Design, synthesis, in vitro antiproliferative activity and apoptosis-inducing studies of 1-(3′,4′,5′-trimethoxyphenyl)-3-(2′-alkoxycarbonylindolyl)-2-propen-1-one derivatives obtained by a molecular hybridisation approach

References

• Janke C. The tubulin code: molecular components, readout mechanisms, and functions. J Cell Biol 2014;206:461–72.
   PubMed Web of Science ®Google Scholar
• Akhmanova A, Steinmetz MO. Control of microtubule organization and dynamics: two ends in the limelight. Nat Rev Mol Cell Biol 2015;16:711–26.
   PubMed Web of Science ®Google Scholar
• Sorger PK, Dobles M, Tournebize R, Hyman AA. Coupling cell division and cell death to microtubule dynamics. Curr Opin Cell Biol 1997;9:807–14.
   PubMed Web of Science ®Google Scholar
• Risinger AL, Giles FJ, Mooberry SL. Microtubule dynamics as a target in oncology. Cancer Treat Rev 2009;35:255–61.
   PubMed Web of Science ®Google Scholar
• Rohena CC, Mooberry SL. Recent progress with microtubule stabilizers: new compounds, binding modes and cellular activities. Nat Prod Rep 2014;31:335–55.
   PubMed Web of Science ®Google Scholar
• Vindya NG, Sharma N, Yadav M, Ethiraj KR. Tubulins - the target for anticancer therapy. Curr Top Med Chem 2015;15:73–82.
   PubMed Web of Science ®Google Scholar
• Nitika V, Kapil K. Microtubule targeting agents: a benchmark in cancer therapy. Curr Drug Ther 2014;8:189–96.
   Google Scholar
• Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer 2004;100:2491–9.
   PubMed Web of Science ®Google Scholar
• Perez-Perez MJ, Priego EM, Bueno O, et al. Blocking blood flow to solid tumors by destabilizing tubulin: an approach to targeting tumor growth. J Med Chem 2016;59:8685–711.
   PubMed Web of Science ®Google Scholar
• van Vuuren RJ, Visagie MH, Theron AE, Joubert AM. Antimitotic drugs in the treatment of cancer. Cancer Chemother Pharmacol 2015;76:1101–12.
   PubMed Web of Science ®Google Scholar
• Mukhtar E, Adhami VM, Mukhtar H. Targeting microtubules by natural agents for cancer therapy. Mol Cancer Ther 2014;13:275–84.
   PubMed Web of Science ®Google Scholar
• Seligmann J, Twelves C. Tubulin: an example of targeted chemotherapy. Future Med Chem 2013;5:339–52.
   PubMed Web of Science ®Google Scholar
• Liu YM, Chen HL, Lee HY, Liou JP. Tubulin inhibitors: a patent review. Expert Opin Ther Pat 2014;24:69–88.
   PubMed Web of Science ®Google Scholar
• Mahapatra DK, Bharti SK, Asati V. Anti-cancer chalcones: structural and molecular target perspectives. Eur J Med Chem 2015;98:69–114.
   PubMed Web of Science ®Google Scholar
• Zhuang C, Zhang W, Sheng C, et al. Chalcone: a privileged structure in medicinal chemistry. Chem Rev 2017;117:7762–810.
   PubMed Web of Science ®Google Scholar
• Karthikeyan C, Moorthy NS, Ramasamy S, et al. Advances in chalcones with anticancer activities. Recent Pat Anticancer Drug Discov 2015;10:97–115.
   PubMed Web of Science ®Google Scholar
• Ducki S, Forrest R, Hadfield JA, et al. Potent antimitotic and cell growth inhibitory properties of substituted chalcones. Bioorg Med Chem Lett 1998;8:1051–6.
   PubMed Web of Science ®Google Scholar
• Pettit GR, Singh SB, Hamel E, et al. Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia 1989;45:209–11.
   PubMedGoogle Scholar
• Brancale A, Silvestri R. Indole, a core nucleus for potent inhibitors of tubulin polymerization. Med Res Rev 2007;27:209–38.
   PubMed Web of Science ®Google Scholar
• Yan J, Chen J, Zhang S, et al. Synthesis, evaluation, and mechanism study of novel indole-chalcone derivatives exerting effective antitumor activity through microtubule destabilization in vitro and in vivo. J Med Chem 2016;59:5264–83.
   PubMed Web of Science ®Google Scholar
• Trabbic CJ, Overmeyer JH, Alexander EM, et al. Synthesis and biological evaluation of indolyl-pyridinyl-propenones having either methuosis or microtubule disruption activity. J Med Chem 2015;58:2489–512.
   PubMed Web of Science ®Google Scholar
• Trabbic CJ, George SM, Alexander EM, et al. Synthesis and biological evaluation of isomeric methoxy substitutions on anti-cancer indolyl-pyridinyl-propenones: effects on potency and mode of activity. Eur J Med Chem 2016;122:79–91.
   PubMed Web of Science ®Google Scholar
• Kumar D, Kumar NM, Akamatsu K, et al. Synthesis and biological evaluation of indolyl chalcones as antitumor agents. Bioorg Med Chem Lett 2010;20:3916–19.
   PubMed Web of Science ®Google Scholar
• De Martino G, La Regina G, Coluccia A, et al. Arylthioindoles, potent inhibitors of tubulin polymerization. J Med Chem 2004;47:6120–3.
   PubMed Web of Science ®Google Scholar
• De Martino G, Edler MC, La Regina G, et al. New arylthioindoles: potent inhibitors of tubulin polymerization. 2. Structure-activity relationships and molecular modeling studies. J Med Chem 2006;49:947–54.
   PubMed Web of Science ®Google Scholar
• La Regina G, Sarkar T, Bai R, 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.
   PubMed Web of Science ®Google Scholar
• For the characterization of compound 7a, see: Mistry SN, Shonberg J, Draper-Joyce CJ, et al. Discovery of a novel class of negative allosteric modulator of the dopamine D2 receptor through fragmentation of a bitopic ligand. J Med Chem 2015;58:6819–43.
   PubMed Web of Science ®Google Scholar
• For the characterization of compound 7b, see: Fugard AJ, Thompson BK, Slawin AMZ, et al. Organocatalytic synthesis of fused bicyclic 2,3-dihydro-1,3,4-oxadiazoles through an intramolecular cascade cyclization. Org Lett 2015;17:5824–7.
   PubMed Web of Science ®Google Scholar
• For the characterization of compound 7c and 7d, see reference 21.
   Google Scholar
• For the characterization of compound 7e, see: Coowar D, Bouissac J, Hanbali M, et al. Effects of indole fatty alcohols on the differentiation of neural stem cell derived neurospheres. J Med Chem 2004;47:6270–82.
   PubMed Web of Science ®Google Scholar
• For the characterization of compound 7f, see: Kim J, Jung YK, Kim C, et al. A novel series of highly potent small molecule inhibitors of rhinovirus replication. J Med Chem 2017;60:5472–92.
   PubMed Web of Science ®Google Scholar
• For the characterization of compound 8a and 9a, see: Bennasar M-L, Roca T, Ferrando F. Regioselective intramolecular reactions of 2-indolylacyl radicals with pyridines: a direct synthetic entry to Ellipticine Quinones. J Org Chem 2005;70:9077–80.
   PubMed Web of Science ®Google Scholar
• For the characterization of compound 8b and 8e, see: Chen H, Yang H, Wang Z, et al. Discovery of 3-substituted 1H-indole-2-carboxylic acid derivatives as a novel class of CysLT1 selective antagonists. ACS Med Chem Lett 2016;7:335–9.
   PubMed Web of Science ®Google Scholar
• For the characterization of compound 9b, see: Gokhale N, Panathur N, Dalimba U, et al. Novel indole-quinazolinone based amides as cytotoxic agents. J Heter Chem 2016;53:513–24.
   Web of Science ®Google Scholar
• For the characterization of compound 9i, see: Gueven A, Jones RA. Potentially tautomeric 1,2-dihydro-1-oxo-5H-pyridazino[4,5-b]indole and 3,4-dihydro-4-oxo-5H-pyridazino[4,5-b]indole. J Chem Res Synop 2010;24:no–3.
   Google Scholar
• Said M, Brouard I, Quintana J, Estévez F. Antiproliferative activity and apoptosis induction by 3',4'-dibenzyloxyflavonol on human leukemia cells. Chem Biol Interact 2017;268:13–23.
   PubMed Web of Science ®Google Scholar
• Rubio S, Quintana J, Eiroa JL, et al. Acetyl derivative of quercetin 3-methyl ether-induced cell death in human leukemia cells is amplified by the inhibition of ERK. Carcinogenesis 2007;28:2105–13.
   PubMed Web of Science ®Google Scholar
• Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.
   PubMed Web of Science ®Google Scholar
• De Lean A, Munson PJ, Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol 1978;235:E97–E102.
   PubMed Web of Science ®Google Scholar
• Hamel E. Evaluation of antimitotic agents by quantitative comparisons of their effects on the polymerization of purified tubulin. Cell Biochem Biophys 2003;38:1–21.
   PubMed Web of Science ®Google Scholar
• Verdier-Pinard P, Lai J-Y, Yoo H-D, et al. Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells. Mol Pharmacol 1998;53:62–7.
   PubMed Web of Science ®Google Scholar
• Estévez S, Marrero MT, Quintana J, Estévez F. Eupatorin-induced cell death in human leukemia cells is dependent on caspases and activates the mitogen-activated protein kinase pathway. PLoS One 2014;9:e112536.
   PubMed Web of Science ®Google Scholar
• Ebrahim AS, Sabbagh H, Liddane A, et al. Hematologic malignancies: newer strategies to counter the BCL-2 protein. J Cancer Res Clin Oncol 2016;142:2013–22.
   PubMed Web of Science ®Google Scholar
• Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 1997;275:1132–6.
   PubMed Web of Science ®Google Scholar
• Ling YH, Tornos C, Perez-Soler R. Phosphorylation of Bcl-2 is a marker of M phase events and not a determinant of apoptosis. J Biol Chem 1998;273:18984–91.
   PubMed Web of Science ®Google Scholar
• Scatena CD, Stewart ZA, Mays D, et al. Mitotic phosphorylation of Bcl-2 during normal cell cycle progression and taxol-induced growth arrest. J Biol Chem 1998;273:30777–84.
   PubMed Web of Science ®Google Scholar
• Yamamoto K, Ichijo H, Korsmeyer SJ. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 1999;19:8469–78.
   PubMed Web of Science ®Google Scholar
• Haschka MD, Soratroi C, Kirschnek S, et al. The NOXA-MCL1-BIM axis defines lifespan on extended mitotic arrest. Nat Commun 2015;6:6891
   PubMed Web of Science ®Google Scholar
• Eichhorn JM, Sakurikar N, Alford SE, et al. Critical role of anti-apoptotic Bcl-2 protein phosphorylation in mitotic death. Cell Death Dis 2013;4:e834.
   PubMed Web of Science ®Google Scholar
• Nishina H, Wada T, Katada T. Physiological roles of SAPK/JNK signaling pathway. J Biochem 2004;136:123–6.
   PubMed Web of Science ®Google Scholar