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Research Paper

Synthesis and preliminary structure-activity relationship study of 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors

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Pages 171-183 | Received 21 Sep 2017, Accepted 08 Nov 2017, Published online: 06 Dec 2017

References

  • Mekheimer RA, Ahmed EA, Sadek KU. Recent developments in the chemistry of pyrazolo[4,3-c]quinolines. Tetrahedron 2012;68:1637–67.
  • Savini L, Massarelli P, Nencini C, et al. High affinity central benzodiazepine receptor ligands: Synthesis and structure-activity relationship studies of a new series of pyrazolo[4,3-c]quinolin-3-ones. Bioorg Med Chem 1998;6:389–99.
  • Savini L, Chiasserini L, Pellerano C, et al. High affinity central benzodiazepine receptor ligands. Part 2: quantitative structure-activity relationships and comparative molecular analysis of pyrazolo[4,3-c]quinolin-3-ones. Bioorg Med Chem 2001;9:431–44.
  • Carotti A, Altomare C, Savini L, et al. High affinity central benzodiazepine receptor ligands. Part 3: insights into the pharmacophore and pattern recognition study of intrinsic activities of pyrazolo[4,3-c]quinolin-3-ones. Bioorg Med Chem 2003;11:5259–72.
  • Baruah B, Dasu K, Vaitilingam B, et al. 2-Diaryl-1-ethanone and pyrazolo[4,3-c] quinoline-4-one as novel selective cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett 2004;14:445–8.
  • Crespo MI, Gràcia J, Puig C, et al. Synthesis and biological evaluation of 2,5-dihydropyrazolo[4,3-c]quinolin-3-ones, a novel series of PDE 4 inhibitors with low emetic potential and antiasthmatic properties. Bioorg Med Chem Lett 2000;10:2661–4.
  • Wentland MP, Preparation of 5-cyclopropyl-8-fluoro-7-(4-pyridyl-3H-pyrazolo[4,3-c]quinolin-3-one topoisomerase-inhibiting anticancer agents. New York; US Patent 5334595, 1994.
  • Wentland MP, Aldous SC, Gruett MD, et al. The antitumor activity of novel pyrazoloquinoline derivatives. Bioorg Med Chem Lett 1995;5:405–10.
  • Brnardic EJ, Garbaccio RM, Fraley ME, et al. Optimization of a pyrazoloquinolinone class of Chk1 kinase inhibitors. Bioorg Med Chem Lett 2007;17:5989–94.
  • Oza V, Ashwell S, Brassil P, et al. Discovery of a novel class of triazolones as checkpoint kinase inhibitors-hit to lead exploration. Bioorg Med Chem Lett 2010;20:5133–8.
  • Oza V, Ashwell S, Brassil P, et al. Synthesis and evaluation of triazolones as checkpoint kinase 1 inhibitors. Bioorg Med Chem Lett 2012;22:2330–7.
  • Sanchez Y, Wong C, Thoma RS, et al. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 1997;277:1497–501.
  • Bartek J, Lukas J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 2003;3:421–9.
  • Bryant C, Rawlinson R, Massey AJ. Chk1 inhibition as a novel therapeutic strategy for treating triple-negative breast and ovarian cancers. BMC Cancer 2014;14:1.
  • Ashwell S, Zabludoff S. DNA damage detection and repair pathways-recent advances with inhibitors of checkpoint kinases in cancer therapy. Clin Cancer Res 2008;14:4032–7.
  • Wang Q, Fan S, Eastman A, et al. UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst 1996;88:956–65.
  • Zhao B, Bower MJ, McDevitt PJ, et al. Structural basis for Chk1 inhibition by UCN-01. J Biol Chem 2002;277:46609–15.
  • Zabludoff SD, Deng C, Grondine MR, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther 2008;7:2955–66.
  • Ashwell S, Janetka JW, Zabludoff S. Keeping checkpoint kinases in line: new selective inhibitors in clinical trials. Expert Opin Investig Drugs 2008;17:1331–40.
  • Daud A, Springett GM, Mendelson DS, et al. A phase I dose-escalation study of SCH 900776, a selective inhibitor of checkpoint kinase 1 (CHK1), in combination with gemcitabine (Gem) in subjects with advanced solid tumors. J Clin Oncol 2010;28:suppl; abstr 3064).
  • Daud AI, Ashworth MT, Strosberg J, et al. Phase I dose-escalation trial of checkpoint kinase 1 inhibitor MK-8776 as monotherapy and in combination with gemcitabine in patients with advanced solid tumors. J Clin Oncol 2015;33:1060–6.
  • Sakurikar N, Eastman A. Will targeting Chk1 have a role in the future of cancer therapy? J Clin Oncol 2015;33:1075–7.
  • Yokoyama N, Ritter B, Neubert AD. 2-Arylpyrazolo[4,3-c]quinolin-3-ones: novel agonist, partial agonist, and antagonist of benzodiazepines. J Med Chem 1982;25:337–9.
  • De Oliveira MRP, Alves TR, Pinto AC, et al. Synthesis and antiviral activities of new pyrazolo[4,3‐c]quinolin‐3‐ones and their ribonucleoside derivatives. Nucleosides Nucleotides Nucleic Acids 2004;23:735–48.
  • Karolak-Wojciechowska J, Lange J, Książek W, et al. Structure–activity relationship investigations of the modulating effect of core substituents on the affinity of pyrazoloquinolinone congeners for the benzodiazepine receptor. Il Farm 1998;53:579–85.
  • Zhang P, Zhang W, Liu R, et al. Synthesis of novel imidazobenzodiazepines as probes of the pharmacophore for “diazepam-insensitive” GABAA receptors. J Med Chem 1995;38:1679–88.
  • López Rivilli MJ, Moyano EL, Yranzo GI. An alternative approach toward 2-aryl-2H-pyrazolo[4,3-c]-quinolin-3-ones by a multistep synthesis. Tetrahedron Lett 2010;51:478–81.
  • GOLD suite, version 5.2; Cambridge Crystallographic Data Centre: Cambridge, UK. Available from: https://www.ccdc.cam.ac.uk [last accessed 21 Jun 2017].
  • Case DA, Babin V, Berryman J, et al. AMBER14. University of California, San Francisco; 2014. Available from: http://ambermd.org [last accessed 4 Aug 2017].
  • Wang J, Wolf RM, Caldwell JW, et al. Development and testing of a general amber force field. J Comput Chem 2004;25:1157–74.
  • Molecular Operating Environment (MOE), 2014.09. Chemical Computing Group Inc.: Canada. Available from: https://www.chemcomp.com/MOE-Molecular_Operating_Environment.htm [last accessed 29 Jul 2017].
  • Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph 1996;14:33–8.
  • Stavenger RA, Zhao B, Zhou B-BS, et al. Pyrrolo[2,3-b]pyridines inhibit the checkpoint kinase Chk1. Available from: http://www.rcsb.org/pdb/explore/explore.do?structureId=1zys [last accessed 22 May 2017].
  • Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res 2000;28:235–42.
  • Labute P. Protonate3D: Assignment of ionization states and hydrogen coordinates to macromolecular structures. Proteins 2009;75:187–205.
  • Halgren TA. Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data, and empirical rules. J Comput Chem 1996;17:616–41.
  • Stewart JJP. Optimization of parameters for semiempirical methods I. Method. J Comput Chem 1989;10:209–20.
  • Stewart JJP. Optimization of parameters for semiempirical methods II. Applications. J Comput Chem 1989;10:221–64.
  • Stewart JJP. MOPAC2012 (version 2012). Available from: http://OpenMOPAC.net [last accessed 29 Jul 2017].
  • Stewart JJP. Optimization of parameters for semiempirical methods V: Modification of NDDO approximations and application to 70 elements. J Mol Model 2007;13:1173–213.
  • Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 09, Revision B.01. Wallingford (CT): Gaussian, Inc.; 2010. Available from: gaussian.com [last accessed 21 Jul 2017].
  • Hornak V, Abel R, Okur A, et al. Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins 2006;65:712–25.
  • Jorgensen WL, Chandrasekhar J, Madura JD, et al. Comparison of simple potential functions for simulating liquid water. J Chem Phys 1983;79:926–35.
  • Berendsen HJC, Postma JPM, van Gunsteren WF, et al. Molecular dynamics with coupling to an external bath. J Chem Phys 1984;81:3684–90.
  • Loncharich RJ, Brooks BR, Pastor RW. Langevin dynamics of peptides: the frictional dependence of isomerization rates of N-acetylalanyl-N'-methylamide. Biopolymers 1992;32:523–35.
  • Kräutler V, van Gunsteren WF, Hünenberger PH. A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations. J Comput Chem 2001;22:501–8.
  • Essmann U, Perera L, Berkowitz ML, et al. A smooth particle mesh Ewald method. J Chem Phys 1995;103:8577–93.
  • Cuzzolin A, Sturlese M, Deganutti G, et al. Deciphering the complexity of ligand–protein recognition pathways using supervised molecular dynamics (SuMD) simulations. J Chem Inf Model 2016;56:687–705.
  • Malvacio I, Vera DMA, Moyano EL. Microwave assisted synthesis of ethyl-quinolon-4-one-3-carboxylates and hydrolysis to quinolon-4-one-3-carboxylic Acids. Curr Microw Chem 2014;1:52–8.
  • Huang S, Garbaccio RM, Fraley ME, et al. Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors. Bioorg Med Chem Lett 2006;16:5907–12.
  • RCSB Protein Data Bank. Available from: http://www.rcsb.org/pdb/home/home.do [last accessed 22 May 2017].
  • Cuzzolin A, Sturlese M, Malvacio I, et al. DockBench: an integrated informatic platform bridging the gap between the robust validation of docking protocols and virtual screening simulations. Molecules 2015;20:9977–93.
  • Ferreira VF, Leal KZ, Lindgren EB, et al. Structural evaluation of three 2-phenylpyrazolo[4,3-c]quinolin-3-one monohydrates. J Mol Struct 2013;1051:299–309.
  • Foloppe N, Fisher LM, Howes R, et al. Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein − ligand affinity. J Med Chem 2005;48:4332–45.
  • Tao Z-F, Wang L, Stewart KD, et al. Structure-based design, synthesis, and biological evaluation of potent and selective macrocyclic checkpoint kinase 1 inhibitors. J Med Chem 2007;50:1514–27.
  • Ambre PK, Pissurlenkar RRS, Coutinho EC, Iyer RP. Identification of new checkpoint kinase-1 (Chk1) inhibitors by docking, 3D-QSAR, and pharmacophore-modeling methods. Can J Chem 2012;90:675–92.
  • Lv M, Ma S, Tian Y, et al. Computational studies on the binding mechanism between triazolone inhibitors and Chk1 by molecular docking and molecular dynamics. Mol Biosyst 2015;11:275–86.
  • Kumar V, Khan S, Gupta P, et al. Identification of novel inhibitors of human Chk1 using pharmacophore-based virtual screening and their evaluation as potential anti-cancer agents. J Comput Aided Mol Des 2014;28:1247–56.