Design of new disubstituted imidazo[1,2-b]pyridazine derivatives as selective Haspin inhibitors. Synthesis, binding mode and anticancer biological evaluation

References

• Wilson L, Jordan MA. New microtubule/tubulin-targeted anticancer drugs and novel chemotherapeutic strategies. J Chemother 2004;16: 83–5.
   PubMed Web of Science ®Google Scholar
• Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nat Rev Cancer 2004;4:927–36.
   PubMed Web of Science ®Google Scholar
• de Carcer G, Perez de Castro I, Malumbres M. Targeting cell cycle kinases for cancer therapy. Curr Med Chem 2007;14:969–85.
   PubMed Web of Science ®Google Scholar
• Schmidt M, Bastians H. Mitotic drug targets and the development of novel anti-mitotic anticancer drugs. Drug Resist Updat 2007;10:162–81.
   PubMed Web of Science ®Google Scholar
• Mountzios G, Terpos E, Dimopoulos MA. Aurora kinases as targets for cancer therapy. Cancer Treat Rev 2008;34:175–82.
   PubMed Web of Science ®Google Scholar
• Ruchaud S, Carmena M, Earnshaw WC. Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 2007;8:798–812.
   PubMed Web of Science ®Google Scholar
• Vader G, Lens SM. The Aurora kinase family in cell division and cancer. Biochim Biophys Acta 2008;1786:60–72.
   PubMed Web of Science ®Google Scholar
• Cheung CH, Sarvagalla S, Lee JY, et al. Aurora kinase inhibitor patents and agents in clinical testing: an update (2011–2013). Expert Opin Ther Pat 2014;24:1021–38.
   PubMed Web of Science ®Google Scholar
• Guo J, Anderson MG, Tapang P, et al. Identification of genes that confer tumor cell resistance to the aurora B kinase inhibitor, AZD1152. Pharmacogenomics J 2009;9:90–102.
   PubMed Web of Science ®Google Scholar
• Jelluma N, Brenkman AB, van den Broek NJ, et al. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell 2008;132:233–46.
   PubMed Web of Science ®Google Scholar
• Petsalaki E, Akoumianaki T, Black EJ, et al. Phosphorylation at serine 331 is required for Aurora B activation. J Cell Biol 2011;195:449–66.
   PubMed Web of Science ®Google Scholar
• Petsalaki E, Zachos G. Clks 1, 2 and 4 prevent chromatin breakage by regulating the Aurora B-dependent abscission checkpoint. Nat Commun 2016;7:11451.
   PubMed Web of Science ®Google Scholar
• De Antoni A, Maffini S, Knapp S, et al. A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B. J Cell Biol 2012;199:269–84.
   PubMed Web of Science ®Google Scholar
• Dai J, Higgins JM. Haspin: a mitotic histone kinase required for metaphase chromosome alignment. Cell Cycle 2005;4:665–8.
   PubMed Web of Science ®Google Scholar
• Dai J, Sultan S, Taylor SS, Higgins JM. The kinase Haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes Dev 2005;19:472–88.
   PubMed Web of Science ®Google Scholar
• Wang F, Ulyanova NP, van der Waal MS, et al. A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. Curr Biol 2011;21:1061–9.
   PubMed Web of Science ®Google Scholar
• Wang F, Ulyanova NP, Daum JR, et al. Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. J Cell Biol 2012;199:251–68.
   PubMed Web of Science ®Google Scholar
• Dai J, Sullivan BA, Higgins JM. Regulation of mitotic chromosome cohesion by Haspin and Aurora B. Dev Cell 2006;11:741–50.
   PubMed Web of Science ®Google Scholar
• Dai J, Kateneva AV, Higgins JM. Studies of Haspin-depleted cells reveal that spindle-pole integrity in mitosis requires chromosome cohesion. J Cell Sci 2009;122:4168–76.
   PubMed Web of Science ®Google Scholar
• Liang C, Chen Q, Yi Q, et al. A kinase-dependent role for Haspin in antagonizing Wapl and protecting mitotic centromere cohesion. EMBO Rep 2018;19:43–56.
   PubMed Web of Science ®Google Scholar
• Kelly AE, Ghenoiu C, Xue JZ, et al. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science 2010;330:235–9.
   PubMed Web of Science ®Google Scholar
• Wang F, Dai J, Daum JR, et al. Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 2010;330:231–5.
   PubMed Web of Science ®Google Scholar
• Yamagishi Y, Honda T, Tanno Y, Watanabe Y. Two histone marks establish the inner centromere and chromosome bi-orientation. Science 2010;330:239–43.
   PubMed Web of Science ®Google Scholar
• Huertas D, Soler M, Moreto J, et al. Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin. Oncogene 2012;31:1408–18.
   PubMed Web of Science ®Google Scholar
• McKinley KL, Cheeseman IM. Large-scale analysis of CRISPR/Cas9 cell-cycle knockouts reveals the diversity of p53-dependent responses to cell-cycle defects. Dev Cell 2017;40:405–20.e2.
   PubMed Web of Science ®Google Scholar
• Dave SS, Fu K, Wright GW, et al. Molecular diagnosis of Burkitt’s lymphoma. N Engl J Med 2006;354:2431–42.
   PubMed Web of Science ®Google Scholar
• Rosenwald A, Alizadeh AA, Widhopf G, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001;194:1639–47.
   PubMed Web of Science ®Google Scholar
• Han X, Kuang T, Ren Y, et al. Haspin knockdown can inhibit progression and development of pancreatic cancer in vitro and vivo. Exp Cell Res 2019;385:111605.
   PubMed Web of Science ®Google Scholar
• Bastea LI, Hollant LMA, Doppler HR, et al. Sangivamycin and its derivatives inhibit Haspin-Histone H3-survivin signaling and induce pancreatic cancer cell death. Sci Rep 2019;9:16588.
   PubMed Web of Science ®Google Scholar
• Eswaran J, Patnaik D, Filippakopoulos P, et al. Structure and functional characterization of the atypical human kinase Haspin. Proc Natl Acad Sci U S A 2009;106:20198–203.
   PubMed Web of Science ®Google Scholar
• Villa F, Capasso P, Tortorici M, et al. Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization. Proc Natl Acad Sci U S A 2009;106:20204–9.
   PubMed Web of Science ®Google Scholar
• Chen LS, Redkar S, Bearss D, et al. Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood 2009;114:4150–7.
   PubMed Web of Science ®Google Scholar
• Patnaik D, Jun X, Glicksman MA, et al. Identification of small molecule inhibitors of the mitotic kinase Haspin by high-throughput screening using a homogeneous time-resolved fluorescence resonance energy transfer assay. J Biomol Screen 2008;13:1025–34.
   PubMedGoogle Scholar
• Cuny GD, Robin M, Ulyanova NP, et al. Structure-activity relationship study of acridine analogs as Haspin and DYRK2 kinase inhibitors. Bioorg Med Chem Lett 2010;20:3491–4.
   PubMed Web of Science ®Google Scholar
• Opoku-Temeng C, Dayal N, Aflaki Sooreshjani M, Sintim HO. 3H-pyrazolo[4,3-f]quinoline Haspin kinase inhibitors and anticancer properties. Bioorg Chem 2018;78:418–26.
   PubMed Web of Science ®Google Scholar
• Kim JE, Lee SY, Jang M, et al. Coumestrol epigenetically suppresses cancer cell proliferation: coumestrol is a natural Haspin kinase inhibitor. Int J Mol Sci 2017;18:2228.
   Web of Science ®Google Scholar
• Han L, Wang P, Sun Y, et al. Anti-melanoma activities of Haspin inhibitor CHR-6494 deployed as a single agent or in a synergistic combination with MEK inhibitor. J Cancer 2017;8:2933–43.
   PubMed Web of Science ®Google Scholar
• Bendjeddou LZ, Loaec N, Villiers B, et al. Exploration of the imidazo[1,2-b]pyridazine scaffold as a protein kinase inhibitor. Eur J Med Chem 2017;125:696–709.
   PubMed Web of Science ®Google Scholar
• Belaroussi R, El Hakmaoui A, Akssira M, et al. Regioselective synthesis of 2,4‐substituted pyrido[1′,2′:1,5]pyrazolo[3,4‐d]pyrimidines through sequential Pd‐catalyzed arylation and SNAr reactions. Eur J Org Chem 2016; 2016:3550–8.
   Web of Science ®Google Scholar
• Copin C, Henry N, Buron F, Routier S. Palladium-catalyzed direct arylation of 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles. Synlett 2016;27:1091–5.
   Web of Science ®Google Scholar
• Belaroussi REH, Percina A, Chartier N, et al. Synthesis of 1,4-disubstituted pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyridazines by means of SNAr and palladium-catalysed reactions. Eur J Org Chem 2015;2015:4006–17.
   Web of Science ®Google Scholar
• Modi V, Dunbrack RL Jr. Defining a new nomenclature for the structures of active and inactive kinases. Proc Natl Acad Sci U S A 2019;116:6818–27.
   PubMed Web of Science ®Google Scholar
• Chaikuad A, Diharce J, Schröder M, et al. An unusual binding model of the methyl 9-anilinothiazolo[5,4-f] quinazoline-2-carbimidates (EHT 1610 and EHT 5372) confers high selectivity for dual-specificity tyrosine phosphorylation-regulated kinases. J Med Chem 2016;59:10315–21.
   PubMed Web of Science ®Google Scholar
• Edmondson R, Broglie JJ, Adcock AF, Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol 2014;12:207–18.
   PubMed Web of Science ®Google Scholar
• Nigg EA. Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. Bioessays 1995;17:471–80.
   PubMed Web of Science ®Google Scholar
• Hochegger H, Takeda S, Hunt T. Cyclin-dependent kinases and cell-cycle transitions: does one fit all?. Nat Rev Mol Cell Biol 2008;9:910–6.
   PubMed Web of Science ®Google Scholar
• Sherr CJ. Growth factor-regulated G1 cyclins. Stem Cells 1994;12: 47–55. discussion 55–47.
   PubMed Web of Science ®Google Scholar
• Meyerson M, Harlow E. Identification of G1 kinase activity for cdk6, a novel cyclin D partner. Mol Cell Biol 1994;14:2077–86.
   PubMed Web of Science ®Google Scholar
• Feizbakhsh O, Pontheaux F, Glippa V, et al. A Peak of H3T3 Phosphorylation Occurs in Synchrony with Mitosis in Sea Urchin Early Embryos. Cells 2020;9:898.
   Web of Science ®Google Scholar
• Parrilla A, Cirillo L, Thomas Y, et al. Mitotic entry: the interplay between Cdk1, Plk1 and Bora. Cell Cycle 2016;15:3177–82.
   PubMed Web of Science ®Google Scholar
• Carles F, Bourg S, Meyer C, Bonnet P. PKIDB: a curated, annotated and updated database of protein kinase inhibitors in clinical trials. Molecules 2018; 23:908.
   Web of Science ®Google Scholar