Recent Advances on Small-Molecule Tubulin Inhibitors

doi:10.21127/yaoyimr20200024

Medicine Research ›› 2021, Vol. 5 ›› Issue (1): 200024-200024.DOI: 10.21127/yaoyimr20200024

所属专题： Anticancer Agents

• • 上一篇

Recent Advances on Small-Molecule Tubulin Inhibitors

Xiu-Li Sun,^a,b Yin-Rong Xie,^a,b Ning Zhang,^a,b Cheng-Ting Zi,^*,a,c Xuan-Jun Wang,^*,a,c and Jun Sheng^*,a

a Key Laboratory of Pu-erh Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, Yunnan 650201, China;
b College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan 650201, China;
c College of Science, Yunnan Agricultural University, Kunming, Yunnan 650201, China

收稿日期:2020-12-29 修回日期:2021-02-21 出版日期:2021-01-20 发布日期:2021-01-20
通讯作者: *,Email: zichengting@126.com (C. Z.), xuanjunwang@qq.com (X. W.) and shengj@ynau.edu.cn (J. S.)
基金资助:

Recent Advances on Small-Molecule Tubulin Inhibitors

Xiu-Li Sun,^a,b Yin-Rong Xie,^a,b Ning Zhang,^a,b Cheng-Ting Zi,^*,a,c Xuan-Jun Wang,^*,a,c and Jun Sheng^*,a

a Key Laboratory of Pu-erh Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, Yunnan 650201, China;
b College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan 650201, China;
c College of Science, Yunnan Agricultural University, Kunming, Yunnan 650201, China

Received:2020-12-29 Revised:2021-02-21 Online:2021-01-20 Published:2021-01-20
Contact: *,Email: zichengting@126.com (C. Z.), xuanjunwang@qq.com (X. W.) and shengj@ynau.edu.cn (J. S.)
Supported by:

摘要/Abstract

摘要： Microtubules are heterodimers composed of α/β tubulin and make up the cytoskeleton. It plays an important role in maintaining cellular morphology, cell division, signal transduction and other processes. At present, six tubulin inhibitor binding sites have been identified. The inhibitors can be divided into two categories: a type of microtubule polymerization agent includes colchicine site, vinblastine site, maytansine site and prionetin site inhibitors; another category is paclitaxel and laulimalide/peloruside binding site inhibitors are called microtubule depolymerization. Herein, we summarize relevant inhibitors acting on these 6 sites and their research status. With extensive research on tubulin binding sites and inhibitors, anti-tumor tubulin inhibitors will possess very broad clinical prospects.

关键词: microtubule, tubulin, binding site, inhibitors

Abstract: Microtubules are heterodimers composed of α/β tubulin and make up the cytoskeleton. It plays an important role in maintaining cellular morphology, cell division, signal transduction and other processes. At present, six tubulin inhibitor binding sites have been identified. The inhibitors can be divided into two categories: a type of microtubule polymerization agent includes colchicine site, vinblastine site, maytansine site and prionetin site inhibitors; another category is paclitaxel and laulimalide/peloruside binding site inhibitors are called microtubule depolymerization. Herein, we summarize relevant inhibitors acting on these 6 sites and their research status. With extensive research on tubulin binding sites and inhibitors, anti-tumor tubulin inhibitors will possess very broad clinical prospects.

Key words: microtubule, tubulin, binding site, inhibitors

中图分类号:

Xiu-Li Sun, Yin-Rong Xie, Ning Zhang, Cheng-Ting Zi, Xuan-Jun Wang, and Jun Sheng. Recent Advances on Small-Molecule Tubulin Inhibitors[J]. Medicine Research, 2021, 5(1): 200024-200024.

参考文献

[1] Luduena, R. F. A hypothesis on the origin and evolution of tubulin. Int. Rev. Cell Mol. Biol. 2013, 302, 41–185.
[2] Dumontet, C.; Jordan, M. A. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat. Rev. Drug Discov. 2010, 9, 790–803.
[3] Parker, A. L.; Teo, W. S.; Mccarroll, J. A.; Kavallaris, M. An Emerging Role for Tubulin Isotypes in Modulating Cancer Biology and Chemotherapy Resistance. Int. J. Mol. Sci. 2017, 18, 1434.
[4] Issell, B. F.; Crooke, S. T. Maytansine. Cancer Treat. Rev. 1978, 5, 199–207.
[5] Li, L.; Jiang S.; Li, X.; Liu, Y.; Su, J.; Chen, J. Recent advances in trimethoxyphenyl (TMP) based tubulin inhibitors targeting the colchicine binding site. Eur. J. Med. Chem. 2018, 151, 482–494.
[6] Coulup, S. K.; Georg, G. I. Revisiting microtubule targeting agents: alpha-Tubulin and the pironetin binding site as unexplored targets for cancer therapeutics. Bioorg. Med. Chem. Lett. 2019, 29, 1865–1873.
[7] Balkrishna, A.; Das, S. K.; Pokhrel, S.; Joshi, A.; Verma, S.; Sharma, V. K.; Sharma, V.; Sharma, N.; Joshi, C. S. Colchicine: Isolation, LC-MS QTof Screening, and Anticancer Activity Study of Gloriosa superba Seeds. Molecules 2019, 24, 2772.
[8] Goto, H.; Yano, S.; Zhang, H.; Matsumori, Y.; Ogawa, H.; Blakey, D. C.; Sone, S. Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice. Cancer Res. 2002, 62, 3711–3715.
[9] Combes, S.; Barbier, P.; Douillard, S.; McLeer-Florin, A.; Bourgarel-Rey, V.; Pierson, J. T.; Fedorov, A. Y.; Finet, J. P.; Boutonnat, J.; Peyrot, V. Synthesis and Biological Evaluation of 4-Arylcoumarin Analogues of Combretastatins. Part 2. J. Med. Chem. 2011, 54, 3153–3162.
[10] Kim, T. J.; Ravoori, M.; Landen, C. N.; Kamat, A. A.; Han, L, Y.; Lu, C.; Lin, Y. G.; Merritt, W. M.; Jennings, N.; Spannuth, W. A. Antitumor and antivascular effects of AVE8062 in ovarian carcinoma. Cancer Res. 2007, 67, 9337–9345.
[11] Hori, K.; Saito, S. Induction of tumour blood flow stasis and necrosis: a new function for epinephrine similar to that of combretastatin A-4 derivative AVE8062 (AC7700). Br. J. Cancer. 2004, 90, 549–553.
[12] Cortese, F.; Bhattacharyya, B.; Wolff, J. Podophyllotoxin as a probe for the colchicine binding site of tubulin. J. Biol. Chem. 1977, 252, 1134–1140.
[13] Verdier-Pinard, P.; Sitachitta, N.; Rossi, J. V.; Sackett, D. L.; Gerwick, W. H.; Hamel, E. Biosynthesis of Radiolabeled Curacin A and Its Rapid and Apparently Irreversible Binding to the Colchicine Site of Tubulin. Arch. Biochem. Biophys. 1999, 370, 51–58.
[14] Kim, D. Y.; Kim, K. H.; Kim, N. D.; Lee, K. Y.; Han, C. K.; Yoon, J. H.; Moon, S. K.; Lee, S. S.; Seong, B. L. Design and biological evaluation of novel tubulin inhibitors as antimitotic agents using a pharmacophore binding model with tubulin. J. Med. Chem. 2006, 49, 5664.
[15] Risinger, A. L.; Westbrook, C. D.; Encinas, A.; Mulbaier, M.; Schultes, C. M.; Wawro, S.; Lewis, J. D.; Janssen, B.; Giles, F. J.; Mooberry, S. L. ELR510444, a novel microtubule disruptor with multiple mechanisms of action. J. Pharmacol. Exp. Ther. 2011, 336, 652–660.
[16] Kuo, C. C.; Hsieh, H. P.; Pan, W. Y.; Chen, C. P.; Liou, J. P; Lee, S. J.; Chang, Y. L.; Chen, L. T.; Chen, C. T.; Chang, J. Y. BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res. 2004, 64, 4621–4628.
[17] Beckers, T.; Reissmann, T.; Schmidt, M.; Burger, A. M.; Fiebig, H. H.; Vanhoefer, U.; Pongratz, H.; Hufsky, H.; Hockemeyer, J.; Frieser, M.; Mahboobi, S. 2-Aroylindoles, a novel class of potent, orally active small molecule tubulin inhibitors. Cancer Res, 2002, 62, 3113–3119.
[18] Banerjee, A.; Luduena, R. F. Kinetics of colchicine binding to purified beta-tubulin isotypes from bovine brain. J. Biol. Chem.1992, 267,13335–13339.
[19] Singer, W. D.; Jordan, M. A.; Wilson, L.; Himes, R. H. Binding of vinblastine to stabilized microtubules. Mol. Pharmacol. 1989, 36, 366–370.
[20] Lobert, S.; Vulevic, B.; Correia, J. J.; Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine, and vinorelbine. Biochemistry 1996, 35, 6806.
[21] Matesanz, R.; Barasoain, I.; Yang, C. G.; Wang, L.; Li, X.; Inés, C. d.; Coderch, C.; Gago, F.; Barbero, J. J.; Andreu, J. M.; Fang, W. S.; Díaz, J. F. Optimization of Taxane Binding to Microtubules: Binding Affinity Dissection and Incremental Construction of a High-Affinity Analog of Paclitaxel. Cell Chem. Biol. 2008, 15, 573–585.
[22] Cormier, A.; Marchand, M.; Ravelli, R. B. G.; Knossow, M.; Gigant, B. Structural insight into the inhibition of tubulin by vinca domain peptide ligands. EMBO Rep. 2008, 9, 1101–1106.
[23] Chao, M. W.; Lai, M. J.; Liou, J. P.; Chang, Y. L.; Wang, J. C.; Pan, S. L.; Teng, C. M. The synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo. J. Hematol. Oncol. 2015, 8, 82.
[24] Bai, R. L.; Paull, K. D.; Herald, C. L.; Malspeis, L.; Pettit, G. R.; Hamel, E. Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J. Biol. Chem. 1991, 266, 15882–15889.
[25] Jordan, M. A.; Kamath, K.; Manna, T.; Okouneva, T.; Miller, H. P.; Davis, C.; Littlefield, B. A.; Wilson, L. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol. Cancer Ther. 2005, 4, 1086–1095.
[26] Kuznetsov, G.; TenDyke, K.; Towle, M. J.; Cheng, H. S.; Liu, J. K.; Marsh, J. P.; Schiller, S. E. R.; Spyvee, M. R.; Yang, H.; Seletsky, B. M.; Shaffer, C. J.; Marceau, V.; Yao, Y.; Suh, E.M.; Campagna, S.; Fang, F. G.; Kowalczyk, J.; Lottlefield, B. A. Tubulin-based antimitotic mechanism of E7974, a novel analogue of the marine sponge natural product hemiasterlin. Mol. Cancer Ther. 2009, 8, 2852–2860.
[27] Aherne, G. W.; Hardcastle, A.; Valenti, M.; Bryant, A.; Rogers, P.; Pettit, G. R.; Srirangam, J. K.; Kelland, L. R. Antitumour evaluation of dolastatins 10 and 15 and their measurement in plasma by radioimmunoassay. Cancer Chemother. Pharmacol. 1996, 38, 225–232.
[28] Prota, A. E.; Bargsten, K.; Diaz, J. F.; Marsh, M.; Cuevas, C.; Liniger, M.; Neuhaus, C.; Andreu, J. M.; Altmann, K. H.; Steinmetz, M. O. A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 13817–13821.
[29] Navarrete, K. R.; Jimenez, V. A. Interdimeric Curvature in Tubulin-Tubulin Complexes Delineates the Microtubule- Destabilizing Properties of Plocabulin. J. Chem. Inf. Model. 2020, 60, 4076–4084.
[30] Kondoh, M.; Usui, T.; Kobayashi, S.; Tsuchiya, K.; Nishikawa, K.; Nishikiori, T.; Mayumi, T.; Osada, H. Cell cycle arrest and antitumor activity of pironetin and its derivatives. Cancer Lett. 1998, 126, 29–32.
[31] Schiff, P. B.; Fant, J.; Horwitz, S. B. Promotion of microtubule assembly in vitro by taxol. Nature 1979, 277, 655–657.
[32] Mielgo, A.; Torres, V. A.; Clair, K.; Barbero, S.; Stupack, D. G. Paclitaxel promotes a caspase 8-mediated apoptosis through death effector domain association with microtubules. Oncogene 2009, 28, 3551–3562.
[33] Rothermel, J.; Wartmann, M.; Chen, T.; Hohneker, J. EPO906 (epothilone B): a promising novel microtubule stabilizer. Semin. Oncol. 2003, 30, 51–55.
[34] ter Haar, E.; Kowalski, R. J.; Hamel, E.; Lin, C. M.; Longley, R. E.; Gunasekera, S. P.; Rosenkranz, H. S.; Day, B. W. Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochem. 1996, 35, 243–250.
[35] Mooberry, S. L.; Tien, G.; Hernandez, A. H.; Plubrukarn, A.; Davidson, B. S. Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. Cancer Res. 1999, 59, 653–660.
[36] Hood, K. A.; West, L. M.; Rouwé, B.; Northcote, P. T.; Berridge, M. V.; Wakefield, S. J.; Miller, J. H. Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule- stabilizing activity. Cancer Res. 2002, 62, 3356–3360.
[37] Zúñiga, M. A.; Alderete, J. B.; Jaña, G. A.; Fernandez, P. A.; Ramos, M. J.; Jiménez, V. A. Modulation of lateral and longitudinal interdimeric interactions in microtubule models by Laulimalide and Peloruside A association: A molecular modeling approach on the mechanism of microtubule stabilizing agents. Chem. Biol. Drug Des. 2018, 91, 1042–1055.

Recent Advances on Small-Molecule Tubulin Inhibitors

Recent Advances on Small-Molecule Tubulin Inhibitors

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics