Exploring the transmission-blocking activity of antiplasmodial 3,6-diarylated imidazopyridazines

REFERENCES

• Adjalley, S.H., Johnston, G.L., Li, T., Eastman, R.T., Ekland, E.H., Eappen, A.G., Richman, A., Sim, B.K., Lee, M.C., Hoffman, S.L. & Fidock, D.A. 2011. Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue. Proceedings of the National Academy of Sciences of the United States of America 108: 1214–1223.
   PubMed Web of Science ®Google Scholar
• Alam, M.M., Solyakov, L., Bottrill, A.R., Flueck, C., Siddiqui, F.A., Singh, S., Mistry, S., Viskaduraki, M., Lee, K., Hopp, C.S., Chitnis, C.E., Doerig, C., Moon, R.W., Green, J.L., Holder, A.A., Baker, D.A. & Tobin, A.B. 2015. Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nature Communications 6: 7285.
   PubMed Web of Science ®Google Scholar
• Anamika, K., Srinivasan, N. & Krupa, A. 2005. A genomic perspective of protein kinases in Plasmodium falciparum. Proteins: Structure, Function, and Bioinformatics 58: 180–189.
   PubMed Web of Science ®Google Scholar
• Ansell, K.H., Jones, H.M., Whalley, D., Hearn, A., Taylor, D.L., Patin, E.C., Chapman, T.M., Osborne, S.A., Wallace, C., Birchall, K., Large, J., Bouloc, N., Smiljanic-Hurley, E., Clough, B., Moon, R.W., Green, J.L. & Holder, A.A. 2014. Biochemical and Antiparasitic Properties of Inhibitors of the Calcium-Dependent Protein Kinase PfCDPK1. Antimicrobial Agents and Chemotherapy 58: 6032–6043.
   PubMed Web of Science ®Google Scholar
• Birkholtz, L.-M., Coetzer, T.L., Mancama, D., Leroy, D. & Alano, P. 2016. Discovering New Transmission-Blocking Antimalarial Compounds: Challenges and Opportunities. Trends in Parasitology 32: 669–681.
   PubMed Web of Science ®Google Scholar
• Brochet, M., Collins, M.O., Smith, T.K., Thompson, E., Sebastian, S., Volkmann, K., Schwach, F., Chappell, L., Gomes, A.R., Berriman, M., Rayner, J.C., Baker, D.A., Choudhary, J. & Billker, O. 2014. Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca2+ signals at key decision points in the life cycle of malaria parasites. PLoS Biol 12: e1001806.
   PubMed Web of Science ®Google Scholar
• Brunschwig, C., Lawrence, N., Taylor, D., Abay, E., Njoroge, M., Basarab, G.S., Le Manach, C., Paquet, T., Cabrera, D.G., Nchinda, A.T., De Kock, C., Wiesner, L., Denti, P., Waterson, D., Blasco, B., Leroy, D., Witty, M.J., Donini, C., Duffy, J., Wittlin, S., White, K.L., Charman, S.A., Jiménez-Díaz, M.B., Angulo-Barturen, I., Herreros, E., Gamo, F.J., Rochford, R., Mancama, D., Coetzer, T.L., Van Der Watt, M.E., Reader, J., Birkholtz, L.M., Marsh, K.C., Solapure, S.M., Burke, J.E., Mcphail, J.A., Vanaerschot, M., Fidock, D.A., Fish, P.V., Siegl, P., Smith, D.A., Wirjanata, G., Noviyanti, R., Price, R.N., Marfurt, J., Silue, K.D., Street, L.J. & Chibale, K. 2018. UCT943, a Next-Generation Plasmodium falciparum PI4 K Inhibitor Preclinical Candidate for the Treatment of Malaria. Antimicrob Agents Chemother 62 (9): e00012–18.
   PubMed Web of Science ®Google Scholar
• Burrows, J.N., Duparc, S., Gutteridge, W.E., Hooft Van Huijsduijnen, R., Kaszubska, W., Macintyre, F., Mazzuri, S., Möhrle, J.J. & Wells, T.N.C. 2017. New developments in anti-malarial target candidate and product profiles. Malaria Journal 16: 26.
   PubMed Web of Science ®Google Scholar
• Cheuka, P.M., Lawrence, N., Taylor, D., Wittlin, S. & Chibale, K. 2018. Antiplasmodial imidazopyridazines: structure-activity relationship studies lead to the identification of analogues with improved solubility and hERG profiles. RSC Medicinal Chemistry - Royal Society of Chemistry 9: 1733–1745.
   Google Scholar
• Coertzen, D., Reader, J., Van Der Watt, M., Nondaba, S.H., Gibhard, L., Wiesner, L., Smith, P., D'alessandro, S., Taramelli, D., Wong, H.N., Du Preez, J.L., Wu, R.W.K., Birkholtz, L.-M. & Haynes, R.K. 2018. Artemisone and artemiside - potent pan-reactive antimalarial agents that also synergize redox imbalance in P. falciparum transmissible gametocyte stages. Antimicrob. Agents Chemother 62: e02214–17.
   PubMed Web of Science ®Google Scholar
• Coetzee, N., Von Grüning, H., Opperman, D., Van Der Watt, M., Reader, J. & Birkholtz, L.-M. 2020. Epigenetic inhibitors target multiple stages of Plasmodium falciparum parasites. Scientific Reports 10: 2355.
   PubMed Web of Science ®Google Scholar
• Duffy, S. & Avery, V.M. 2012. Development and optimization of a Novel 384-well anti-malarial imaging assay validated for high-throughput screening. The American Journal of Tropical Medicine and Hygiene 86: 84–92.
   PubMed Web of Science ®Google Scholar
• Fivelman, Q.L., Mcrobert, L., Sharp, S., Taylor, C.J., Saeed, M., Swales, C.A., Sutherland, C.J. & Baker, D.A. 2007. Improved synchronous production of Plasmodium falciparum gametocytes in vitro. Molecular and Biochemical Parasitology 154: 119–123.
   PubMed Web of Science ®Google Scholar
• González Cabrera, D., Horatscheck, A., Wilson, C.R., Basarab, G., Eyermann, C.J. & Chibale, K. 2018. Plasmodial Kinase inhibitors: License to cure? Journal of Medicinal Chemistry 61: 8061–8077.
   PubMed Web of Science ®Google Scholar
• Green, J.L., Moon, R.W., Whalley, D., Bowyer, P.W., Wallace, C., Rochani, A., Nageshan, R.K., Howell, S.A., Grainger, M., Jones, H.M., Ansell, K.H., Chapman, T.M., Taylor, D.L., Osborne, S.A., Baker, D.A., Tatu, U. & Holder, A.A. 2016. Imidazopyridazine inhibitors of Plasmodium falciparum calcium-dependent protein Kinase 1 also target cyclic GMP-dependent protein kinase and heat shock Protein 90 to kill the parasite at different stages of intracellular development. Antimicrobial Agents and Chemotherapy 60: 1464–1475.
   Web of Science ®Google Scholar
• Kini, S.G., Garg, V., Prasanna, S., Rajappan, R. & Mubeen, M. 2017. Protein kinases as drug targets in human and animal diseases. Current Enzyme Inhibition 13: 99–108.
   Google Scholar
• Le Manach, C., Gonzàlez Cabrera, D., Douelle, F., Nchinda, A.T., Younis, Y., Taylor, D., Wiesner, L., White, K.L., Ryan, E., March, C., Duffy, S., Avery, V.M., Waterson, D., Witty, M.J., Wittlin, S., Charman, S.A., Street, L.J. & Chibale, K. 2014a. medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a softfocus kinase library: part 1. Journal of Medicinal Chemistry 57: 2789–2798.
   PubMed Web of Science ®Google Scholar
• Le Manach, C., Paquet, T., Brunschwig, C., Njoroge, M., Han, Z., Gonzàlez Cabrera, D., Bashyam, S., Dhinakaran, R., Taylor, D., Reader, J., Botha, M., Churchyard, A., Lauterbach, S., Coetzer, T.L., Birkholtz, L.-M., Meister, S., Winzeler, E.A., Waterson, D., Witty, M.J., Wittlin, S., Jiménez-Díaz, M.-B., Santos Martínez, M., Ferrer, S., Angulo-Barturen, I., Street, L.J. & Chibale, K. 2015a. A Novel Pyrazolopyridine with in vivo activity in Plasmodium berghei- and Plasmodium falciparum-infected mouse models from structure–activity relationship studies around the core of recently identified antimalarial imidazopyridazines. Journal of Medicinal Chemistry 58: 8713–8722.
   PubMed Web of Science ®Google Scholar
• Le Manach, C., Paquet, T., Brunschwig, C., Njoroge, M., Han, Z., Gonzàlez Cabrera, D., Bashyam, S., Dhinakaran, R., Taylor, D., Reader, J., Botha, M., Churchyard, A., Lauterbach, S., Coetzer, T.L., Birkholtz, L.M., Meister, S., Winzeler, E.A., Waterson, D., Witty, M.J., Wittlin, S., Jiménez-Díaz, M.B., Santos Martínez, M., Ferrer, S., Angulo-Barturen, I., Street, L.J. & Chibale, K. 2015b. A novel pyrazolopyridine with in vivo activity in plasmodium berghei- and plasmodium falciparum-infected mouse models from structure-activity relationship studies around the core of recently identified antimalarial imidazopyridazines. J Med Chem 58: 8713–8722.
   PubMed Web of Science ®Google Scholar
• Le Manach, C., Paquet, T., Gonzàlez Cabrera, D., Younis, Y., Taylor, D., Wiesner, L., Lawrence, N., Schwager, S., Waterson, D., Witty, M.J., Wittlin, S., Street, L.J. & Chibale, K. 2014b. Medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a softfocus kinase library: part 2. Journal of Medicinal Chemistry 57: 8839–8848.
   PubMed Web of Science ®Google Scholar
• Lemercier, G., Fernandez-Montalvan, A., Shaw, J.P., Kugelstadt, D., Bomke, J., Domostoj, M., Schwarz, M.K., Scheer, A., Kappes, B. & Leroy, D. 2009. Identification and characterization of novel small molecules as potent inhibitors of the plasmodial calcium-dependent protein kinase 1. Biochemistry 48: 6379–6389.
   PubMed Web of Science ®Google Scholar
• Matsumoto, S., Miyamoto, N., Hirayama, T., Oki, H., Okada, K., Tawada, M., Iwata, H., Nakamura, K., Yamasaki, S., Miki, H., Hori, A. & Imamura, S. 2013. Structure-based design, synthesis, and evaluation of imidazo[1,2-b]pyridazine and imidazo[1,2-a]pyridine derivatives as novel dual c-Met and VEGFR2 kinase inhibitors. Bioorganic & Medicinal Chemistry 21: 7686–7698.
   PubMedGoogle Scholar
• Mcnamara, C. W., Lee, M. C. S., Lim, C. S., Lim, S. H., Roland, J., Nagle, A., Simon, O., Yeung, B. K. S., Chatterjee, A. K., Mccormack, S. L., Manary, M. J., Zeeman, A.-M., Dechering, K. J., Kumar, T. R. S., Henrich, P. P., Gagaring, K., Ibanez, M., Kato, N., Kuhen, K. L., Fischli, C., Rottmann, M., Plouffe, D. M., Bursulaya, B., Meister, S., Rameh, L., Trappe, J., Haasen, D., Timmerman, M., Sauerwein, R. W., Suwanarusk, R., Russell, B., Renia, L., Nosten, F., Tully, D. C., Kocken, C. H. M., Glynne, R. J., Bodenreider, C., Fidock, D. A., Diagana, T. T. & Winzeler, E. A. 2013. Targeting Plasmodium PI(4)K to eliminate malaria. Nature 504: 248-253.
   PubMed Web of Science ®Google Scholar
• Moran, D.B., Powell, D.W. & Albrigh, J.D. 1986. Imidazo[1,2-b] Pyridazine.
   Google Scholar
• Osborne, S., Chapman, T., Large, J., Bouloc, N. & Wallace, C. 2011. Fused Heterocyclic Compounds for Use in the Treatment of Malaria.
   Google Scholar
• Paquet, T., Le Manach, C., Cabrera, D.G., Younis, Y., Henrich, P.P., Abraham, T.S., Lee, M.C.S., Basak, R., Ghidelli-Disse, S., Lafuente-Monasterio, M.J., Bantscheff, M., Ruecker, A., Blagborough, A.M., Zakutansky, S.E., Zeeman, A.M., White, K.L., Shackleford, D.M., Mannila, J., Morizzi, J., Scheurer, C., Angulo-Barturen, I., Martínez, M.S., Ferrer, S., Sanz, L.M., Gamo, F.J., Reader, J., Botha, M., Dechering, K.J., Sauerwein, R.W., Tungtaeng, A., Vanachayangkul, P., Lim, C.S., Burrows, J., Witty, M.J., Marsh, K.C., Bodenreider, C., Rochford, R., Solapure, S.M., Jiménez-Díaz, M.B., Wittlin, S., Charman, S.A., Donini, C., Campo, B., Birkholtz, L.M., Hanson, K.K., Drewes, G., Kocken, C.H.M., Delves, M.J., Leroy, D., Fidock, D.A., Waterson, D., Street, L.J. & Chibale, K. 2017. Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci Transl Med 9 (387): eaad9735.
   PubMed Web of Science ®Google Scholar
• Plouffe, D.M., Wree, M., Du, A.Y., Meister, S., Li, F., Patra, K., Lubar, A., Okitsu, S.L., Flannery, E.L., Kato, N., Tanaseichuk, O., Comer, E., Zhou, B., Kuhen, K., Zhou, Y., Leroy, D., Schreiber, S.L., Scherer, C.A., Vinetz, J. & Winzeler, E.A. 2016. High-Throughput Assay and Discovery of Small Molecules that Interrupt Malaria Transmission. Cell Host & Microbe 19: 114–126.
   PubMed Web of Science ®Google Scholar
• Reader, J., Botha, M., Theron, A., Lauterbach, S.B., Rossouw, C., Engelbrecht, D., Wepener, M., Smit, A., Leroy, D., Mancama, D., Coetzer, L.C. & Birkholtz, L. 2015. Nowhere to hide: interrogating different metabolic parameters of Plasmodium falciparum gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination. Malaria Journal 14: 213.
   PubMed Web of Science ®Google Scholar
• Sahu, N.K., Shahi, S., Sharma, M.C. & Kohli, D.V. 2011. QSAR studies on imidazopyridazine derivatives as PfPK7 inhibitors. Molecular Simulation 37: 752–765.
   Web of Science ®Google Scholar
• Singh, K., Okombo, J., Brunschwig, C., Ndubi, F., Barnard, L., Wilkinson, C., Njogu, P.M., Njoroge, M., Laing, L., Machado, M., Prudêncio, M., Reader, J., Botha, M., Nondaba, S., Birkholtz, L.M., Lauterbach, S., Churchyard, A., Coetzer, T.L., Burrows, J.N., Yeates, C., Denti, P., Wiesner, L., Egan, T.J., Wittlin, S. & Chibale, K. 2017. Antimalarial Pyrido[1,2-a]benzimidazoles: lead optimization, parasite life cycle stage profile, mechanistic evaluation, killing kinetics, and in vivo oral efficacy in a mouse model. J Med Chem 60: 1432–1448.
   PubMed Web of Science ®Google Scholar
• Smilkstein, M., Sriwilaijaroen, N., Kelly, J.X., Wilairat, P. & Riscoe, M. 2004. Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrobial Agents and Chemotherapy 48: 1803–1806.
   PubMed Web of Science ®Google Scholar
• Van Biljon, R., Van Wyk, R., Painter, H.J., Orchard, L., Reader, J., Niemand, J., LlináS, M. & Birkholtz, L.M. 2019. Hierarchical transcriptional control regulates Plasmodium falciparum sexual differentiation. BMC Genomics 20: 920.
   PubMed Web of Science ®Google Scholar
• Van Der Watt, M.E., Reader, J., Churchyard, A., Nondaba, S.H., Lauterbach, S.B., Niemand, J., Abayomi, S., Van Biljon, R.A., Connacher, J.I., Van Wyk, R.D.J., Le Manach, C., Paquet, T., González Cabrera, D., Brunschwig, C., Theron, A., Lozano-Arias, S., Rodrigues, J.F.I., Herreros, E., Leroy, D., Duffy, J., Street, L.J., Chibale, K., Mancama, D., Coetzer, T.L. & Birkholtz, L.-M. 2018. Potent Plasmodium falciparum gametocytocidal compounds identified by exploring the kinase inhibitor chemical space for dual active antimalarials. Journal of Antimicrobial Chemotherapy 73: 1279–1290.
   PubMed Web of Science ®Google Scholar
• Verlinden, B.K., Niemand, J., Snyman, J., Sharma, S.K., Beattie, R.J., Woster, P.M. & Birkholtz, L. 2011. Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities. Journal of Medicinal Chemistry 54: 6624–6633.
   PubMed Web of Science ®Google Scholar
• Ward, P., Equinet, L., Packer, J. & Doerig, C. 2004. Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote. BMC Genomics 5: 79–79.
   PubMed Web of Science ®Google Scholar
• WHO. 2019. World Malaria Report 2019.
   Google Scholar
• Zhang, J., Yang, P.L. & Gray, N.S. 2009. Targeting cancer with small molecule kinase inhibitors. Nature Reviews Cancer 9: 28.
   PubMed Web of Science ®Google Scholar