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Cellular and Molecular Biology Letters

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Volume 18, Issue 3


Tubulin-interactive stilbene derivatives as anticancer agents

Renata Mikstacka / Tomasz Stefański / Jakub Różański
Published Online: 2013-07-27 | DOI: https://doi.org/10.2478/s11658-013-0094-z


Microtubules are dynamic polymers that occur in eukaryotic cells and play important roles in cell division, motility, transport and signaling. They form during the process of polymerization of α- and β-tubulin dimers. Tubulin is a significant and heavily researched molecular target for anticancer drugs. Combretastatins are natural cis-stilbenes that exhibit cytotoxic properties in cultured cancer cells in vitro. Combretastatin A-4 (3′-hydroxy-3,4,4′, 5-tetramethoxy-cis-stilbene; CA-4) is a potent cytotoxic cis-stilbene that binds to β-tubulin at the colchicine-binding site and inhibits tubulin polymerization. The prodrug CA-4 phosphate is currently in clinical trials as a chemotherapeutic agent for cancer treatment. Numerous series of stilbene analogs have been studied in search of potent cytotoxic agents with the requisite tubulin-interactive properties. Microtubule-interfering agents include numerous CA-4 and transresveratrol analogs and other synthetic stilbene derivatives. Importantly, these agents are active in both tumor cells and immature endothelial cells of tumor blood vessels, where they inhibit the process of angiogenesis. Recently, computer-aided virtual screening was used to select potent tubulin-interactive compounds. This review covers the role of stilbene derivatives as a class of antitumor agents that act by targeting microtubule assembly dynamics. Additionally, we present the results of molecular modeling of their binding to specific sites on the α- and β-tubulin heterodimer. This has enabled the elucidation of the mechanism of stilbene cytotoxicity and is useful in the design of novel agents with improved anti-mitotic activity. Tubulin-interactive agents are believed to have the potential to play a significant role in the fight against cancer.

Keywords: Tubulin polymerization; Tubulin-interactive agents; Stilbenes; Combretastatins

  • [1] Butler, M.S. Natural products to drugs: natural product-derived compounds in clinical trials. Nat. Prod. Rep. 25 (2008) 475–516. http://dx.doi.org/10.1039/b514294fCrossrefGoogle Scholar

  • [2] Pettit, G.R., Cragg, G.M., Herald, D.L., Schmidt, J.M. and Lobavanijaya, P. Antineoplastic agents. Part 84. Isolation and structure of combretastatin. Can. J. Chem. 60 (1982) 1374–1376. http://dx.doi.org/10.1139/v82-202CrossrefGoogle Scholar

  • [3] Tron, G.C., Pirali, T., Sorba, G., Pagliai, F., Busacca, S. and Genazzani, A. Medicinal chemistry of combretastatin A-4: present and future directions. J. Med. Chem. 49 (2006) 3033–3044. http://dx.doi.org/10.1021/jm0512903CrossrefGoogle Scholar

  • [4] Siemann, D.W., Chaplin, D.J. and Walicke, P.A. A review and update of the current status of the vasculature-disabling agent combretastatin-A4 phosphate (CA4P). Exp. Opin. Invest. Drugs 18 (2009) 189–197. http://dx.doi.org/10.1517/13543780802691068Google Scholar

  • [5] Desai, A. and Mitchison, T.J. Microtubule polymerization dynamics. Ann. Rev. Cell Dev. Biol. 13 (1997) 83–117. http://dx.doi.org/10.1146/annurev.cellbio.13.1.83CrossrefGoogle Scholar

  • [6] Nogales, E., Wolf, S.G., and Downing, K.H. Structure of the αβ-tubulin dimer by electron crystallography. Nature 391 (1998) 199–203. http://dx.doi.org/10.1038/34465CrossrefGoogle Scholar

  • [7] Mitchison, T. and Kirscher, M. Microtubule assembly nucleated by isolated centrosomes. Nature 312 (1984) 232–237. http://dx.doi.org/10.1038/312232a0CrossrefGoogle Scholar

  • [8] Wang, H.W. and Nogales, E. Nucleotide-dependent bending flexibility of tubulin regulates microtubule assembly. Nature 435 (2005) 911–915. http://dx.doi.org/10.1038/nature03606CrossrefGoogle Scholar

  • [9] Akhmanova, A., and Steinmetz, M.O. Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat. Rev. Mol. Cell Biol. 9 (2008) 309–322. http://dx.doi.org/10.1038/nrm2369CrossrefGoogle Scholar

  • [10] Kline-Smith, S.L. and Walczak, C.E. Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics. Mol. Cell 15 (2004) 317–327. http://dx.doi.org/10.1016/j.molcel.2004.07.012CrossrefGoogle Scholar

  • [11] Kwon, M. and Scholey, J.M. Spindle mechanics and dynamics during mitosis in Drosophila. Trends Cell Biol. 14 (2004) 194–205. http://dx.doi.org/10.1016/j.tcb.2004.03.003CrossrefGoogle Scholar

  • [12] Rieder, C.L., Davison, E.A., Jensen, L.C., Cassimeris, L. and Salomon, E.D. Oscillatory movements of monooriented chromosomes and their position relative to the spindle pole result from the ejection properties of the aster and half-spindle. J. Cell Biol. 103 (1986) 581–591. http://dx.doi.org/10.1083/jcb.103.2.581CrossrefGoogle Scholar

  • [13] Higuchi, T. and Uhlmann, F. Stabilization of microtubule dynamics at anaphase onset promotes chromosome segregation. Nature 433 (2005) 171–176. http://dx.doi.org/10.1038/nature03240CrossrefGoogle Scholar

  • [14] Rieder, C.L., Schultz, A., Cole, R. and Sluder, G. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. J. Cell Biol. 127 (1994) 1301–1310. http://dx.doi.org/10.1083/jcb.127.5.1301CrossrefGoogle Scholar

  • [15] Jordan, M.A. and Wilson, L. Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 4 (2004) 253–265. http://dx.doi.org/10.1038/nrc1317CrossrefGoogle Scholar

  • [16] Singh, P., Rathinasamy, K., Mohan, R. and Panda, D. Microtubule assembly dynamics: an attractive target for anticancer drugs. IUBMB Life 60 (2008) 368–375. http://dx.doi.org/10.1002/iub.42CrossrefGoogle Scholar

  • [17] Bhattacharyya, B., Panda, D., Gupta, S., and Banerjee, M. Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med. Res. Rev. 28 (2008) 155–183. http://dx.doi.org/10.1002/med.20097CrossrefGoogle Scholar

  • [18] Ravelli, R.B., Gigant, B., Curmi P.A., Jourdain, I., Lachkar, S., Sobel, A. and Knossow, M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428 (2004) 198–202. http://dx.doi.org/10.1038/nature02393CrossrefGoogle Scholar

  • [19] Gigant, B., Wang, C., Ravelli, R.B.G., Roussi, F., Steinmetz, M.O., Curmi, P.A., Sobel, A. and Knossow, M. Structural basis for the regulation of tubulin by vinblastine. Nature 435 (2005) 519–522. http://dx.doi.org/10.1038/nature03566CrossrefGoogle Scholar

  • [20] Chakraborti, S., Das, L., Kapoor, N., Das, A., Dwivedi, V., Poddar, A., Chakraborti, G., Janik, M., Basu, G., Panda, D., Chakrabarti, P., Surolia, A. and Bhattacharyya, B. Curcumin recognizes a unique binding site of tubulin. J. Med. Chem. 54 (2011) 6183–6196. http://dx.doi.org/10.1021/jm2004046CrossrefGoogle Scholar

  • [21] Kingston, D.G.I. Tubulin-interactive natural products as anticancer agents. J. Nat. Prod. 72 (2009) 507–515. http://dx.doi.org/10.1021/np800568jCrossrefGoogle Scholar

  • [22] Nogales, E., Wolf, S.G., Khan, I.A., Luduena, R.F. and Downing, K.H. Structure of tubulin at 6.5 Å and location of the taxol-binding site. Nature 375 (1995) 424–427. http://dx.doi.org/10.1038/375424a0CrossrefGoogle Scholar

  • [23] Li, H., Wu, W.K.K., Zheng, A., Che, C.T., Yu, L., Li, Z.J., Wu, Y.C., Cheng, K.-W., Yu, J., Cho, C.H. and Wang, M. 2,3′,4,4′,5′-Pentamethoxytrans-stilbene, a resveratrol derivative, is a potent inducer of apoptosis in colon cancer cells via targeting microtubules. Biochem. Pharmacol. 78 (2009) 1224–1232. http://dx.doi.org/10.1016/j.bcp.2009.06.109CrossrefGoogle Scholar

  • [24] Goncalves, A., Braguer, D., Carles, G., Andre, N., Prevot, C. and Briand, C. Caspase-8 activation independent of CD95/CD95-L interaction during paclitaxel-induced apoptosis in human colon cancer (HT29-D4). Biochem. Pharmacol. 60 (2000) 1579–1584. http://dx.doi.org/10.1016/S0006-2952(00)00481-0CrossrefGoogle Scholar

  • [25] Siemann, D.W., Bibby, M.C., Dark, G.G., Dicker, A.P., Eskens, F.A., Horsman, M.R., Marmé, D. and LoRusso, P.M. Differentiation and definition of vascular-targeted therapies. Clin. Cancer Res. 11 (2005) 416–420. Google Scholar

  • [26] Mason, R.P., Zhao, D., Liu, L., Trawick, M.L. and Pinney, K.G. A perspective on vascular disrupting agents that interact with tubulin: preclinical tumor imaging and biological assessment. Integr. Biol (Camb.) 3 (2011) 375–387. http://dx.doi.org/10.1039/c0ib00135jCrossrefGoogle Scholar

  • [27] Siemann, D.W. The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by tumor-vascular disrupting agents. Cancer Treat. Rev. 37 (2011) 63–74. http://dx.doi.org/10.1016/j.ctrv.2010.05.001CrossrefGoogle Scholar

  • [28] Jockowich, M.E., Suarez, F., Alegret, A., Pina, Y., Hayden, B., Cebulla, C., Feuer, W. and Murray, T.G. Mechanism of retinoblastoma tumor cell death after focal chemotherapy, radiation, and vascular targeting therapy in a mouse model. Invest. Ophthalmol. Vis. Sci. 48 (2007) 5371–5376. http://dx.doi.org/10.1167/iovs.07-0708CrossrefGoogle Scholar

  • [29] Nambu, H., Nambu, R., Melia, M. and Campochiaro, P.A. Combretastatin A-4 phosphate supresses development and induces regression of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 44 (2003) 3650–3655. http://dx.doi.org/10.1167/iovs.02-0985CrossrefGoogle Scholar

  • [30] Ma, L., Liu, Y.L., Ma, Z.Z., Dou, H.L., Xu, J.H., Wang, J.C., Zhang, X. and Zhang, Q. Targeted treatment of choroidal neovascularization using integrinmediated sterically stabilized liposomes loaded with combretastatin A4. J. Ocul. Pharmacol. Ther. 25 (2009) 195–200. http://dx.doi.org/10.1089/jop.2008.0119CrossrefGoogle Scholar

  • [31] Pettit, G.R. and Singh, S., Antineoplastic agents. Part 130. Isolation, structure and synthesis of combretastatins A-2, A-3, and B-2. Can. J. Chem. 65 (1987) 2390–2396. http://dx.doi.org/10.1139/v87-399Google Scholar

  • [32] Pettit, G.R., Singh, S.B., Niven, M.L., Hamel, E. and Schmidt, J.M. Antineoplastic agents. Part 123. Isolation, structure, and synthesis of combretastatin A-1 and B-1, potent new inhibitors of microtubule assembly, derived from Combretum caffrum. J. Nat. Prod. 50 (1987) 119–131. http://dx.doi.org/10.1021/np50049a016CrossrefGoogle Scholar

  • [33] Pettit, G.R., Singh, S.B., Niven, M.L., Hamel, E., Lin, C.M., Alberts, D.S. and Garcia-Kendall, D. Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia 45 (1989) 209–211. http://dx.doi.org/10.1007/BF01954881CrossrefGoogle Scholar

  • [34] Pinney, K.G., Pettit, G.R., Trawick, M.L., Jelinek, C. and Chaplin, D.J. The discovery and development of the combretastatins. in: Anticancer Agents from Natural Products, (Cragg, G.R., Kingston, D.G.I. and Newman, D.J. Eds.) 2nd edition, CRC Press/Taylor & Francis, Boca Raton, FL, 2012, 27–63. Google Scholar

  • [35] Chaudhary, A., Pandeya, S.N., Kumar, P., Sharma, P., Gupta, S., Soni, N., Verma, K.K. and Bhardwaj, G. Combretastatin A-4 Analogs as Anticancer Agents. Mini-Rev. Med. Chem. 7 (2007) 1186–1205. http://dx.doi.org/10.2174/138955707782795647CrossrefGoogle Scholar

  • [36] Tozer, G.M., Kanthou, C., Parkins, C.S. and Hill, S.A. The biology of the combretastatins as tumour vascular targeting agents. Int. J. Exp. Pathol. 83 (2001) 21–38. http://dx.doi.org/10.1046/j.1365-2613.2002.00211.xCrossrefGoogle Scholar

  • [37] Thorpe, E.P. Vascular targeting agents as cancer therapeutics. Clin. Cancer Res. 10 (2004) 415–427. http://dx.doi.org/10.1158/1078-0432.CCR-0642-03CrossrefGoogle Scholar

  • [38] Xia, Y., Yang, A.-Y., Xia, P., Bastow, K.F., Tachibana, Y., Kuo, S.-C., Hamel, E., Hacki, T. and Lee, K.-H. J. Antitumor agents. 181. Synthesis and biological evaluation of 6,7,2′,3′,4′-substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolones as a new class of anti-mitotic antitumor agents. Med. Chem. 41 (1998) 1155–1162. http://dx.doi.org/10.1021/jm9707479CrossrefGoogle Scholar

  • [39] Wu, M., Sun, Q., Yang, C., Chen, D., Ding, J., Chen, Y., Lin, L. and Xie, Y. Synthesis and activity of combretastatin A-4 analogues: 1,2,3-thiadiazoles as potent antitumor agents. Bioorg. Med. Chem. Lett. 17 (2007) 869–873. http://dx.doi.org/10.1016/j.bmcl.2006.11.060CrossrefGoogle Scholar

  • [40] Sriram, M., Hall, J.J., Grohmann, N.C., Strecker, T.E., Wootton, T., Franken, A., Trawick, M.L. and Pinney, K.G. Design, synthesis and biological evaluation of dihydronaphthalene and benzosuberene analogs of the combretastatins as inhibitiors of tubulin polymerization in cancer chemotherapy. Bioorg. Med. Chem. 16 (2008) 8161–8171. http://dx.doi.org/10.1016/j.bmc.2008.07.050CrossrefGoogle Scholar

  • [41] Pettit, G.R., Toki, B.E., Herald, D.L., Boyd, M.R., Hamel, E., Pettit, R.K. and Chapuis, J.-C. J. Antineoplastic agents. 410. Asymetric hydroxylation of trans-combretastatin A-4. Med. Chem. 42 (1999) 1459–1465. http://dx.doi.org/10.1021/jm9807149CrossrefGoogle Scholar

  • [42] Cai, S.X. Small molecule vascular disrupting agents: potential new drugs for cancer treatment. Recent Pat. Anticancer Drug Discov. 2 (2007) 79–101. http://dx.doi.org/10.2174/157489207779561462CrossrefGoogle Scholar

  • [43] Salmon, H.W. and Siemann, D.W. Effect of the second generation vascular disrupting agent OXi4503 on tumor vascularity. Clin. Cancer Res. 12 (2006) 4090–4094. http://dx.doi.org/10.1158/1078-0432.CCR-06-0163CrossrefGoogle Scholar

  • [44] Thomson, P., Naylor, M.A., Everett, S.A., Stratford, H.R.L., Lewis, G., Hill, S., Patel, K.B., Wardman, P. and Davis, P.D. Synthesis and biological properties of bioreductively targeted nitrothienyl prodrugs of combretastatin A-4. Mol. Cancer Ther. 5 (2006) 2886–2894. http://dx.doi.org/10.1158/1535-7163.MCT-06-0429CrossrefGoogle Scholar

  • [45] Calligaris, D., Verdier-Pinard, P., Devred, F., Villard, C., Braguer, D. and Lafitte, D. Microtubule targeting agents: from biophysics to proteomics. Cell. Mol. Life Sci. 67 (2010) 1089–1104. http://dx.doi.org/10.1007/s00018-009-0245-6CrossrefGoogle Scholar

  • [46] Griggs, J., Skepper, J.N., Smith, G.A., Brindle, K.M., Metcalfe, J.C. and Hesketh, R. Inhibition of proliferative retinopathy by the antivascular agent combretastatin A-4. Am. J. Pathol. 160 (2002) 1097–1103. http://dx.doi.org/10.1016/S0002-9440(10)64930-9CrossrefGoogle Scholar

  • [47] Delmonte, A. and Sessa, C. AVE8062: A new combretastatin derivative vascular disrupting agent. Expert Opin. Investig. Drugs 18 (2009) 1541–1548. http://dx.doi.org/10.1517/13543780903213697CrossrefGoogle Scholar

  • [48] Kim, T.J., Ravoori, M., Landen, C.N., Kamatt, A.A., Han, L.Y., Lu, C., Lin, Y.G., Merritt, W.M., Jennings, N., Spannuth, W.A., Langley, R., Gershenson, D.M., Coleman, R.L., Kundra, V. and Sood, A.K. Antitumor and antivascular effects of AVE8062 in ovarian carcinoma. Cancer Res. 67 (2007) 9337–9345. http://dx.doi.org/10.1158/0008-5472.CAN-06-4018CrossrefGoogle Scholar

  • [49] Pettit, G.R., Rosenberg, H.J., Dixon, R., Knight, J.C., Hamel, E., Chapuis, J.C., Pettit, R.K., Hogan, F., Sumner, B., Ain, K.B. and Trickey-Platt, B. Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs. J. Nat. Prod. 75 (2012) 385–393. http://dx.doi.org/10.1021/np200797xCrossrefGoogle Scholar

  • [50] Baur, J.A. and Sinclair, D.A. Therapeutic potential of resveratrol: the in vivo evidence. Nat. Rev. Drug Discov. 5 (2006) 493–506. http://dx.doi.org/10.1038/nrd2060CrossrefGoogle Scholar

  • [51] Szekeres, T., Fritzer-Szekeres, M., Saiko, P. and Jaeger, W. Resveratrol and resveratrol analogues — structure-activity relationship. Pharm. Res. 27 (2010) 1042–1048. http://dx.doi.org/10.1007/s11095-010-0090-1CrossrefGoogle Scholar

  • [52] Schneider, Y., Chabert, P., Stutzmann, J., Coelho, D., Fougerousse, A., Gosse, F. Launay, J.-F., Brouillard, R. and Raul, F. Resveratrol analog (Z)-3,5,4′-trimethoxystilbene is a potent anti-mitotic drug inhibiting tubulin polymerization. Int. J. Cancer 107 (2003) 189–196. http://dx.doi.org/10.1002/ijc.11344CrossrefGoogle Scholar

  • [53] Mazué, F., Colin, D., Gobbo, J., Wegner, M., Rescifina, A., Spatafora, C., Fasseur, D., Delmas, D., Meunier, P., Triangli, C. and Latruffe, N. Structural determinants of resveratrol for cell proliferation inhibition potency. Experimental and docking studies of new analogs. Eur. J. Med. Chem. 45 (2010) 2972–2980. http://dx.doi.org/10.1016/j.ejmech.2010.03.024CrossrefGoogle Scholar

  • [54] Sale, S., Verschoyle, R.D., Boockock, D., Jones, D.J.N., Wilsher, N., Potter, G.A., Farmer, P.B., Steward, W.P. and Gescher, A.J. Pharmacokinetics in mice and growth-inhibitory properties of the putative cancer chemopreventive agent resveratrol and the synthetic analogue trans-3,4,5,4′-tetramethoxystilbene. Br. J. Cancer 90 (2004) 736–744. http://dx.doi.org/10.1038/sj.bjc.6601568CrossrefGoogle Scholar

  • [55] Sale, S., Tunstall, R.G., Ruparelia, K.C., Potter, G.A., Steward, W.P. and Gescher, A.J. Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans-3,4,5,4′-tetramethoxystilbene (DMU-212) on adenoma development in the ApcMin+ mouse and cyclooxygenase-2 in human-derived colon cancer cells. Int. J. Cancer 115 (2005) 194–201. http://dx.doi.org/10.1002/ijc.20884CrossrefGoogle Scholar

  • [56] Ma, Z., Molavi, O., Haddadi, A., Lai, R., Gossage, R.A. and Lavasanifar, A. Resveratrol analog trans 3,4,5,4′-tetramethoxystilbene (DMU-212) mediates antitumor effects via mechanism different from that of resveratrol. Cancer Chemother. Pharmacol. 63 (2008) 27–35. http://dx.doi.org/10.1007/s00280-008-0704-zCrossrefGoogle Scholar

  • [57] Park, H., Aiyar, S.E., Fan, P., Wang, J., Yue, W., Okouneva, T., Cox, C., Jordan, M.A., Demers, L., Cho, H., Kim, S., Song, R.X.-D. and Santen, R.J. Effects of tetramethoxystilbene on hormone-resistant breast cancer cells: biological and biochemical mechanisms of action. Cancer Res. 67 (2007) 5717–5726. http://dx.doi.org/10.1158/0008-5472.CAN-07-0056CrossrefGoogle Scholar

  • [58] Li, H., Wu, W.K.K., Li, Z.J., Chan, K.M., Wong, C.C.M., Ye, C.G., Yu, L., Sung, J.J.Y., Cho, C.H. and Wang, M. 2,3′,4,4′,5′-Pentamethoxy-transstilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in mice. Br. J. Pharmacol. 160 (2010) 1352–1361. http://dx.doi.org/10.1111/j.1476-5381.2010.00785.xCrossrefGoogle Scholar

  • [59] Hsieh, H.P., Liou, J.P. and Mahindroo, N. Pharmaceutical design of antimitotic agents on combretastatins. Curr. Pharm. Des. 11 (2005) 1655–1677. http://dx.doi.org/10.2174/1381612053764751CrossrefGoogle Scholar

  • [60] Hall, J.J., Sriram, M., Strecker, T.E., Tidmore, J.K., Jelinek, C.J., Kumar, G.D.K., Hadimani, M.B., Pettit, G.R., Chaplin, D.J., Trawick, M.L. and Pinney, K.G. Design, synthesis, biochemical, and biological evaluation of nitrogencontaining trifluoro structural modifications of combretastatin A-4. Bioorg. Med. Chem. Lett. 18 (2008) 5146–5149. http://dx.doi.org/10.1016/j.bmcl.2008.07.070CrossrefGoogle Scholar

  • [61] Dyrager, C., Wickström, M., Fridén-Saxin, M., Friberg, A., Dahlén, K., Wallén, E.A.A., Gullbo, J., Grøtli, M. and Luthman, K. Inhibitors and promoters of tubulin polymerization: synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents. Bioorg. Med. Chem. 19 (2011) 2659–2665. http://dx.doi.org/10.1016/j.bmc.2011.03.005CrossrefGoogle Scholar

  • [62] Cai, Y.-C., Zou, Y., Ye, Y.-L., Sun, H.-Y., Su, Q.-G., Wang, Z.-X., Zeng, Z.-L. and Xian L.-J. Anti-tumor activity and mechanisms of a novel vascular disrupting agent, (Z)-3,4′,5-trimethoxylstilbene-3′-O-phosphate disodium (M410). Invest. New Drugs 29 (2011) 300–311. http://dx.doi.org/10.1007/s10637-009-9366-xCrossrefGoogle Scholar

  • [63] Hatanaka, T., Fujita, K., Ohsumi, K., Nakagawa, R., Fukuda, Y., Nihei, Y., Suga, Y., Akiyama, Y. and Tsuji, T. Novel B-ring modified combretastatin analogues: syntheses and antineoplastic activity. Bioorg. Med. Chem. Lett. 8 (1998) 3371–3374. http://dx.doi.org/10.1016/S0960-894X(98)00622-2CrossrefGoogle Scholar

  • [64] Cushman, M., Nagarathnam, D., Gopal, D., Chakraborti, A.K., Lin, C.M. and Hamel, E. Synthesis and evaluation of analogues of (Z)-l-(4-methoxyphenyl)-2-(3,4,5 trimethoxyphenyl)ethene as potential cytotoxic and anti-mitotic agents. J. Med. Chem. 35 (1992) 2293–2360. http://dx.doi.org/10.1021/jm00090a021CrossrefGoogle Scholar

  • [65] Pinney, K.G., Meija, M.P., Villalobos, V.M., Rosenquist, B.E., Pettit, G.R., Verdier-Pinard, P. and Hamel, E. Synthesis and biological evaluation of aryl azide derivatives of combretastatin A-4 as molecular probes for tubulin. Bioorg. Med. Chem. 8 (2000) 2417–2425. http://dx.doi.org/10.1016/S0968-0896(00)00176-0CrossrefGoogle Scholar

  • [66] Monk, K.A., Siles, R., Hadimani, M.B., Mugabe, B.E., Ackley, J.F., Studerus, S.W., Edvardsen, K., Trawick, M.L., Garner, C.M., Rhodes, M.R., Pettit, G.R. and Pinney, K.G. Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents. Bioorg. Med. Chem. 14 (2006) 3231–3244. http://dx.doi.org/10.1016/j.bmc.2005.12.033CrossrefGoogle Scholar

  • [67] Wang, L., Woods, K.W., Li, Q., Barr, K.J., McCroskey, R.W., Hannick, S.M., Gherke, L., Credo, R.B., Hui, Y.H., Marsh, K, Warner, R., Lee, J.Y., Zielinski-Mozng, N., Frost, D., Rosenberg, S.H. and Sham, H.L. Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. J. Med. Chem. 45 (2002) 1697–1711. http://dx.doi.org/10.1021/jm010523xCrossrefGoogle Scholar

  • [68] Schobert, R., Biersack, B., Dietrich, A., Effenberger-Neidnicht, K., Knauer, S. and 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. 53 (2010) 6595–6602. http://dx.doi.org/10.1021/jm100345rCrossrefGoogle Scholar

  • [69] Bonezzi, K., Taraboletti, G., Borsotti, P., Bellina, F., Rossi, R. and Giavazzi, R. Vascular disrupting activity of tubulin-binding 1,5-diaryl-1H-imidazoles. J. Med. Chem. 52 (2009) 7906–7910. http://dx.doi.org/10.1021/jm900968sCrossrefGoogle Scholar

  • [70] Ohsumi, K., Hatanaka, T., Fujita, K., Nakagawa, R., Fukuda, Y., Nihei, Y., Suga, Y., Morinaga, Y., Akiyama, Y. and Tsuji, T. Syntheses and antitumor activity of cis-restricted combretastatins: 5-membered heterocyclic analogues. Bioorg. Med. Chem. Lett. 8 (1998) 3153–3158. http://dx.doi.org/10.1016/S0960-894X(98)00579-4Google Scholar

  • [71] Romagnoli, R., Baraldi, P.G., Brancale, A., Ricci, A., Hamel, E., Bortolozzi, R., Basso, G. and Viola, G. Convergent synthesis and biological evaluation of 2-amino-4-(3′,4′,5′-trimethoxyphenyl)-5-aryl thiazoles as microtubule targeting agents. J. Med. Chem. 54 (2011) 5144–5153. http://dx.doi.org/10.1021/jm200392pCrossrefGoogle Scholar

  • [72] Romagnoli, R., Baraldi, P.G., Salvador, M.K., Camacho, M.E., Preti, D., Tabrizi, M.A., Bassetto, M., Brancale, A., Hamel, E., Bortolozzi, R., Basso, G. and Viola, G. Synthesis and biological evaluation of 2-substituted-4-(3′,4′,5′-trimethoxyphenyl)-5-aryl thiazoles as anticancer agents. Bioorg. Med. Chem. 20 (2012) 7083–7094. http://dx.doi.org/10.1016/j.bmc.2012.10.001CrossrefGoogle Scholar

  • [73] Tron, G.C., Pagliai, F., Sel Grosso, E., Genazzani, A.A. and Sorba, G. Synthesis and cytotoxic evaluation of combretafurazans. J. Med. Chem. 48 (2005) 3260–3258. http://dx.doi.org/10.1021/jm049096oCrossrefGoogle Scholar

  • [74] Pirali, T., Busacca, S., Beltrami, L., Imovilli, D., Pagliali, F., Miglio, G., Massarotti, A., Verotta, L., Tron, G.C., Sorba, G. and Genazzani, A.A. Synthesis and cytotoxic evaluation of combretafurans, potential scaffolds for dual action of antitumoral agents. J. Med. Chem. 49 (2006) 5372–5376. http://dx.doi.org/10.1021/jm060621oCrossrefGoogle Scholar

  • [75] Theeramunkong, S., Caldarelli, A., Massarotti, A., Aprile, S., Caprioglio, S., Zaninetti, R., Teruggi, A., Pirali, T., Grosa, G. and Tron, G.C. Regioselective Suzuki coupling of dihaloheteroaromatic compounds as a rapid strategy to synthesize potent rigid combretastatin analogues. J. Med. Chem. 54 (2011) 4977–4986. http://dx.doi.org/10.1021/jm200555rCrossrefGoogle Scholar

  • [76] Zhang, W., Yang, Q., Wu, Y., Wu, L., Li, W., Qiao, F., Bao, K. and Zhang, L. Preparation of 2,3-diarylthiophene derivatives as antitumor agents. CN patent 101429189, 2009. Google Scholar

  • [77] Qiao, F., Zuo, D., Shen, X., Qi, H., Wang, H., Zhang, W. and Wu, Y. DAT-230, a novel microtubule inhibitor, exhibits potent anti-tumor activity by inducing G2/M phase arrest, apoptosis in vitro and perfusion decrease in vivo to HT-1080. Cancer Chemother. Pharmacol. 70 (2012) 259–270. http://dx.doi.org/10.1007/s00280-012-1907-xGoogle Scholar

  • [78] Liu, T., Dong, X., Xue, N., Wu, R., He, Q., Yang, B. and Hu, Y. Synthesis and biological evaluation of 3,4-biaryl-5-aminoisoxazole derivatives. Bioorg. Med. Chem. 17 (2009) 6279–6285. http://dx.doi.org/10.1016/j.bmc.2009.07.040CrossrefGoogle Scholar

  • [79] Sun, C.-N., Lin, L.-G., Yu, H.-J., Cheng, C.-Y. and Tsai, Y.-C. Synthesis and cytotoxic activities of 4,5-diarylisoxazoles. Bioorg. Med. Chem. Lett. 17 (2007) 1078–1081. http://dx.doi.org/10.1016/j.bmcl.2006.11.023CrossrefGoogle Scholar

  • [80] Schobert, R., Effenberger-Neidnicht, K. and Biersack, B. Stable combretastatin A-4 analogues with sub-nanomolar efficacy against chemoresistant HT-29 cells. Int. J. Clin. Pharmacol. Ther. 49 (2011) 71–72. Google Scholar

  • [81] Biersack, B., Effenberger, K., Schobert, R. and Ocker, M. Oxazole-bridged combretastatin A analogues with improved anticancer properties. ChemMedChem. 3 (2010) 420–427. http://dx.doi.org/10.1002/cmdc.200900477CrossrefGoogle Scholar

  • [82] Akselsen, O.W., Odlo, K., Cheng, J-J., Maccari, G., Botta, M. and Hansen, T.V. Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs of combretastatin A-1. Bioorg. Med. Chem. 20 (2012) 234–242. http://dx.doi.org/10.1016/j.bmc.2011.11.010CrossrefGoogle Scholar

  • [83] Romagnoli, R., Baraldi, P.G., Cruz-Lopez, O., Lopez-Cara, C., Carrion, M.D., Brancale, A., Hamel, E., Chen, L., Bortolozzi, R., Basso, G. and Viola, G. Synthesis and antitumor activity of 1,5-disubstituted 1,2,4-triazoles as cisrestricted combretastatin analogs. J. Med. Chem. 53 (2010) 4248–4258. http://dx.doi.org/10.1021/jm100245qCrossrefGoogle Scholar

  • [84] Odlo, K., Hentzen, J., Fournier dit Chabert, J., Ducki, S., Gani, O.A.B.S.M., Sylte, I., Skrede, M., Flørenes, V.A. and Hansen, T.V. 1,5-disubstituted 1,2,3-triazoles as cis-restricted analogues of combretastatin A-4: synthesis, molecular modeling and evaluation as cytotoxic agents and inhibitors of tubulin. Bioorg. Med. Chem. 16 (2008) 4829–4838. http://dx.doi.org/10.1016/j.bmc.2008.03.049CrossrefGoogle Scholar

  • [85] Odlo, K., Fournier-Dit-Chabert, J., Ducki, S., Gani, O.A.B.S.M., Sylte, I. and Hansen, T.V. 1,2,3-Triazole analogs of combretastatin A-4 as potential microtubule-binding agents. Bioorg. Med. Chem. 18 (2010) 6874–6885. http://dx.doi.org/10.1016/j.bmc.2010.07.032CrossrefGoogle Scholar

  • [86] Romagnoli, R., Baraldi, P.G., Salvador, M.K., Preti, D., Tabrizi, M.D., Brancale, A., Fu, X.H., Li, J., Zhang, S.Z., Hamel, E., Bortolozzi, R., Basso, G. and Viola, G. Synthesis and evaluation of 1,5-disubstituted tetrazoles as rigid analogues of combretastatin A-4 with potent antiproliferative and antitumor activity. J. Med. Chem. 54 (2012) 475–488. http://dx.doi.org/10.1021/jm2013979CrossrefGoogle Scholar

  • [87] Shirai, R., Takayama, H., Nishikawa, A., Koiso, Y. and Hashimoto, Y. Asymetric synthesis of anti-mitotic combretadioxolane with potent antitumor activity against multi-drug resistant cells. Bioorg. Med. Chem. Lett. 8 (1998) 1997–2000. http://dx.doi.org/10.1016/S0960-894X(98)00344-8CrossrefGoogle Scholar

  • [88] Pettit, R.K., Pettit, G.R., Hamel, E., Hogan, F., Moser, B.R., Wolf, S., Pon, S., Chapuis, J-C. and Schmidt, J.M. E-combretastatin and E-resveratrol structural modifications: Antimicrobial and cancer cell growth inhibitory β-E-nitrostyrenes. Bioorg. Med. Chem. 17 (2009) 6606–6612. http://dx.doi.org/10.1016/j.bmc.2009.07.076CrossrefGoogle Scholar

  • [89] Dark, G.G., Hill, S.A., Prise, V.E., Tozer, G.M., Pettit, G.R. and Chaplin, D.J. Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res. 57 (1997) 1829–1834. Google Scholar

  • [90] Hori, K., Saito, S., Nihei, Y., Suzuki, M. and Sato, Y. Antitumor effects due to irreversible stoppage of tumor tissue blood flow: evaluation of a novel combretastatin A-4 derivative, AC7700. Jpn. J. Cancer Res. 90 (1999) 1026–1038. http://dx.doi.org/10.1111/j.1349-7006.1999.tb00851.xCrossrefGoogle Scholar

  • [91] Sheng, Y., Hua, J., Pinney, K.G., Garner, C.M., Kane, R.R., Prezioso, J.A., Chaplin, D.J and Edvardsen, K. Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis. Int. J. Cancer 111 (2004) 604–610. http://dx.doi.org/10.1002/ijc.20297CrossrefGoogle Scholar

  • [92] Clémenson, C., Jouannot, E., Merino-Trigo, A., Rubin-Carrez, C. and Deutsch, E. The vascular disrupting agent ombrabulin (AVE8062) enhances the efficacy of standard therapies in head and neck squamous cell carcinoma xenograft models. Invest. New Drugs 31 (2013) 273–284. http://dx.doi.org/10.1007/s10637-012-9852-4CrossrefGoogle Scholar

  • [93] Rajak, H., Dewangan, P.K., Patel, V., Jain, D.K., Singh, A., Veerasamy, R., Sharma, P.C. and Dixit, A. Design of combretastatin A-4 analogs as tubulin targeted vascular disrupting agent with special emphasis on their cisrestricted isomers. Curr. Pharm. Des. 19 (2013) 1923–1955. http://dx.doi.org/10.2174/1381612811319100013CrossrefGoogle Scholar

  • [94] Brakenhielm, E., Cao, R. and Cao, Y. Suppression of angiogenesis, tumor growth and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J. 15 (2001) 1798–1800. Google Scholar

  • [95] Tseng, S.H., Lin, S.M., Chen, J.C., Su, Y.H., Huang, H.Y., Chen, C.K., Lin, P.Y. and Chen, Y. Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats. Clin. Cancer Res. 10 (2004) 2190–2202. http://dx.doi.org/10.1158/1078-0432.CCR-03-0105CrossrefGoogle Scholar

  • [96] Kundu, J.K. and Surh, Y.-J. Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett. 269 (2008) 243–261. http://dx.doi.org/10.1016/j.canlet.2008.03.057CrossrefGoogle Scholar

  • [97] Belleri, M., Ribatti, D., Nicoli, S., Cotelli, F., Forti, L., Vannini, V., Stivala, L.A. and Presta, M. Antiangiogenic and vascular-targeting activity of the microtubule-destabilizing trans-resveratrol derivative 3,5,4′-trimethoxystilbene. Mol. Pharmacol. 67 (2005) 1451–1459. http://dx.doi.org/10.1124/mol.104.009043CrossrefGoogle Scholar

  • [98] Alex, D., Leon, E.C., Zhang, Z.-J., Yan, G.T.H., Cheng, S.H., Leong, C.-W., Li, Z.-H., Lam, K.-H., Chan, S.-W. and Lee, S.M.-Y. Resveratrol derivative, trans-3,5,4′-trimethoxystilbene, exerts antiangiogenic and vasculardisrupting effects in zebrafish through the downregulation of VEGFR2 and cell-cycle modulation. J. Cell. Biochem. 109 (2010) 339–346. Google Scholar

  • [99] Folkes, L.K., Christlieb, M., Madej, E., Stratford, M.R.L. and Wardman, P. Oxidative metabolism of combretastatin A-1 produces quinone intermediates with the potential to bind to nucleophiles and to enhance oxidative stress via free radicals. Chem. Res. Toxicol. 20 (2007) 1885–1894. http://dx.doi.org/10.1021/tx7002195CrossrefGoogle Scholar

  • [100] Rice, L., Pampo, C., Lepler, S., Rojiani, A.M. and Siemann, D.W. Support of a free radical mechanism for enhanced antitumor efficacy of the microtubule disruptor OXi4503. Microvasc. Res. 81 (2011) 44–51. http://dx.doi.org/10.1016/j.mvr.2010.10.003CrossrefGoogle Scholar

  • [101] Madlambayan, G.J., Meacham, A.M., Hosaka, K., Mir, S., Jorgensen, M., Scott, E.W., Siemann, D.W. and Cogle, C.R. Leukemia regression by vascular disruption and anti-angiogenic therapy. Blood 116 (2010) 1539–1547. http://dx.doi.org/10.1182/blood-2009-06-230474CrossrefGoogle Scholar

  • [102] Peláez, R., López, J.L. and Medarde, M. Application of chemoinformatic tools for the analysis of virtual screening studies of tubulin inhibitors. Advances in Soft Computing 44 (2007) 411–441. http://dx.doi.org/10.1007/978-3-540-74972-1_53CrossrefGoogle Scholar

  • [103] Nguyen, T.L., McGrath, C., Hermone, A.R., Burnett, C.J., Zharevitz, D.W., Day, B.W., Wipf, P., Hamel, E. and Gussio, R. A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach. J. Med. Chem. 48 (2005) 6107–6116. http://dx.doi.org/10.1021/jm050502tCrossrefGoogle Scholar

  • [104] Massarotti, A., Theeramunkong, S., Mesenzani, O., Caldarelli, A., Genazzani, A.A. and Tron, G.C. Identification of novel antitubulin agents by using a virtual screening approach based on 7-point pharmacophore model of the tubulin colchicine site. Chem. Biol. Drug Des. 78 (2011) 913–922. http://dx.doi.org/10.1111/j.1747-0285.2011.01245.xCrossrefGoogle Scholar

  • [105] Kim, N.D., Park, E.-S., Kim, Y.H., Moon, S.K., Lee, S. S., Ahn, S.K., Yu, D.-Y., No, K.T. and Kim, K.-H. Structure-based virtual screening of novel tubulin inhibitors and their characterization as anti-mitotic agents. Bioorg. Med. Chem. 18 (2010) 7092–7100. http://dx.doi.org/10.1016/j.bmc.2010.07.072CrossrefGoogle Scholar

  • [106] Massarotti, A., Coluccia, A., Silvestri, R., Sorba, G. and Brancale, A. The tubulin colchicine domain: a molecular modeling perspective. Chem. Med. Chem. 7 (2012) 33–42. CrossrefGoogle Scholar

  • [107] Romagnoli, R., Baraldi, P.G., Carrion, M.D., Cruz-Lopez, O., Cara, C.L., Tolomeo, M., Grimaudo, S., Di Cristina, A., Pipitone, M.R., Balzarini, J., Kandil, S., Brancale, A., Srkar, T. and Hamel, E. Synthesis and biological evaluation of 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)-6-substituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives as anti-mitotic agents and inhibitors of tubulin polymerization. Bioorg. Med. Chem. Lett. 18 (2008) 5041–5045. http://dx.doi.org/10.1016/j.bmcl.2008.08.006Google Scholar

  • [108] Ruan, B.-F., Lu, X., Tang, J.-F., Wei, Y., Wang, X.-L., Zhang, Y.-B., Wang, L.-S. and Zhu, H.-L. Synthesis, biological evaluation, and molecular docking studies of resveratrol derivatives possessing chalcone moiety as potential antitubulin agents. Bioorg. Med. Chem. 19 (2011) 2688–2695. http://dx.doi.org/10.1016/j.bmc.2011.03.001CrossrefGoogle Scholar

  • [109] Kim, S., Min, S.Y., Lee, S.K., Cho, W.-J. Comparative molecular field analysis study of stilbene derivatives active against A549 lung carcinoma. Chem. Pharm. Bull. 51 (2003) 516–521. http://dx.doi.org/10.1248/cpb.51.516CrossrefGoogle Scholar

  • [110] Chiang, Y.K., Kuo, C.C., Wu, Y.S., Chen, C.T., Coumar, M.S., Wu, J.S., Hsieh, H.P., Chang, C.Y., Jseng, H.Y., Wu, M.H., Leou, J.S., Song, J.S., Chang, J.Y., Lyu, P.C., Chao, Y.S. and Wu, S.Y. Generation of ligandbased pharmacophore model and virtual screening for identification of tubulin inhibitors with potent anticancer activity. J. Med. Chem. 52 (2009) 4221–4233. http://dx.doi.org/10.1021/jm801649yCrossrefGoogle Scholar

  • [111] Tseng, C.Y., Mane, J.Y., Winter, P., Johnson, L., Huzil, T., Izbicka, E., Luduena, R.F. and Tuszynski, J.A. Quantitative analysis of the effect of tubulin isotype expression on sensitivity of cancer cell lines to a set of novel colchicine derivatives. Mol. Cancer 30 (2010) 131–150. http://dx.doi.org/10.1186/1476-4598-9-131CrossrefGoogle Scholar

  • [112] Tuszynski, J.A., Craddock, T.J., Mane, J.Y., Barakat, K., Tseng, C.Y., Gajewski, M., Winter, P., Alisaraie, L., Patterson, J., Carpenter, E., Wang, W., Deyholos, M.K., Li, L., Sun, X., Zhang, Y. and Wong, G.K. Modeling the yew tree tubulin and a comparison of its interaction with Paclitaxel to human tubulin. Pharm. Res. 29 (2012) 3007–3021. http://dx.doi.org/10.1007/s11095-012-0829-yCrossrefGoogle Scholar

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Published Online: 2013-07-27

Published in Print: 2013-09-01

Citation Information: Cellular and Molecular Biology Letters, Volume 18, Issue 3, Pages 368–397, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-013-0094-z.

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