Generic placeholder image

Anti-Infective Agents

Author(s): Adarsh Sahu*

DOI: 10.2174/2211352519666211119090754

DownloadDownload PDF Flyer Cite As
Combretastatin Derivatives as Microtubule Inhibitors of Colchicines Binding Site

Article ID: e191121198115 Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

The colchicine binding site in microtubules is the most flourishing target for anticancer treatment. Microtubule inhibitor drugs, including paclitaxel and vinca alkaloids, have been considered to exert their activity primarily by increasing or decreasing the cellular microtubule mass. This review describes the microtubular assembly along with the combretastatin derivatives as microtubules inhibitors, the structures of compounds known to interact with colchicines binding sites, and their possible mechanism of action. Additionally, the utility of other heterocyclic rings and their combretastatin derivatives in treating cancer is also discussed. Colchicines binding site represents a stimulating new molecular target in the design of combretastatin drugs.

Keywords: Combrestatin, colchicine, microtubules, anticancer, aplha-tubulin, betatubulin.

[1]
Islam, M.N.; Iskander, M.N. Microtubulin binding sites as target for developing anticancer agents. Mini Rev. Med. Chem., 2004, 4(10), 1077-1104.
[http://dx.doi.org/10.2174/1389557043402946] [PMID: 15579115]
[2]
Dong, M.; Liu, F.; Zhou, H.; Zhai, S.; Yan, B. Novel natural product-and privileged scaffold-based tubulin inhibitors targeting the colchi-cine binding site. Molecules, 2016, 21(10), 1375.
[http://dx.doi.org/10.3390/molecules21101375] [PMID: 27754459]
[3]
Krause, W. Resistance to anti-tubulin agents: From vinca alkaloids to epothilones. Cancer Drug Resist., 2019, 2(1), 82-106.
[http://dx.doi.org/10.20517/cdr.2019.06]
[4]
Abdal Dayem, A.; Hossain, M.K.; Lee, S.B.; Kim, K.; Saha, S.K.; Yang, G.M.; Choi, H.Y.; Cho, S.G. The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles. Int. J. Mol. Sci., 2017, 18(1), 120.
[http://dx.doi.org/10.3390/ijms18010120] [PMID: 28075405]
[5]
Rogowski, K.; Van Dijk, J.; Magiera, M.M.; Bosc, C.; Deloulme, J.C.; Bosson, A.; Peris, L.; Gold, N.D.; Lacroix, B.; Grau, M.B.; Bec, N. A family of protein-deglutamylating enzymes associated with neurodegeneration. Cell, 2010, 143(4), 564-578.
[6]
Desai, A.; Mitchison, T.J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol., 1997, 13(1), 83-117.
[http://dx.doi.org/10.1146/annurev.cellbio.13.1.83] [PMID: 9442869]
[7]
Kingston, D.G. Tubulin-interactive natural products as anticancer agents. J. Nat. Prod., 2009, 72(3), 507-515.
[http://dx.doi.org/10.1021/np800568j] [PMID: 19125622]
[8]
Dumontet, C.; Jordan, M.A. Microtubule-binding agents: A dynamic field of cancer therapeutics. Nat. Rev. Drug Discov., 2010, 9(10), 790-803.
[http://dx.doi.org/10.1038/nrd3253] [PMID: 20885410]
[9]
Grisham, R.; Ky, B.; Tewari, K.S.; Chaplin, D.J.; Walker, J. Clinical trial experience with CA4P anticancer therapy: Focus on efficacy, car-diovascular adverse events, and hypertension management. Gynecol. Oncol. Res. Pract., 2018, 5(1), 1-10.
[http://dx.doi.org/10.1186/s40661-017-0058-5] [PMID: 29318022]
[10]
Caplow, M.; Fee, L. Dissociation of the tubulin dimer is extremely slow, thermodynamically very unfavorable, and reversible in the ab-sence of an energy source. Mol. Biol. Cell, 2002, 13(6), 2120-2131.
[http://dx.doi.org/10.1091/mbc.e01-10-0089] [PMID: 12058074]
[11]
Fees, C.P.; Moore, J.K. Regulation of microtubule dynamic instability by the carboxy-terminal tail of β-tubulin. Life Sci. Alliance, 2018, 1(2), e201800054.
[http://dx.doi.org/10.26508/lsa.201800054] [PMID: 29963657]
[12]
Jordan, M.A. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr. Med. Chem. Anticancer Agents, 2002, 2(1), 1-17.
[http://dx.doi.org/10.2174/1568011023354290] [PMID: 12678749]
[13]
Mitchison, T.; Kirschner, M. Dynamic instability of microtubule growth. Nature, 1984, 312(5991), 237-242.
[14]
Farache, D.; Emorine, L.; Haren, L.; Merdes, A. Assembly and regulation of γ-tubulin complexes. Open Biol., 2018, 8(3), 170266.
[http://dx.doi.org/10.1098/rsob.170266] [PMID: 29514869]
[15]
Zefirova, O.N.; Diikov, A.G.; Zyk, N.V.; Zefirov, N.S. Ligands of the colchicine site of tubulin: A common pharmacophore and new structural classes. Russ. Chem. Bull., 2007, 56(4), 680-688.
[http://dx.doi.org/10.1007/s11172-007-0106-0]
[16]
Da, C.; Mooberry, S.L.; Gupton, J.T.; Kellogg, G.E. How to deal with low-resolution target structures: Using SAR, ensemble docking, hy-dropathic analysis, and 3D-QSAR to definitively map the α β-tubulin colchicine site. J. Med. Chem., 2013, 56(18), 7382-7395.
[http://dx.doi.org/10.1021/jm400954h] [PMID: 23961916]
[17]
Pryor, D.E.; O’Brate, A.; Bilcer, G.; Díaz, J.F.; Wang, Y.; Wang, Y.; Kabaki, M.; Jung, M.K.; Andreu, J.M.; Ghosh, A.K.; Giannakakou, P.; Hamel, E. 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(29), 9109-9115.
[http://dx.doi.org/10.1021/bi020211b] [PMID: 12119025]
[18]
Pettit, G.R.; Grealish, M.P.; Herald, D.L.; Boyd, M.R.; Hamel, E.; Pettit, R.K. Antineoplastic agents. 443. Synthesis of the cancer cell growth inhibitor hydroxyphenstatin and its sodium diphosphate prodrug. J. Med. Chem., 2000, 43(14), 2731-2737.
[http://dx.doi.org/10.1021/jm000045a] [PMID: 10893310]
[19]
Ghinet, A.; Tourteau, A.; Rigo, B.; Stocker, V.; Leman, M.; Farce, A.; Dubois, J.; Gautret, P. Synthesis and biological evaluation of fluoro analogues of antimitotic phenstatin. Bioorg. Med. Chem., 2013, 21(11), 2932-2940.
[http://dx.doi.org/10.1016/j.bmc.2013.03.064] [PMID: 23618708]
[20]
Gaukroger, K.; Hadfield, J.A.; Lawrence, N.J.; Nolan, S.; McGown, A.T. Structural requirements for the interaction of combretastatins with tubulin: How important is the trimethoxy unit? Org. Biomol. Chem., 2003, 1(17), 3033-3037.
[http://dx.doi.org/10.1039/B306878A] [PMID: 14518125]
[21]
Ghinet, A.; Abuhaie, C.M.; Gautret, P.; Rigo, B.; Dubois, J.; Farce, A.; Belei, D.; Bîcu, E. Studies on indolizines. Evaluation of their bio-logical properties as microtubule-interacting agents and as melanoma targeting compounds. Eur. J. Med. Chem., 2015, 89, 115-127.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.041] [PMID: 25462232]
[22]
Ding, X.; Zhang, Z.; Li, S.; Wang, A. Combretastatin A4 phosphate induces programmed cell death in vascular endothelial cells. Oncol. Res., 2011, 19(7), 303-309.
[http://dx.doi.org/10.3727/096504011X13079697132790] [PMID: 21936400]
[23]
Penthala, N.R.; Sonar, V.N.; Horn, J.; Leggas, M.; Yadlapalli, J.S.K.; Crooks, P.A. Synthesis and evaluation of a series of benzothiophene acrylonitrile analogs as anticancer agents. MedChemComm, 2013, 4(7), 1073-1078.
[http://dx.doi.org/10.1039/c3md00130j] [PMID: 23956835]
[24]
Suman, P.; Murthy, T.R.; Rajkumar, K.; Srikanth, D.; Dayakar, Ch.; Kishor, C.; Addlagatta, A.; Kalivendi, S.V.; Raju, B.C. Synthesis and structure-activity relationships of pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles as potent inhibitors of tubulin polymerization. Eur. J. Med. Chem., 2015, 90, 603-619.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.063] [PMID: 25499929]
[25]
Reddy, M.A.; Jain, N.; Yada, D.; Kishore, C.; Vangala, J.R.P.; P., Surendra R.; Addlagatta, A.; Kalivendi, S.V.; Sreedhar, B. Design and syn-thesis of resveratrol-based nitrovinylstilbenes as antimitotic agents. J. Med. Chem., 2011, 54(19), 6751-6760.
[http://dx.doi.org/10.1021/jm200639r] [PMID: 21851083]
[26]
Madadi, N.R.; Penthala, N.R.; Howk, K.; Ketkar, A.; Eoff, R.L.; Borrelli, M.J.; Crooks, P.A. Synthesis and biological evaluation of novel 4,5-disubstituted 2H-1,2,3-triazoles as cis-constrained analogues of combretastatin A-4. Eur. J. Med. Chem., 2015, 103, 123-132.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.041] [PMID: 26352674]
[27]
Wang, S.F.; Yin, Y.; Zhang, Y.L.; Mi, S.W.; Zhao, M.Y.; Lv, P.C.; Wang, B.Z.; Zhu, H.L. Synthesis, biological evaluation and 3D-QSAR studies of novel 5-phenyl-1H-pyrazol cinnamamide derivatives as novel antitubulin agents. Eur. J. Med. Chem., 2015, 93, 291-299.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.018] [PMID: 25703297]
[28]
Lee, H.Y.; Chang, C.Y.; Lai, M.J.; Chuang, H.Y.; Kuo, C.C.; Chang, C.Y.; Chang, J.Y.; Liou, J.P. Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes. Bioorg. Med. Chem., 2015, 23(15), 4230-4236.
[http://dx.doi.org/10.1016/j.bmc.2015.06.043] [PMID: 26160020]
[29]
Lai, M.J.; Lee, H.Y.; Chuang, H.Y.; Chang, L.H.; Tsai, A.C.; Chen, M.C.; Huang, H.L.; Wu, Y.W.; Teng, C.M.; Pan, S.L.; Liu, Y.M.; Mehndiratta, S.; Liou, J.P. N-Sulfonyl-aminobiaryls as antitubulin agents and inhibitors of signal transducers and activators of transcrip-tion 3 (STAT3) signaling. J. Med. Chem., 2015, 58(16), 6549-6558.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00659] [PMID: 26241032]
[30]
Madadi, N.R.; Zong, H.; Ketkar, A.; Zheng, C.; Penthala, N.R.; Janganati, V.; Bommagani, S.; Eoff, R.L.; Guzman, M.L.; Crooks, P.A. Synthesis and evaluation of a series of resveratrol analogues as potent anti-cancer agents that target tubulin. Med. Chem. Comm., 2015, 6(3), 788-794.
[http://dx.doi.org/10.1039/C4MD00478G] [PMID: 26257861]
[31]
Kamal, A.; Reddy, V.S.; Shaik, A.B.; Kumar, G.B.; Vishnuvardhan, M.V.P.S.; Polepalli, S.; Jain, N. Synthesis of (Z)-(arylamino)-pyrazolyl/isoxazolyl-2-propenones as tubulin targeting anticancer agents and apoptotic inducers. Org. Biomol. Chem., 2015, 13(11), 3416-3431.
[http://dx.doi.org/10.1039/C4OB02449D] [PMID: 25661328]
[32]
Kamal, A.; Subba Rao, A.V.; Vishnuvardhan, M.V.P.S.; Srinivas Reddy, T.; Swapna, K.; Bagul, C.; Subba Reddy, N.V.; Srinivasulu, V. Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents. Org. Biomol. Chem., 2015, 13(17), 4879-4895.
[http://dx.doi.org/10.1039/C5OB00232J] [PMID: 25765224]
[33]
Soussi, M.A.; Provot, O.; Bernadat, G.; Bignon, J.; Desravines, D.; Dubois, J.; Brion, J.D.; Messaoudi, S.; Alami, M. IsoCom-bretaQuinazolines: Potent cytotoxic agents with antitubulin activity. ChemMedChem, 2015, 10(8), 1392-1402.
[http://dx.doi.org/10.1002/cmdc.201500069] [PMID: 26076053]
[34]
Galli, U.; Travelli, C.; Aprile, S.; Arrigoni, E.; Torretta, S.; Grosa, G.; Massarotti, A.; Sorba, G.; Canonico, P.L.; Genazzani, A.A.; Tron, G.C. Design, synthesis, and biological evaluation of combretabenzodiazepines: a novel class of anti-tubulin agents. J. Med. Chem., 2015, 58(3), 1345-1357.
[http://dx.doi.org/10.1021/jm5016389] [PMID: 25584687]
[35]
Duan, Y.T.; Man, R.J.; Tang, D.J.; Yao, Y.F.; Tao, X.X.; Yu, C.; Liang, X.Y.; Makawana, J.A.; Zou, M.J.; Wang, Z.C.; Zhu, H.L. Design, synthesis and antitumor activity of novel link-bridge and B-ring modified combretastatin A-4 (CA-4) analogues as potent antitubulin agents. Sci. Rep., 2016, 6(1), 25387.
[http://dx.doi.org/10.1038/srep25387] [PMID: 27138035]
[36]
Swanton, C.; Caldas, C. Molecular classification of solid tumours: Towards pathway-driven therapeutics. Br. J. Cancer, 2009, 100(10), 1517-1522.
[http://dx.doi.org/10.1038/sj.bjc.6605031] [PMID: 19367275]
[37]
Finkelstein, Y.; Aks, S.E.; Hutson, J.R.; Juurlink, D.N.; Nguyen, P.; Dubnov-Raz, G.; Pollak, U.; Koren, G.; Bentur, Y. Colchicine poison-ing: The dark side of an ancient drug. Clin. Toxicol. (Phila.), 2010, 48(5), 407-414.
[http://dx.doi.org/10.3109/15563650.2010.495348] [PMID: 20586571]
[38]
Cheng, J.; Tsuda, M.; Okolotowicz, K.; Dwyer, M.; Bushway, P.J.; Colas, A.R.; Lancman, J.J.; Schade, D.; Perea-Gil, I.; Bruyneel, A.A.N.; Lee, J.; Vadgama, N.; Quach, J.; McKeithan, W.L.; Biechele, T.L.; Wu, J.C.; Moon, R.T.; Si Dong, P.D.; Karakikes, I.; Cashman, J.R.; Mer-cola, M. Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness. Cell Chem. Biol., 2021, 28(5), 625-635.e5.
[http://dx.doi.org/10.1016/j.chembiol.2021.01.001] [PMID: 33503403]
[39]
Khan, A.H.; Bloom, J.S.; Faridmoayer, E.; Smith, D.J. Genetic screening reveals a link between Wnt signaling and antitubulin drugs. Pharmacogenomics J., 2016, 16(2), 164-172.
[http://dx.doi.org/10.1038/tpj.2015.50] [PMID: 26149735]
[40]
Kashiwabara, K.; Yamane, H.; Tanaka, H. Toxicity and prognosis in overweight and obese women with lung cancer receiving carboplatin-paclitaxel doublet chemotherapy. Cancer Invest., 2013, 31(4), 251-257.
[http://dx.doi.org/10.3109/07357907.2013.784778] [PMID: 23607633]
[41]
Porcù, E.; Persano, L.; Ronca, R.; Mitola, S.; Bortolozzi, R.; Romagnoli, R.; Oliva, P.; Basso, G.; Viola, G. The novel antitubulin agent TR-764 strongly reduces tumor vasculature and inhibits HIF-1 α activation. Sci. Rep., 2016, 6(1), 1-15.
[http://dx.doi.org/10.1038/srep27886] [PMID: 28442746]
[42]
Dong, Q.; Wang, Z.; Zhang, K.; Yu, H.; Huang, P.; Liu, X.; Zhou, Y.; Chen, N.; Song, B. Easily accessible polymer additives for tuning the crystal-growth of perovskite thin-films for highly efficient solar cells. Nanoscale, 2016, 8(10), 5552-5558.
[http://dx.doi.org/10.1039/C6NR00206D] [PMID: 26887633]
[43]
Bradeen, H.A.; Eide, C.A.; O’Hare, T.; Johnson, K.J.; Willis, S.G.; Lee, F.Y.; Druker, B.J.; Deininger, M.W. Comparison of imatinib mesyl-ate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. Blood, 2006, 108(7), 2332-2338.
[http://dx.doi.org/10.1182/blood-2006-02-004580] [PMID: 16772610]
[44]
Aceves-Luquero, C.I.; Agarwal, A.; Callejas-Valera, J.L.; Arias-González, L.; Esparís-Ogando, A.; del Peso Ovalle, L.; Bellón-Echeverria, I.; de la Cruz-Morcillo, M.A.; Galán Moya, E.M.; Moreno Gimeno, I.; Gómez, J.C.; Deininger, M.W.; Pandiella, A.; Sánchez Prieto, R. ERK2, but not ERK1, mediates acquired and “de novo” resistance to imatinib mesylate: implication for CML therapy. PLoS One, 2009, 4(7), e6124.
[http://dx.doi.org/10.1371/journal.pone.0006124] [PMID: 19568437]
[45]
Scatena, C.D.; Stewart, Z.A.; Mays, D.; Tang, L.J.; Keefer, C.J.; Leach, S.D.; Pietenpol, J.A. Mitotic phosphorylation of Bcl-2 during nor-mal cell cycle progression and Taxol-induced growth arrest. J. Biol. Chem., 1998, 273(46), 30777-30784.
[http://dx.doi.org/10.1074/jbc.273.46.30777] [PMID: 9804855]
[46]
Bratton, S.B.; Salvesen, G.S. Regulation of the Apaf-1-caspase-9 apoptosome. J. Cell Sci., 2010, 123(Pt 19), 3209-3214.
[http://dx.doi.org/10.1242/jcs.073643] [PMID: 20844150]
[47]
Haschka, M.D.; Soratroi, C.; Kirschnek, S.; Häcker, G.; Hilbe, R.; Geley, S.; Villunger, A.; Fava, L.L. The NOXA-MCL1-BIM axis defines lifespan on extended mitotic arrest. Nat. Commun., 2015, 6(1), 6891.
[http://dx.doi.org/10.1038/ncomms7891] [PMID: 25922916]
[48]
Jackson, R.S., II; Placzek, W.; Fernandez, A.; Ziaee, S.; Chu, C.Y.; Wei, J.; Stebbins, J.; Kitada, S.; Fritz, G.; Reed, J.C.; Chung, L.W.; Pellecchia, M.; Bhowmick, N.A. Sabutoclax, a Mcl-1 antagonist, inhibits tumorigenesis in transgenic mouse and human xenograft models of prostate cancer. Neoplasia, 2012, 14(7), 656-665.
[http://dx.doi.org/10.1593/neo.12640] [PMID: 22904682]
[49]
Cui, J.; Placzek, W.J. PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeutics. Cell Death Differ., 2016, 23(10), 1681-1690.
[http://dx.doi.org/10.1038/cdd.2016.60] [PMID: 27367564]
[50]
Liu, P.; Qin, Y.; Wu, L.; Yang, S.; Li, N.; Wang, H.; Xu, H.; Sun, K.; Zhang, S.; Han, X.; Sun, Y.; Shi, Y. A phase I clinical trial assessing the safety and tolerability of combretastatin A4 phosphate injections. Anticancer Drugs, 2014, 25(4), 462-471.
[http://dx.doi.org/10.1097/CAD.0000000000000070] [PMID: 24500030]
[51]
Nathan, P.; Zweifel, M.; Padhani, A.R.; Koh, D.M.; Ng, M.; Collins, D.J.; Harris, A.; Carden, C.; Smythe, J.; Fisher, N.; Taylor, N.J.; Stir-ling, J.J.; Lu, S.P.; Leach, M.O.; Rustin, G.J.; Judson, I. Phase I trial of combretastatin A4 phosphate (CA4P) in combination with bevaci-zumab in patients with advanced cancer. Clin. Cancer Res., 2012, 18(12), 3428-3439.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-3376] [PMID: 22645052]
[52]
Cogle, C.R.; Collins, B.; Turner, D.; Pettiford, L.C.; Bossé, R.; Hawkins, K.E.; Beachamp, Z.; Wise, E.; Cline, C.; May, W.S.; Moreb, J.S.; Hsu, J.; Hiemenz, J.; Brown, R.; Norkin, M.; Wingard, J.R.; Uckun, F. Safety, feasibility and preliminary efficacy of single agent com-bretastatin A1 diphosphate (OXi4503) in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes. Br. J. Haematol., 2020, 189(5), e211-e213.
[http://dx.doi.org/10.1111/bjh.16629] [PMID: 32236943]