Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Letter Article

Effect of Hybrid Compounds of Stilbene and Pentadienone on Inhibition of Tubulin Polymerization

Author(s): Jihyun Park, Dongsoo Koh, Young Han Lee, Yoongho Lim and Soon Young Shin*

Volume 23, Issue 10, 2023

Published on: 15 March, 2023

Page: [1156 - 1163] Pages: 8

DOI: 10.2174/1871520623666230216091116

Price: $65

Abstract

Introduction: Tubulin polymerization inhibitors induce cancer cell death; therefore, they can be developed as chemotherapeutic agents. We hypothesized that hybrid compounds, including the trans-stilbene moiety contained in resveratrol and penta-1,4-dien-3-one contained in curcumin, could inhibit tubulin polymerization.

Methods: Twenty-six hybrid stilbene and pentadienone compounds were designed and synthesized. The cytotoxicity of the hybrid compounds against MDA-MB-231 human breast cancer cells was determined using a clonogenic long-term survival assay. The relationship between cytotoxicity and structural properties was evaluated. Biological activities, including inhibition of tubulin polymerization and cell cycle progression, were investigated to select compounds with excellent anticancer properties. The molecular binding mode between the selected compound and the α, β-tubulin dimers was investigated.

Results: Twenty-six hybrid stilbene and pentadienone compounds were designed and synthesized. Among them, compound 13 exhibited the highest inhibitory effect on the clonogenicity of MDA-MB-231 cells. Compound 13 induced the destabilization of tubulins and inhibited cell cycle progression at the G2/M phase. Through in silico molecular docking analysis, compound 13 was predicted to bind to the colchicine binding site of α, β-tubulin.

Conclusion: The stilbene and pentadienone hybrid compound 13 has a binding mode similar to that of colchicine. Compound 13 inhibited the clonogenicity of MDA-MB-231 cells through a mechanism that destabilizes tubulin polymerization, leading to cell cycle arrest at the G2/M phase.

« Previous Next »
Graphical Abstract

[1]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin., 2022, 72(1), 7-33.
[http://dx.doi.org/10.3322/caac.21708] [PMID: 35020204]
[2]
Nunnery, S.E.; Mayer, I.A.; Balko, J.M. Triple-negative breast cancer: breast tumors with an identity crisis. Cancer J., 2021, 27(1), 2-7.
[http://dx.doi.org/10.1097/PPO.0000000000000494] [PMID: 33475287]
[3]
Cleator, S.; Heller, W.; Coombes, R.C. Triple-negative breast cancer: Therapeutic options. Lancet Oncol., 2007, 8(3), 235-244.
[http://dx.doi.org/10.1016/S1470-2045(07)70074-8] [PMID: 17329194]
[4]
Silva, P.; Barbosa, J.; Nascimento, A.V.; Faria, J.; Reis, R.; Bousbaa, H. Monitoring the fidelity of mitotic chromosome segregation by the spindle assembly checkpoint. Cell Prolif., 2011, 44(5), 391-400.
[http://dx.doi.org/10.1111/j.1365-2184.2011.00767.x] [PMID: 21951282]
[5]
Nogales, E. Structural insights into microtubule function. Annu. Rev. Biochem., 2000, 69(1), 277-302.
[http://dx.doi.org/10.1146/annurev.biochem.69.1.277] [PMID: 10966460]
[6]
Bhalla, K.N. Microtubule-targeted anticancer agents and apoptosis. Oncogene, 2003, 22(56), 9075-9086.
[http://dx.doi.org/10.1038/sj.onc.1207233] [PMID: 14663486]
[7]
Peto, R.; Davies, C.; Godwin, J.; Gray, R.; Pan, H.C.; Clarke, M.; Cutter, D.; Darby, S.; McGale, P.; Taylor, C.; Wang, Y.C.; Bergh, J.; Di Leo, A.; Albain, K.; Swain, S.; Piccart, M.; Pritchard, K. Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100 000 women in 123 randomised trials. Lancet, 2012, 379(9814), 432-444.
[http://dx.doi.org/10.1016/S0140-6736(11)61625-5] [PMID: 22152853]
[8]
Lu, Y.; Chen, J.; Xiao, M.; Li, W.; Miller, D.D. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm. Res., 2012, 29(11), 2943-2971.
[http://dx.doi.org/10.1007/s11095-012-0828-z] [PMID: 22814904]
[9]
Moudi, M.; Go, R.; Yien, C.Y.S.; Nazre, M. Vinca alkaloids. Int. J. Prev. Med., 2013, 4(11), 1231-1235.
[PMID: 24404355]
[10]
Mikstacka, R.; Stefański, T.; Różański, J. Tubulin-interactive stilbene derivatives as anticancer agents. Cell. Mol. Biol. Lett., 2013, 18(3), 368-397.
[http://dx.doi.org/10.2478/s11658-013-0094-z] [PMID: 23818224]
[11]
Mikstacka, R.; Zielińska-Przyjemska, M.; Dutkiewicz, Z.; Cichocki, M.; Stefański, T.; Kaczmarek, M.; Baer-Dubowska, W. Cytotoxic, tubulin-interfering and proapoptotic activities of 4′-methylthio-trans-stilbene derivatives, analogues of trans-resveratrol. Cytotechnology, 2018, 70(5), 1349-1362.
[http://dx.doi.org/10.1007/s10616-018-0227-3] [PMID: 29808373]
[12]
Gupta, K.K.; Bharne, S.S.; Rathinasamy, K.; Naik, N.R.; Panda, D. Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding. FEBS J., 2006, 273(23), 5320-5332.
[http://dx.doi.org/10.1111/j.1742-4658.2006.05525.x] [PMID: 17069615]
[13]
Paidakula, S.; Nerella, S.; Kankala, S.; Kankala, R.K. Recent trends in tubulin-binding combretastatin A-4 analogs for anticancer drug development. Curr. Med. Chem., 2022, 29(21), 3748-3773.
[http://dx.doi.org/10.2174/0929867328666211202101641] [PMID: 34856892]
[14]
Park, J.; Ahn, S.; Lee, Y.; Koh, D.; Lim, Y. 1 H and 13 C NMR spectral assignments of twenty-six 1-aryl-5-(2-(styryl)phenyl)penta-1,4-dien-3-ones. Magn. Reson. Chem., 2020, 58(4), 334-346.
[http://dx.doi.org/10.1002/mrc.4993] [PMID: 31953938]
[15]
Franken, N.A.P.; Rodermond, H.M.; Stap, J.; Haveman, J.; van Bree, C. Clonogenic assay of cells in vitro. Nat. Protoc., 2006, 1(5), 2315-2319.
[http://dx.doi.org/10.1038/nprot.2006.339] [PMID: 17406473]
[16]
Króliczewski, J.; Bartoszewska, S.; Dudkowska, M.; Janiszewska, D.; Biernatowska, A.; Crossman, D.K.; Krzymiński, K.; Wysocka, M.; Romanowska, A.; Baginski, M.; Markuszewski, M.; Ochocka, R.J.; Collawn, J.F.; Sikorski, A.F.; Sikora, E.; Bartoszewski, R. Utilizing genome-wide mRNA profiling to identify the cytotoxic chemotherapeutic mechanism of triazoloacridone C-1305 as direct microtubule stabilization. Cancers, 2020, 12(4), 864.
[http://dx.doi.org/10.3390/cancers12040864] [PMID: 32252403]
[17]
Lee, Y.H.; Park, J.; Ahn, S.; Lee, Y.; Lee, J.; Shin, S.Y.; Koh, D.; Lim, Y. Design, synthesis, and biological evaluation of polyphenols with 4,6-diphenylpyrimidin-2-amine derivatives for inhibition of Aurora kinase A. Daru, 2019, 27(1), 265-281.
[http://dx.doi.org/10.1007/s40199-019-00272-5] [PMID: 31154600]
[18]
Jung, H.; Ahn, S.; Kim, B.S.; Shin, S.Y.; Lee, Y.H.; Lim, Y. Isoflavones as modulators of adenosine monophosphate-activated protein kinase. Appl. Biol. Chem., 2016, 59(2), 217-225.
[http://dx.doi.org/10.1007/s13765-016-0149-8]
[19]
Kim, B.S.; Shin, S.Y.; Ahn, S.; Koh, D.; Lee, Y.H.; Lim, Y. Biological evaluation of 2-pyrazolinyl-1-carbothioamide derivatives against HCT116 human colorectal cancer cell lines and elucidation on QSAR and molecular binding modes. Bioorg. Med. Chem., 2017, 25(20), 5423-5432.
[http://dx.doi.org/10.1016/j.bmc.2017.07.062] [PMID: 28811071]
[20]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[21]
Gigant, B.; Wang, C.; Ravelli, R.B.G.; Roussi, F.; Steinmetz, M.O.; Curmi, P.A.; Sobel, A.; Knossow, M. Structural basis for the regulation of tubulin by vinblastine. Nature, 2005, 435(7041), 519-522.
[http://dx.doi.org/10.1038/nature03566] [PMID: 15917812]
[22]
Kramer, B.; Rarey, M.; Lengauer, T. Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking. Proteins, 1999, 37(2), 228-241.
[http://dx.doi.org/10.1002/(SICI)1097-0134(19991101)37:2<228:AID-PROT8>3.0.CO;2-8] [PMID: 10584068]
[23]
Song, Y.W.; Lim, Y.; Cho, S.K. 2,4-Di-tert-butylphenol, a potential HDAC6 inhibitor, induces senescence and mitotic catastrophe in human gastric adenocarcinoma AGS cells. Biochim. Biophys. Acta Mol. Cell Res., 2018, 1865(5), 675-683.
[http://dx.doi.org/10.1016/j.bbamcr.2018.02.003] [PMID: 29427610]
[24]
Shin, S.Y.; Jung, E.; Yeo, H.; Ahn, S.; Lee, Y.; Park, J.; Kang, H.; Yeo, W.S.; Koh, D.; Lim, Y. Design, synthesis, and biological activities of 3-((4,6-diphenylpyrimidin-2-ylamino)methylene)-2,3-dihydrochromen-4-ones. Bioorg. Chem., 2022, 120105634
[http://dx.doi.org/10.1016/j.bioorg.2022.105634] [PMID: 35114524]
[25]
He, W.; Zhang, M.G.; Wang, X.J.; Zhong, S.; Shao, Y.; Zhu, Y.; Shen, Z.J. AURKA suppression induces DU145 apoptosis and sensitizes DU145 to docetaxel treatment. Am. J. Transl. Res., 2013, 5(3), 359-367.
[PMID: 23634246]
[26]
Matthews, H.K.; Bertoli, C.; de Bruin, R.A.M. Cell cycle control in cancer. Nat. Rev. Mol. Cell Biol., 2022, 23(1), 74-88.
[http://dx.doi.org/10.1038/s41580-021-00404-3] [PMID: 34508254]
[27]
Mollinedo, F.; Gajate, C. Microtubules, microtubule-interfering agents and apoptosis. Apoptosis, 2003, 8(5), 413-450.
[http://dx.doi.org/10.1023/A:1025513106330] [PMID: 12975575]
[28]
Shin, S.Y.; Kim, J.H.; Yoon, H.; Choi, Y.K.; Koh, D.; Lim, Y.; Lee, Y.H. Novel antimitotic activity of 2-hydroxy-4-methoxy-2′,3′-benzochalcone (HymnPro) through the inhibition of tubulin polymerization. J. Agric. Food Chem., 2013, 61(51), 12588-12597.
[http://dx.doi.org/10.1021/jf4034688] [PMID: 24308485]
[29]
Wu, R.; Ding, W.; Liu, T.; Zhu, H.; Hu, Y.; Yang, B.; He, Q. XN05, a novel synthesized microtubule inhibitor, exhibits potent activity against human carcinoma cells in vitro. Cancer Lett., 2009, 285(1), 13-22.
[http://dx.doi.org/10.1016/j.canlet.2009.04.042] [PMID: 19647933]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy