JH II, Lin CM, Hamel E, Cragg GM, Boyd MR. Centaureidin, a cytotoxic flavone from Polymnia fruticosa, inhibits tubulin polymerization. Bioorganic & Medicinal Chemistry Letters. 1993;3:581–4.Google Scholar
  117. 117.
    Naik PK, Chatterji BP, Vangapandu SN, Aneja R, Chandra R, Kanteveri S, et al. Rational design, synthesis and biological evaluations of amino-noscapine: a high affinity tubulin-binding noscapinoid. J Comput Aided Mol Des. 2011;25:443–54.PubMedGoogle Scholar
  118. 118.
    Hartley RM, Peng J, Fest GA, Dakshanamurthy S, Frantz DE, Brown ML, et al. Polygamain, a new microtubule depolymerizing agent that occupies a unique pharmacophore in the colchicine site. Molecular Pharmacology. 2011.Google Scholar
  119. 119.
    Cui CB, Kakeya H, Okada G, Onose R, Ubukata M, Takahashi I, et al. Tryprostatins A and B, novel mammalian cell cycle inhibitors produced by Aspergillus fumigatus. J Antibiot. 1995;48:1382–4.PubMedGoogle Scholar
  120. 120.
    Woehlecke H, Osada H, Herrmann A, Lage H. Reversal of breast cancer resistance protein-mediated drug resistance by tryprostatin A. International Journal of Cancer Journal International Du Cancer. 2003;107:721–8.PubMedGoogle Scholar
  121. 121.
    Kanoh K, Kohno S, Katada J, Takahashi J, Uno I. (-)-Phenylahistin arrests cells in mitosis by inhibiting tubulin polymerization. J Antibiot. 1999;52:134–41.PubMedGoogle Scholar
  122. 122.
    Kanzaki H, Yanagisawa S, Kanoh K, Nitoda T. A novel potent cell cycle inhibitor dehydrophenylahistin–enzymatic synthesis and inhibitory activity toward sea urchin embryo. J Antibiot. 2002;55:1042–7.PubMedGoogle Scholar
  123. 123.
    Yamazaki Y, Tanaka K, Nicholson B, Deyanat-Yazdi G, Potts B, Yoshida T, et al. Synthesis and Structure-Activity Relationship Study of Antimicrotubule Agents Phenylahistin Derivatives with a Didehydropiperazine-2,5-dione Structure. J Med Chem. 2012;55:1056–71.PubMedGoogle Scholar
  124. 124.
    Wipf P, Reeves JT, Balachandran R, Day BW. Synthesis and biological evaluation of structurally highly modified analogues of the antimitotic natural product curacin A. J Med Chem. 2002;45:1901–17.PubMedGoogle Scholar
  125. 125.
    Wipf P, Reeves JT, Balachandran R, Giuliano KA, Hamel E, Day BW. Synthesis and Biological Evaluation of a Focused Mixture Library of Analogues of the Antimitotic Marine Natural Product Curacin A. J Am Chem Soc. 2000;122:9391–5.Google Scholar
  126. 126.
    Ziegelbauer J, Shan B, Yager D, Larabell C, Hoffmann B, Tjian R. Transcription factor MIZ-1 is regulated via microtubule association. Molecular Cell. 2001;8:339–49.PubMedGoogle Scholar
  127. 127.
    Bai R, Pei XF, Boye O, Getahun Z, Grover S, Bekisz J, et al. Identification of cysteine 354 of beta-tubulin as part of the binding site for the A ring of colchicine. J Biol Chem. 1996;271:12639–45.PubMedGoogle Scholar
  128. 128.
    Combeau C, Provost J, Lancelin F, Tournoux Y, Prod'homme F, Herman F, et al. RPR112378 and RPR115781: two representatives of a new family of microtubule assembly inhibitors. Mol Pharmacol. 2000;57:553–63.PubMedGoogle Scholar
  129. 129.
    Bouchon B, Chambon C, Mounetou E, Papon J, Miot-Noirault E, Gaudreault RC, et al. Alkylation of beta-tubulin on Glu 198 by a microtubule disrupter. Mol Pharmacol. 2005;68:1415–22.PubMedGoogle Scholar
  130. 130.
    Fortin S, Bouchon B, Chambon C, Lacroix J, Moreau E, Chezal JM, et al. Characterization of the covalent binding of N-phenyl-N'-(2-chloroethyl)ureas to {beta}-tubulin: importance of Glu198 in microtubule stability. J Pharmacol Exp Ther. 2011;336:460–7.PubMedGoogle Scholar
  131. 131.
    Prinz H, Schmidt P, Bohm KJ, Baasner S, Muller K, Gerlach M, et al. Phenylimino-10H-anthracen-9-ones as novel antimicrotubule agents-synthesis, antiproliferative activity and inhibition of tubulin polymerization. Bioorg Med Chem. 2011;19:4183–91.PubMedGoogle Scholar
  132. 132.
    Kasibhatla S, Gourdeau H, Meerovitch K, Drewe J, Reddy S, Qiu L, et al. Discovery and mechanism of action of a novel series of apoptosis inducers with potential vascular targeting activity. Mol Cancer Ther. 2004;3:1365–74.PubMedGoogle Scholar
  133. 133.
    Kemnitzer W, Drewe J, Jiang S, Zhang H, Crogan-Grundy C, Labreque D, et al. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. 4. Structure-activity relationships of N-alkyl substituted pyrrole fused at the 7,8-positions. J Med Chem. 2008;51:417–23.PubMedGoogle Scholar
  134. 134.
    Henderson MC, Shaw YJ, Wang H, Han H, Hurley LH, Flynn G, et al. UA62784, a novel inhibitor of centromere protein E kinesin-like protein. Mol Cancer Ther. 2009;8:36–44.PubMedGoogle Scholar
  135. 135.
    Tcherniuk S, Deshayes S, Sarli V, Divita G, Abrieu A. UA62784 Is a cytotoxic inhibitor of microtubules, not CENP-E. Chem Biol. 2011;18:631–41.PubMedGoogle Scholar
  136. 136.
    Dalyot-Herman N, Delgado-Lopez F, Gewirtz DA, Gupton JT, Schwartz EL. Interference with endothelial cell function by JG-03-14, an agent that binds to the colchicine site on microtubules. Biochem Pharmacol. 2009;78:1167–77.PubMedGoogle Scholar
  137. 137.
    Mooberry SL, Weiderhold KN, Dakshanamurthy S, Hamel E, Banner EJ, Kharlamova A, et al. Identification and characterization of a new tubulin-binding tetrasubstituted brominated pyrrole. Mol Pharmacol. 2007;72:132–40.PubMedGoogle Scholar
  138. 138.
    Zhang Z, Meng T, Yang N, Wang W, Xiong B, Chen Y, et al. MT119, a new planar-structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation. International Journal of Cancer Journal International Du Cancer. 2011;129:214–24.PubMedGoogle Scholar
  139. 139.
    Lisowski V, Leonce S, Kraus-Berthier L, Sopkova-de Oliveira Santos J, Pierre A, Atassi G, et al. Design, synthesis, and evaluation of novel thienopyrrolizinones as antitubulin agents. J Med Chem. 2004;47:1448–64.PubMedGoogle Scholar
  140. 140.
    Leoni LM, Hamel E, Genini D, Shih H, Carrera CJ, Cottam HB, et al. Indanocine, a microtubule-binding indanone and a selective inducer of apoptosis in multidrug-resistant cancer cells. J Natl Cancer Inst. 2000;92:217–24.PubMedGoogle Scholar
  141. 141.
    Liberatore AM, Coulomb H, Pons D, Dutruel O, Kasprzyk PG, Carlson M, et al. IRC-083927 is a new tubulin binder that inhibits growth of human tumor cells resistant to standard tubulin-binding agents. Mol Cancer Ther. 2008;7:2426–34.PubMedGoogle Scholar
  142. 142.
    Wasylyk C, Zheng H, Castell C, Debussche L, Multon MC, Wasylyk B. Inhibition of the Ras-Net (Elk-3) pathway by a novel pyrazole that affects microtubules. Cancer Res. 2008;68:1275–83.PubMedGoogle Scholar
  143. 143.
    Shin KD, Yoon YJ, Kang YR, Son KH, Kim HM, Kwon BM, et al. KRIBB3, a novel microtubule inhibitor, induces mitotic arrest and apoptosis in human cancer cells. Biochem Pharmacol. 2008;75:383–94.PubMedGoogle Scholar
  144. 144.
    Szczepankiewicz BG, Liu G, Jae HS, Tasker AS, Gunawardana IW, von Geldern TW, et al. New antimitotic agents with activity in multi-drug-resistant cell lines and in vivo efficacy in murine tumor models. J Med Chem. 2001;44:4416–30.PubMedGoogle Scholar
  145. 145.
    Tahir SK, Han EK, Credo B, Jae HS, Pietenpol JA, Scatena CD, et al. A-204197, a new tubulin-binding agent with antimitotic activity in tumor cell lines resistant to known microtubule inhibitors. Cancer Res. 2001;61:5480–5.PubMedGoogle Scholar
  146. 146.
    Li Q, Woods KW, Claiborne A, Gwaltney 2nd SL, Barr KJ, Liu G, et al. Synthesis and biological evaluation of 2-indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent. Bioorganic & Medicinal Chemistry Letters. 2002;12:465–9.Google Scholar
  147. 147.
    Tahir SK, Nukkala MA, Zielinski Mozny NA, Credo RB, Warner RB, Li Q, et al. Biological activity of A-289099: an orally active tubulin-binding indolyloxazoline derivative. Mol Cancer Ther. 2003;2:227–33.PubMedGoogle Scholar
  148. 148.
    Andreani A, Burnelli S, Granaiola M, Leoni A, Locatelli A, Morigi R, et al. Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones: selectivity against colon tumor cells and effect on cell cycle-related events. J Med Chem. 2008;51:7508–13.PubMedGoogle Scholar
  149. 149.
    Andreani A, Granaiola M, Locatelli A, Morigi R, Rambaldi M, Varoli L, et al. Substituted 3-(5-Imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues: synthesis, cytotoxic activity, and study of the mechanism of action (1). J Med Chem. 2012.Google Scholar
  150. 150.
    Edsall AB, Agoston GE, Treston AM, Plum SM, McClanahan RH, Lu TS, et al. Synthesis and in vivo antitumor evaluation of 2-methoxyestradiol 3-phosphate, 17-phosphate, and 3,17-diphosphate. J Med Chem. 2007;50:6700–5.PubMedGoogle Scholar
  151. 151.
    Rubenstein SM, Baichwal V, Beckmann H, Clark DL, Frankmoelle W, Roche D, et al. Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier. J Med Chem. 2001;44:3599–605.PubMedGoogle Scholar
  152. 152.
    Crielaard BJ, van der Wal S, Lammers T, Le HT, Hennink WE, Schiffelers RM, et al. A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy. International Journal of Nanomedicine. 2011;6:2697–703.PubMedGoogle Scholar
  153. 153.
    Crielaard BJ, van der Wal S, Le HT, Bode AT, Lammers T, Hennink WE, et al. Liposomes as carriers for colchicine-derived prodrugs: Vascular disrupting nanomedicines with tailorable drug release kinetics. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences. 2012;45:429–35.Google Scholar
  154. 154.
    Lu Y, Li CM, Wang Z, Ross 2nd CR, Chen J, Dalton JT, et al. Discovery of 4-substituted methoxybenzoyl-aryl-thiazole as novel anticancer agents: synthesis, biological evaluation, and structure-activity relationships. J Med Chem. 2009;52:1701–11.PubMedGoogle Scholar
  155. 155.
    Li CM, Wang Z, Lu Y, Ahn S, Narayanan R, Kearbey JD, et al. Biological activity of 4-substituted methoxybenzoyl-aryl-thiazole: an active microtubule inhibitor. Cancer Res. 2011;71:216–24.PubMedGoogle Scholar
  156. 156.
    Li F, Lu Y, Li W, Miller DD, Mahato RI. Synthesis, formulation and in vitro evaluation of a novel microtubule destabilizer, SMART-100. Journal of Controlled Release: Official Journal of the Controlled Release Society. 2010;143:151–8.Google Scholar
  157. 157.
    Chen J, Wang Z, Li CM, Lu Y, Vaddady PK, Meibohm B, et al. Discovery of novel 2-aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents. J Med Chem. 2010;53:7414–27.PubMedGoogle Scholar
  158. 158.
    Babu B, Lee M, Lee L, Strobel R, Brockway O, Nickols A, et al. Acetyl analogs of combretastatin A-4: synthesis and biological studies. Bioorg Med Chem. 2011;19:2359–67.PubMedGoogle Scholar
  159. 159.
    Lee M, Brockway O, Dandavati A, Tzou S, Sjoholm R, Satam V, et al. A novel class of trans-methylpyrazoline analogs of combretastatins: synthesis and in-vitro biological testing. European Journal of Medicinal Chemistry. 2011;46:3099–104.PubMedGoogle Scholar
  160. 160.
    Gangjee A, Zhao Y, Hamel E, Westbrook C, Mooberry SL. Synthesis and biological activities of (R)- and (S)-N-(4-Methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimi din-4-aminium chloride as potent cytotoxic antitubulin agents. J Med Chem. 2011;54:6151–5.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Yan Lu
    • 1
  • Jianjun Chen
    • 1
  • Min Xiao
    • 1
  • Wei Li
    • 1
  • Duane D. Miller
    • 1
    Email author
  1. 1.Department of Pharmaceutical Sciences, Health Science CenterUniversity of TennesseeMemphisUSA

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