Australian chemistry and drug discovery towards the development of antimalarials^†

References

[1]  WHO. World Malaria Report. Geneva: World Health Organization: Geneva, Switzerland; 2020. Available at https://www.who.int/publications/i/item/9789240015791

[2]  Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial Lancet 2015, 386, 31.
         | Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trialCrossref | GoogleScholarGoogle Scholar |

[3]  EA Ashley, M Dhorda, RM Fairhurst, C Amaratunga, P Lim, S Suon, S Sreng, JM Anderson, S Mao, B Sam, C Sopha, CM Chuor, C Nguon, S Sovannaroth, S Pukrittayakamee, P Jittamala, K Chotivanich, K Chutasmit, C Suchatsoonthorn, R Runcharoen, TT Hien, NT Thuy-Nhien, NV Thanh, NH Phu, Y Htut, KT Han, KH Aye, OA Mokuolu, RR Olaosebikan, OO Folaranmi, M Mayxay, M Khanthavong, B Hongvanthong, PN Newton, MA Onyamboko, CI Fanello, AK Tshefu, N Mishra, N Valecha, AP Phyo, F Nosten, P Yi, R Tripura, S Borrmann, M Bashraheil, J Peshu, MA Faiz, A Ghose, MA Hossain, R Samad, MR Rahman, MM Hasan, A Islam, O Miotto, R Amato, B MacInnis, J Stalker, DP Kwiatkowski, Z Bozdech, A Jeeyapant, PY Cheah, T Sakulthaew, J Chalk, B Intharabut, K Silamut, SJ Lee, B Vihokhern, C Kunasol, M Imwong, J Tarning, WJ Taylor, S Yeung, CJ Woodrow, JA Flegg, D Das, J Smith, M Venkatesan, CV Plowe, K Stepniewska, PJ Guerin, AM Dondorp, NP Day, NJ White, Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2014, 371, 411.
         | Spread of artemisinin resistance in Plasmodium falciparum malaria.Crossref | GoogleScholarGoogle Scholar |

[4]  A Uwimana, E Legrand, BH Stokes, J-LM Ndikumana, M Warsame, N Umulisa, D Ngamije, T Munyaneza, J-B Mazarati, K Munguti, P Campagne, A Criscuolo, F Ariey, M Murindahabi, P Ringwald, DA Fidock, A Mbituyumuremyi, D Menard, Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med 2020, 26, 1602.
         | Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda.Crossref | GoogleScholarGoogle Scholar |

[5]  JN Burrows, S Duparc, WE Gutteridge, R Hooft van Huijsduijnen, W Kaszubska, F Macintyre, S Mazzuri, JJ Möhrle, TNC Wells, New developments in anti-malarial target candidate and product profiles. Malar J 2017, 16, 26.
         | New developments in anti-malarial target candidate and product profiles.Crossref | GoogleScholarGoogle Scholar |

[6]  SA Charman, S Arbe-Barnes, IC Bathurst, R Brun, M Campbell, WN Charman, FCK Chiu, J Chollet, JC Craft, DJ Creek, Y Dong, H Matile, M Maurer, J Morizzi, T Nguyen, P Papastogiannidis, C Scheurer, DM Shackleford, K Sriraghavan, L Stingelin, Y Tang, H Urwyler, X Wang, KL White, S Wittlin, L Zhou, JL Vennerstrom, Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. Proc Natl Acad Sci U S A 2011, 108, 4400.
         | Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria.Crossref | GoogleScholarGoogle Scholar |

[7]  TD Ashton, SM Devine, JJ Möhrle, B Laleu, JN Burrows, SA Charman, DJ Creek, BE Sleebs, The development process for discovery and clinical advancement of modern antimalarials. J Med Chem 2019, 62, 10526.
         | The development process for discovery and clinical advancement of modern antimalarials.Crossref | GoogleScholarGoogle Scholar |

[8]  DL Doolan, Malaria research in Australia: looking through the lens of the past towards the future. Int J Parasitol 2021, 51, 1255.
         | Malaria research in Australia: looking through the lens of the past towards the future.Crossref | GoogleScholarGoogle Scholar |

[9]  S Duffy, VM Avery, Development and optimization of a novel 384-well anti-malarial imaging assay validated for high-throughput screening. Am J Trop Med Hyg 2012, 86, 84.
         | Development and optimization of a novel 384-well anti-malarial imaging assay validated for high-throughput screening.Crossref | GoogleScholarGoogle Scholar |

[10]  WA Guiguemde, AA Shelat, D Bouck, S Duffy, GJ Crowther, PH Davis, DC Smithson, M Connelly, J Clark, F Zhu, MB Jiménez-Díaz, MS Martinez, EB Wilson, AK Tripathi, J Gut, ER Sharlow, I Bathurst, F El Mazouni, JW Fowble, I Forquer, PL McGinley, S Castro, I Angulo-Barturen, S Ferrer, PJ Rosenthal, JL Derisi, DJ Sullivan, JS Lazo, DS Roos, MK Riscoe, MA Phillips, PK Rathod, WC Van Voorhis, VM Avery, RK Guy, Chemical genetics of Plasmodium falciparum. Nature 2010, 465, 311.
         | Chemical genetics of Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[11]  VM Avery, S Bashyam, JN Burrows, S Duffy, G Papadatos, S Puthukkuti, Y Sambandan, S Singh, T Spangenberg, D Waterson, P Willis, Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum. Malar J 2014, 13, 190.
         | Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[12]  C Le Manach, D Gonzàlez Cabrera, F Douelle, AT Nchinda, Y Younis, D Taylor, L Wiesner, KL White, E Ryan, C March, S Duffy, VM Avery, D Waterson, MJ Witty, S Wittlin, SA Charman, LJ Street, K Chibale, Medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a SoftFocus kinase library: part 1. J Med Chem 2014, 57, 2789.
         | Medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a SoftFocus kinase library: part 1.Crossref | GoogleScholarGoogle Scholar |

[13]  CD Edlin, G Morgans, S Winks, S Duffy, VM Avery, S Wittlin, D Waterson, J Burrows, J Bryans, Identification and in-vitro ADME assessment of a series of novel anti-malarial agents suitable for hit-to-lead chemistry. ACS Med Chem Lett 2012, 3, 570.
         | Identification and in-vitro ADME assessment of a series of novel anti-malarial agents suitable for hit-to-lead chemistry.Crossref | GoogleScholarGoogle Scholar |

[14]  S Duffy, VM Avery, Identification of inhibitors of Plasmodium falciparum gametocyte development. Malar J 2013, 12, 408.
         | Identification of inhibitors of Plasmodium falciparum gametocyte development.Crossref | GoogleScholarGoogle Scholar |

[15]  L Lucantoni, DA Fidock, VM Avery, Luciferase-based, high-throughput assay for screening and profiling transmission-blocking compounds against Plasmodium falciparum gametocytes. Antimicrob Agents Chemother 2016, 60, 2097.
         | Luciferase-based, high-throughput assay for screening and profiling transmission-blocking compounds against Plasmodium falciparum gametocytes.Crossref | GoogleScholarGoogle Scholar |

[16]  S Duffy, S Loganathan, JP Holleran, VM Avery, Large-scale production of Plasmodium falciparum gametocytes for malaria drug discovery. Nat Protoc 2016, 11, 976.
         | Large-scale production of Plasmodium falciparum gametocytes for malaria drug discovery.Crossref | GoogleScholarGoogle Scholar |

[17]  S Duffy, ML Sykes, AJ Jones, TB Shelper, M Simpson, R Lang, SA Poulsen, BE Sleebs, VM Avery, Screening the medicines for malaria venture pathogen box across multiple pathogens reclassifies starting points for open-source drug discovery. Antimicrob Agents Chemother 2017, 61, e00379-17.
         | Screening the medicines for malaria venture pathogen box across multiple pathogens reclassifies starting points for open-source drug discovery.Crossref | GoogleScholarGoogle Scholar |

[18]  L Lucantoni, F Silvestrini, M Signore, G Siciliano, M Eldering, KJ Dechering, VM Avery, P Alano, A simple and predictive phenotypic high content imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds. Sci Rep 2015, 5, 16414.
         | A simple and predictive phenotypic high content imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds.Crossref | GoogleScholarGoogle Scholar |

[19]  WC Van Voorhis, JH Adams, R Adelfio, V Ahyong, MH Akabas, P Alano, A Alday, Y Alemán Resto, A Alsibaee, A Alzualde, KT Andrews, SV Avery, VM Avery, L Ayong, M Baker, S Baker, C Ben Mamoun, S Bhatia, Q Bickle, L Bounaadja, T Bowling, J Bosch, LE Boucher, FF Boyom, J Brea, M Brennan, A Burton, CR Caffrey, G Camarda, M Carrasquilla, D Carter, M Belen Cassera, K Chih-Chien Cheng, W Chindaudomsate, A Chubb, BL Colon, DD Colón-López, Y Corbett, GJ Crowther, N Cowan, S D’Alessandro, N Le Dang, M Delves, JL DeRisi, AY Du, S Duffy, S Abd El-Salam El-Sayed, MT Ferdig, JA Fernández Robledo, DA Fidock, I Florent, PV Fokou, A Galstian, FJ Gamo, S Gokool, B Gold, T Golub, GM Goldgof, R Guha, WA Guiguemde, N Gural, RK Guy, MA Hansen, KK Hanson, A Hemphill, R Hooft van Huijsduijnen, T Horii, P Horrocks, TB Hughes, C Huston, I Igarashi, K Ingram-Sieber, MA Itoe, A Jadhav, A Naranuntarat Jensen, LT Jensen, RH Jiang, A Kaiser, J Keiser, T Ketas, S Kicka, S Kim, K Kirk, VP Kumar, DE Kyle, MJ Lafuente, S Landfear, N Lee, S Lee, AM Lehane, F Li, D Little, L Liu, M Llinás, MI Loza, A Lubar, L Lucantoni, I Lucet, L Maes, D Mancama, NR Mansour, S March, S McGowan, I Medina Vera, S Meister, L Mercer, J Mestres, AN Mfopa, RN Misra, S Moon, JP Moore, F Morais Rodrigues da Costa, J Müller, A Muriana, S Nakazawa Hewitt, B Nare, C Nathan, N Narraidoo, S Nawaratna, KK Ojo, D Ortiz, G Panic, G Papadatos, S Parapini, K Patra, N Pham, S Prats, DM Plouffe, SA Poulsen, A Pradhan, C Quevedo, RJ Quinn, CA Rice, M Abdo Rizk, A Ruecker St, R Onge, R Salgado Ferreira, J Samra, NG Robinett, U Schlecht, M Schmitt, F Silva Villela, F Silvestrini, R Sinden, DA Smith, T Soldati, A Spitzmüller, SM Stamm, DJ Sullivan, W Sullivan, S Suresh, BM Suzuki, Y Suzuki, SJ Swamidass, D Taramelli, LR Tchokouaha, A Theron, D Thomas, KF Tonissen, S Townson, AK Tripathi, V Trofimov, KO Udenze, I Ullah, C Vallieres, E Vigil, JM Vinetz, P Voong Vinh, H Vu, NA Watanabe, K Weatherby, PM White, AF Wilks, EA Winzeler, E Wojcik, M Wree, W Wu, N Yokoyama, PH Zollo, N Abla, B Blasco, J Burrows, B Laleu, D Leroy, T Spangenberg, T Wells, PA Willis, Open source drug discovery with the malaria box compound collection for neglected diseases and beyond. PLoS Pathog 2016, 12, e1005763.
         | Open source drug discovery with the malaria box compound collection for neglected diseases and beyond.Crossref | GoogleScholarGoogle Scholar |

[20]  L Lucantoni, S Duffy, SH Adjalley, DA Fidock, VM Avery, Identification of MMV malaria box inhibitors of Plasmodium falciparum early-stage gametocytes using a luciferase-based high-throughput assay. Antimicrob Agents Chemother 2013, 57, 6050.
         | Identification of MMV malaria box inhibitors of Plasmodium falciparum early-stage gametocytes using a luciferase-based high-throughput assay.Crossref | GoogleScholarGoogle Scholar |

[21]  O Looker, MG Dans, HE Bullen, BE Sleebs, BS Crabb, PR Gilson, The medicines for malaria venture malaria box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites. Traffic 2022,
         | The medicines for malaria venture malaria box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites.Crossref | GoogleScholarGoogle Scholar |

[22]  MG Dans, GE Weiss, DW Wilson, BE Sleebs, BS Crabb, TF de Koning-Ward, PR Gilson, Screening the medicines for malaria venture pathogen box for invasion and egress inhibitors of the blood stage of Plasmodium falciparum reveals several inhibitory compounds. Int J Parasitol 2020, 50, 235.
         | Screening the medicines for malaria venture pathogen box for invasion and egress inhibitors of the blood stage of Plasmodium falciparum reveals several inhibitory compounds.Crossref | GoogleScholarGoogle Scholar |

[23]  BK Dickerman, B Elsworth, SA Cobbold, CQ Nie, MJ McConville, BS Crabb, PR Gilson, Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum. Sci Rep 2016, 6, 37502.
         | Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[24]  NJ Spillman, RJW Allen, CW McNamara, BKS Yeung, EA Winzeler, TT Diagana, K Kirk, Na+ regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials. Cell Host Microbe 2013, 13, 227.
         | Na⁺ regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials.Crossref | GoogleScholarGoogle Scholar |

[25]  MB Jiménez-Díaz, D Ebert, Y Salinas, A Pradhan, AM Lehane, ME Myrand-Lapierre, KG O’Loughlin, DM Shackleford, M Justino de Almeida, AK Carrillo, JA Clark, AS Dennis, J Diep, X Deng, S Duffy, AN Endsley, G Fedewa, WA Guiguemde, MG Gómez, G Holbrook, J Horst, CC Kim, J Liu, MC Lee, A Matheny, MS Martínez, G Miller, A Rodríguez-Alejandre, L Sanz, M Sigal, NJ Spillman, PD Stein, Z Wang, F Zhu, D Waterson, S Knapp, A Shelat, VM Avery, DA Fidock, FJ Gamo, SA Charman, JC Mirsalis, H Ma, S Ferrer, K Kirk, I Angulo-Barturen, DE Kyle, JL DeRisi, DM Floyd, RK Guy, (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. Proc Natl Acad Sci U S A 2014, 111, E5455.
         | (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium.Crossref | GoogleScholarGoogle Scholar |

[26]  NJ Spillman, RJW Allen, K Kirk, Na+ extrusion imposes an acid load on the intraerythrocytic malaria parasite. Mol Biochem Parasitol 2013, 189, 1.
         | Na⁺ extrusion imposes an acid load on the intraerythrocytic malaria parasite.Crossref | GoogleScholarGoogle Scholar |

[27]  AM Lehane, MC Ridgway, E Baker, K Kirk, Diverse chemotypes disrupt ion homeostasis in the malaria parasite. Mol Microbiol 2014, 94, 327.
         | Diverse chemotypes disrupt ion homeostasis in the malaria parasite.Crossref | GoogleScholarGoogle Scholar |

[28]  JEO Rosling, MC Ridgway, RL Summers, K Kirk, AM Lehane, Biochemical characterization and chemical inhibition of PfATP4-associated Na+-ATPase activity in Plasmodium falciparum membranes. J Biol Chem 2018, 293, 13327.
         | Biochemical characterization and chemical inhibition of PfATP4-associated Na⁺-ATPase activity in Plasmodium falciparum membranes.Crossref | GoogleScholarGoogle Scholar |

[29]  ASM Dennis, JEO Rosling, AM Lehane, K Kirk, Diverse antimalarials from whole-cell phenotypic screens disrupt malaria parasite ion and volume homeostasis. Sci Rep 2018, 8, 8795.
         | Diverse antimalarials from whole-cell phenotypic screens disrupt malaria parasite ion and volume homeostasis.Crossref | GoogleScholarGoogle Scholar |

[30]  SV Hapuarachchi, SA Cobbold, SH Shafik, AS Dennis, MJ McConville, RE Martin, K Kirk, AM Lehane, The malaria parasite’s lactate transporter PfFNT is the target of antiplasmodial compounds identified in whole cell phenotypic screens. PLoS Pathog 2017, 13, e1006180.
         | The malaria parasite’s lactate transporter PfFNT is the target of antiplasmodial compounds identified in whole cell phenotypic screens.Crossref | GoogleScholarGoogle Scholar |

[31]  RV Marchetti, AM Lehane, SH Shafik, M Winterberg, RE Martin, K Kirk, A lactate and formate transporter in the intraerythrocytic malaria parasite, Plasmodium falciparum. Nat Commun 2015, 6, 6721.
         | A lactate and formate transporter in the intraerythrocytic malaria parasite, Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[32]  E Yeh, JL DeRisi, Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum. PLoS Biol 2011, 9, e1001138.
         | Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[33]  T Uddin, GI McFadden, CD Goodman, Validation of putative apicoplast-targeting drugs using a chemical supplementation assay in cultured human malaria parasites. Antimicrob Agents Chemother 2018, 62, e01161-17.
         | Validation of putative apicoplast-targeting drugs using a chemical supplementation assay in cultured human malaria parasites.Crossref | GoogleScholarGoogle Scholar |

[34]  A Paiardini, RS Bamert, K Kannan-Sivaraman, N Drinkwater, SN Mistry, PJ Scammells, S McGowan, Screening the medicines for malaria venture "malaria box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18. PLoS One 2015, 10, e0115859.
         | Screening the medicines for malaria venture "malaria box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18.Crossref | Plasmodium falciparum aminopeptidases, M1, M17 and M18.&journal=PLoS One&volume=10&pages=e0115859-&publication_year=2015&author=A%20Paiardini&hl=en&doi=10.1371/journal.pone.0115859" target="_blank" rel="nofollow noopener noreferrer" class="reftools">GoogleScholarGoogle Scholar |

[35]  IS Lucet, A Tobin, D Drewry, AF Wilks, C Doerig, Plasmodium kinases as targets for new-generation antimalarials. Future Med Chem 2012, 4, 2295.
         | Plasmodium kinases as targets for new-generation antimalarials.Crossref | GoogleScholarGoogle Scholar |

[36]  BE Sleebs, KE Jarman, S Frolich, W Wong, J Healer, W Dai, IS Lucet, DW Wilson, AF Cowman, Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein. Int J Parasitol Drugs Drug Resist 2020, 14, 188.
         | Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein.Crossref | GoogleScholarGoogle Scholar |

[37]  H Vu, L Pedro, T Mak, B McCormick, J Rowley, M Liu, A Di Capua, B Williams-Noonan, NB Pham, R Pouwer, B Nguyen, KT Andrews, T Skinner-Adams, J Kim, WGJ Hol, R Hui, GJ Crowther, WC Van Voorhis, RJ Quinn, Fragment-based screening of a natural product library against 62 potential malaria drug targets employing native mass spectrometry. ACS Infect Dis 2018, 4, 431.
         | Fragment-based screening of a natural product library against 62 potential malaria drug targets employing native mass spectrometry.Crossref | GoogleScholarGoogle Scholar |

[38]  H Vu, C Roullier, M Campitelli, KR Trenholme, DL Gardiner, KT Andrews, T Skinner-Adams, GJ Crowther, WC Van Voorhis, RJ Quinn, Plasmodium gametocyte inhibition identified from a natural-product-based fragment library. ACS Chem Biol 2013, 8, 2654.
         | Plasmodium gametocyte inhibition identified from a natural-product-based fragment library.Crossref | GoogleScholarGoogle Scholar |

[39]  SA Cobbold, MJ McConville, Determining the mode of action of antimalarial drugs using time-resolved LC-MS-based metabolite profiling. Methods Mol Biol 2019, 1859, 225.
         | Determining the mode of action of antimalarial drugs using time-resolved LC-MS-based metabolite profiling.Crossref | GoogleScholarGoogle Scholar |

[40]  SA Cobbold, HH Chua, B Nijagal, DJ Creek, SA Ralph, MJ McConville, Metabolic dysregulation induced in Plasmodium falciparum by dihydroartemisinin and other front-line antimalarial drugs. J Infect Dis 2016, 213, 276.
         | Metabolic dysregulation induced in Plasmodium falciparum by dihydroartemisinin and other front-line antimalarial drugs.Crossref | GoogleScholarGoogle Scholar |

[41]  G Siddiqui, C Giannangelo, A De Paoli, AK Schuh, KC Heimsch, D Anderson, TG Brown, CA MacRaild, J Wu, X Wang, Y Dong, JL Vennerstrom, K Becker, DJ Creek, Peroxide antimalarial drugs target redox homeostasis in Plasmodium falciparum infected red blood cells. ACS Infect Dis 2022, 8, 210.
         | Peroxide antimalarial drugs target redox homeostasis in Plasmodium falciparum infected red blood cells.Crossref | GoogleScholarGoogle Scholar |

[42]  C Giannangelo, G Siddiqui, A De Paoli, BM Anderson, LE Edgington-Mitchell, SA Charman, DJ Creek, System-wide biochemical analysis reveals ozonide antimalarials initially act by disrupting Plasmodium falciparum haemoglobin digestion. PLoS Pathog 2020, 16, e1008485.
         | System-wide biochemical analysis reveals ozonide antimalarials initially act by disrupting Plasmodium falciparum haemoglobin digestion.Crossref | GoogleScholarGoogle Scholar |

[43]  GW Birrell, MP Challis, A De Paoli, D Anderson, SM Devine, GD Heffernan, DP Jacobus, MD Edstein, G Siddiqui, DJ Creek, Multi-omic characterization of the mode of action of a potent new antimalarial compound, JPC-3210, against Plasmodium falciparum. Mol Cell Proteomics 2020, 19, 308.
         | Multi-omic characterization of the mode of action of a potent new antimalarial compound, JPC-3210, against Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[44]  G Siddiqui, A Srivastava, AS Russell, DJ Creek, Multi-omics based identification of specific biochemical changes associated with PfKelch13-mutant artemisinin-resistant Plasmodium falciparum. J Infect Dis 2017, 215, 1435.
         | Multi-omics based identification of specific biochemical changes associated with PfKelch13-mutant artemisinin-resistant Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[45]  DJ Creek, HH Chua, SA Cobbold, B Nijagal, JI MacRae, BK Dickerman, PR Gilson, SA Ralph, MJ McConville, Metabolomics-based screening of the malaria box reveals both novel and established mechanisms of action. Antimicrob Agents Chemother 2016, 60, 6650.
         | Metabolomics-based screening of the malaria box reveals both novel and established mechanisms of action.Crossref | GoogleScholarGoogle Scholar |

[46]  SA Charman, A Andreu, H Barker, S Blundell, A Campbell, M Campbell, G Chen, FCK Chiu, E Crighton, K Katneni, J Morizzi, R Patil, T Pham, E Ryan, J Saunders, DM Shackleford, KL White, L Almond, M Dickins, DA Smith, JJ Moehrle, JN Burrows, N Abla, An in vitro toolbox to accelerate anti-malarial drug discovery and development. Malar J 2020, 19, 1.
         | An in vitro toolbox to accelerate anti-malarial drug discovery and development.Crossref | GoogleScholarGoogle Scholar |

[47]  Y Dong, S Wittlin, K Sriraghavan, J Chollet, SA Charman, WN Charman, C Scheurer, H Urwyler, J Santo Tomas, C Snyder, DJ Creek, J Morizzi, M Koltun, H Matile, X Wang, M Padmanilayam, Y Tang, A Dorn, R Brun, JL Vennerstrom, The structure−activity relationship of the antimalarial ozonide arterolane (OZ277). J Med Chem 2010, 53, 481.
         | The structure−activity relationship of the antimalarial ozonide arterolane (OZ277).Crossref | GoogleScholarGoogle Scholar |

[48]  Y Dong, X Wang, S Kamaraj, VJ Bulbule, FCK Chiu, J Chollet, M Dhanasekaran, CD Hein, P Papastogiannidis, J Morizzi, DM Shackleford, H Barker, E Ryan, C Scheurer, Y Tang, Q Zhao, L Zhou, KL White, H Urwyler, WN Charman, H Matile, S Wittlin, SA Charman, JL Vennerstrom, Structure–activity relationship of the antimalarial ozonide artefenomel (OZ439). J Med Chem 2017, 60, 2654.
         | Structure–activity relationship of the antimalarial ozonide artefenomel (OZ439).Crossref | GoogleScholarGoogle Scholar |

[49]  JJ Moehrle, S Duparc, C Siethoff, PL van Giersbergen, JC Craft, S Arbe-Barnes, SA Charman, M Gutierrez, S Wittlin, JL Vennerstrom, First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials. Br J Clin Pharmacol 2013, 75, 524.
         | First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials.Crossref | GoogleScholarGoogle Scholar |

[50]  MA Phillips, J Lotharius, K Marsh, J White, A Dayan, KL White, JW Njoroge, F El Mazouni, Y Lao, S Kokkonda, DR Tomchick, X Deng, T Laird, SN Bhatia, S March, CL Ng, DA Fidock, S Wittlin, M Lafuente-Monasterio, FJ Benito, LM Alonso, MS Martinez, MB Jimenez-Diaz, SF Bazaga, I Angulo-Barturen, JN Haselden, J Louttit, Y Cui, A Sridhar, AM Zeeman, C Kocken, R Sauerwein, K Dechering, VM Avery, S Duffy, M Delves, R Sinden, A Ruecker, KS Wickham, R Rochford, J Gahagen, L Iyer, E Riccio, J Mirsalis, I Bathhurst, T Rueckle, X Ding, B Campo, D Leroy, MJ Rogers, PK Rathod, JN Burrows, SA Charman, A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Sci Transl Med 2015, 7, 296ra111.
         | A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria.Crossref | GoogleScholarGoogle Scholar |

[51]  MA Phillips, KL White, S Kokkonda, X Deng, J White, F El Mazouni, K Marsh, DR Tomchick, K Manjalanagara, KR Rudra, G Wirjanata, R Noviyanti, RN Price, J Marfurt, DM Shackleford, FCK Chiu, M Campbell, MB Jimenez-Diaz, SF Bazaga, I Angulo-Barturen, MS Martinez, M Lafuente-Monasterio, W Kaminsky, K Silue, AM Zeeman, C Kocken, D Leroy, B Blasco, E Rossignol, T Rueckle, D Matthews, JN Burrows, D Waterson, MJ Palmer, PK Rathod, SA Charman, A triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with improved drug-like properties for treatment and prevention of malaria. ACS Infect Dis 2016, 2, 945.
         | A triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with improved drug-like properties for treatment and prevention of malaria.Crossref | GoogleScholarGoogle Scholar |

[52]  T Paquet, C Le Manach, DG Cabrera, Y Younis, PP Henrich, TS Abraham, MCS Lee, R Basak, S Ghidelli-Disse, MJ Lafuente-Monasterio, M Bantscheff, A Ruecker, AM Blagborough, SE Zakutansky, AM Zeeman, KL White, DM Shackleford, J Mannila, J Morizzi, C Scheurer, I Angulo-Barturen, MS Martínez, S Ferrer, LM Sanz, FJ Gamo, J Reader, M Botha, KJ Dechering, RW Sauerwein, A Tungtaeng, P Vanachayangkul, CS Lim, J Burrows, MJ Witty, KC Marsh, C Bodenreider, R Rochford, SM Solapure, MB Jiménez-Díaz, S Wittlin, SA Charman, C Donini, B Campo, LM Birkholtz, KK Hanson, G Drewes, CHM Kocken, MJ Delves, D Leroy, DA Fidock, D Waterson, LJ Street, K Chibale, Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci Transl Med 2017, 9, eaad9735.
         | Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase.Crossref | GoogleScholarGoogle Scholar |

[53]  C Brunschwig, N Lawrence, D Taylor, E Abay, M Njoroge, GS Basarab, C Le Manach, T Paquet, DG Cabrera, AT Nchinda, C de Kock, L Wiesner, P Denti, D Waterson, B Blasco, D Leroy, MJ Witty, C Donini, J Duffy, S Wittlin, KL White, SA Charman, MB Jiménez-Díaz, I Angulo-Barturen, E Herreros, FJ Gamo, R Rochford, D Mancama, TL Coetzer, ME van der Watt, J Reader, LM Birkholtz, KC Marsh, SM Solapure, JE Burke, JA McPhail, M Vanaerschot, DA Fidock, PV Fish, P Siegl, DA Smith, G Wirjanata, R Noviyanti, RN Price, J Marfurt, KD Silue, LJ Street, K Chibale, UCT943, a next-generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria. Antimicrob Agents Chemother 2018, 62, e00012-18.
         | UCT943, a next-generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria.Crossref | GoogleScholarGoogle Scholar |

[54]  KA Collins, AN Abd-Rahman, L Marquart, E Ballard, N Gobeau, P Griffin, S Chalon, JJ Möhrle, JS McCarthy, Antimalarial activity of artefenomel against asexual parasites and transmissible gametocytes during experimental blood-stage Plasmodium vivax infection. J Infect Dis 2022, 225, 1062.
         | Antimalarial activity of artefenomel against asexual parasites and transmissible gametocytes during experimental blood-stage Plasmodium vivax infection.Crossref | GoogleScholarGoogle Scholar |

[55]  JS McCarthy, M Baker, P O’Rourke, L Marquart, P Griffin, R Hooft van Huijsduijnen, JJ Möhrle, J Antimicrob Chemother 2016, 71, 2620.
         | Crossref | GoogleScholarGoogle Scholar |

[56]  JS McCarthy, AN Abd-Rahman, KA Collins, L Marquart, P Griffin, A Kümmel, A Fuchs, C Winnips, V Mishra, K Csermak-Renner, JP Jain, P Gandhi, Defining the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum. Antimicrob Agents Chemother 2021, 65, e01423-20.
         | Defining the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[57]  JS McCarthy, T Rückle, SL Elliott, E Ballard, KA Collins, L Marquart, P Griffin, S Chalon, JJ Möhrle, A single-dose combination study with the experimental antimalarials artefenomel and DSM265 to determine safety and antimalarial activity against blood-stage Plasmodium falciparum in healthy volunteers. Antimicrob Agents Chemother 2019, 64, e01371-19.
         | A single-dose combination study with the experimental antimalarials artefenomel and DSM265 to determine safety and antimalarial activity against blood-stage Plasmodium falciparum in healthy volunteers.Crossref | GoogleScholarGoogle Scholar |

[58]  KA Collins, T Rückle, S Elliott, L Marquart, E Ballard, S Chalon, P Griffin, JJ Möhrle, JS McCarthy, DSM265 at 400 milligrams clears asexual stage parasites but not mature gametocytes from the blood of healthy subjects experimentally infected with Plasmodium falciparum. Antimicrob Agents Chemother 2019, 63, e01837-18.
         | DSM265 at 400 milligrams clears asexual stage parasites but not mature gametocytes from the blood of healthy subjects experimentally infected with Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[59]  P Sinxadi, C Donini, H Johnstone, G Langdon, L Wiesner, E Allen, S Duparc, S Chalon, JS McCarthy, U Lorch, K Chibale, J Möhrle, KI Barnes, Safety, tolerability, pharmacokinetics, and antimalarial activity of the novel Plasmodium phosphatidylinositol 4-kinase inhibitor MMV390048 in healthy volunteers. Antimicrob Agents Chemother 2020, 64, e01896-19.
         | Safety, tolerability, pharmacokinetics, and antimalarial activity of the novel Plasmodium phosphatidylinositol 4-kinase inhibitor MMV390048 in healthy volunteers.Crossref | GoogleScholarGoogle Scholar |

[60]  JS McCarthy, C Donini, S Chalon, J Woodford, L Marquart, KA Collins, FD Rozenberg, DA Fidock, MH Cherkaoui-Rbati, N Gobeau, JJ Möhrle, A Phase 1, placebo-controlled, randomized, single ascending dose study and a volunteer infection study to characterize the safety, pharmacokinetics, and antimalarial activity of the Plasmodium phosphatidylinositol 4-kinase inhibitor MMV390048. Clin Infect Dis 2020, 71, e657.
         | A Phase 1, placebo-controlled, randomized, single ascending dose study and a volunteer infection study to characterize the safety, pharmacokinetics, and antimalarial activity of the Plasmodium phosphatidylinositol 4-kinase inhibitor MMV390048.Crossref | GoogleScholarGoogle Scholar |

[61]  AH Gaur, JS McCarthy, JC Panetta, RH Dallas, J Woodford, L Tang, AM Smith, TB Stewart, KC Branum, BB Freeman III, ND Patel, E John, S Chalon, S Ost, RN Heine, JL Richardson, R Christensen, PM Flynn, Y Van Gessel, B Mitasev, JJ Möhrle, F Gusovsky, L Bebrevska, RK Guy, Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial. Lancet Infect Dis 2020, 20, 964.
         | Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial.Crossref | GoogleScholarGoogle Scholar |

[62]  A Krause, J Dingemanse, A Mathis, L Marquart, JJ Möhrle, JS McCarthy, Pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of Actelion-451840 in an induced blood stage malaria study in healthy subjects Br J Clin Pharmacol 2016, 82, 412.
         | Pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of Actelion-451840 in an induced blood stage malaria study in healthy subjectsCrossref | GoogleScholarGoogle Scholar |

[63]  BE Barber, M Fernandez, HB Patel, C Barcelo, SD Woolley, H Patel, S Llewellyn, AN Abd-Rahman, S Sharma, M Jain, A Ghoghari, I Di Resta, A Fuchs, I Deni, T Yeo, S Mok, DA Fidock, S Chalon, JJ Möhrle, D Parmar, JS McCarthy, K Kansagra, Safety, pharmacokinetics, and antimalarial activity of the novel triaminopyrimidine ZY-19489: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study, pilot food-effect study, and volunteer infection study. Lancet Infect Dis 2022, 22, 879.
         | Safety, pharmacokinetics, and antimalarial activity of the novel triaminopyrimidine ZY-19489: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study, pilot food-effect study, and volunteer infection study.Crossref | GoogleScholarGoogle Scholar |

[64]  RA Davis, MS Buchanan, S Duffy, VM Avery, SA Charman, WN Charman, KL White, DM Shackleford, MD Edstein, KT Andrews, D Camp, RJ Quinn, Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp. J Med Chem 2012, 55, 5851.
         | Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp.Crossref | GoogleScholarGoogle Scholar |

[65]  MSJ Arnold, JR Macdonald, RJ Quinn, TS Skinner-Adams, KT Andrews, GM Fisher, Antiplasmodial activity of the natural product compounds alstonine and himbeline. Int J Parasitol Drugs Drug Resist 2021, 16, 17.
         | Antiplasmodial activity of the natural product compounds alstonine and himbeline.Crossref | GoogleScholarGoogle Scholar |

[66]  R Kumar, S Duffy, VM Avery, RA Davis, Synthesis of antimalarial amide analogues based on the plant serrulatane diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid. Bioorg Med Chem Lett 2017, 27, 4091.
         | Synthesis of antimalarial amide analogues based on the plant serrulatane diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid.Crossref | GoogleScholarGoogle Scholar |

[67]  RA Davis, S Duffy, S Fletcher, VM Avery, RJ Quinn, Thiaplakortones A–D: antimalarial thiazine alkaloids from the Australian marine sponge Plakortis lita. J Org Chem 2013, 78, 9608.
         | Thiaplakortones A–D: antimalarial thiazine alkaloids from the Australian marine sponge Plakortis lita.Crossref | GoogleScholarGoogle Scholar |

[68]  RH Pouwer, SM Deydier, PV Le, BD Schwartz, NC Franken, RA Davis, MJ Coster, SA Charman, MD Edstein, TS Skinner-Adams, KT Andrews, ID Jenkins, RJ Quinn, Total synthesis of thiaplakortone A: derivatives as metabolically stable leads for the treatment of malaria. ACS Med Chem Lett 2013, 5, 178.
         | Total synthesis of thiaplakortone A: derivatives as metabolically stable leads for the treatment of malaria.Crossref | GoogleScholarGoogle Scholar |

[69]  BD Schwartz, TS Skinner-Adams, KT Andrews, MJ Coster, MD Edstein, D MacKenzie, SA Charman, M Koltun, S Blundell, A Campbell, RH Pouwer, RJ Quinn, KD Beattie, PC Healy, RA Davis, Synthesis and antimalarial evaluation of amide and urea derivatives based on the thiaplakortone A natural product scaffold. Org Biomol Chem 2015, 13, 1558.
         | Synthesis and antimalarial evaluation of amide and urea derivatives based on the thiaplakortone A natural product scaffold.Crossref | GoogleScholarGoogle Scholar |

[70]  S Johnson, R Rahmani, DR Drew, MJ Williams, M Wilkinson, YH Tan, JX Huang, CJ Tonkin, JG Beeson, J Baum, BJ Smith, JB Baell, Truncated latrunculins as actin inhibitors targeting Plasmodium falciparum motility and host cell invasion. J Med Chem 2016, 59, 10994.
         | Truncated latrunculins as actin inhibitors targeting Plasmodium falciparum motility and host cell invasion.Crossref | GoogleScholarGoogle Scholar |

[71]  T Conroy, JT Guo, NH Hunt, RJ Payne, Total synthesis and antimalarial activity of symplostatin 4. Org Lett 2010, 12, 5576.
         | Total synthesis and antimalarial activity of symplostatin 4.Crossref | GoogleScholarGoogle Scholar |

[72]  T Conroy, JT Guo, RG Linington, NH Hunt, RJ Payne, Total synthesis, stereochemical assignment, and antimalarial activity of gallinamide A. Chemistry 2011, 17, 13544.
         | Total synthesis, stereochemical assignment, and antimalarial activity of gallinamide A.Crossref | GoogleScholarGoogle Scholar |

[73]  T Conroy, JT Guo, N Elias, KM Cergol, J Gut, J Legac, L Khatoon, Y Liu, S McGowan, PJ Rosenthal, NH Hunt, RJ Payne, Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials. J Med Chem 2014, 57, 10557.
         | Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials.Crossref | GoogleScholarGoogle Scholar |

[74]  K Ban, S Duffy, Y Khakham, VM Avery, A Hughes, O Montagnat, K Katneni, E Ryan, JB Baell, 3-alkylthio-1,2,4-triazine dimers with potent antimalarial activity. Bioorg Med Chem Lett 2010, 20, 6024.
         | 3-alkylthio-1,2,4-triazine dimers with potent antimalarial activity.Crossref | GoogleScholarGoogle Scholar |

[75]  KM Katherine, L Lucantoni, M Chavchich, M Abraham, A De Paoli, MR Luth, A-M Zeeman, MJ Delves, FS-R Terán, U Straschil, J Baum, CHM Kocken, SA Ralph, EA Winzeler, VM Avery, MD Edstein, JB Baell, DJ Creek, The novel bis-1,2,4-triazine MIPS-0004373 demonstrates rapid and potent activity against all blood stages of the malaria parasite. Antimicrob Agents Chemother 65, e00311-21.
         | The novel bis-1,2,4-triazine MIPS-0004373 demonstrates rapid and potent activity against all blood stages of the malaria parasite.Crossref | GoogleScholarGoogle Scholar |

[76]  L Xue, D-H Shi, JR Harjani, F Huang, JG Beveridge, T Dingjan, K Ban, S Diab, S Duffy, L Lucantoni, S Fletcher, FCK Chiu, S Blundell, K Ellis, SA Ralph, G Wirjanata, S Teguh, R Noviyanti, M Chavchich, D Creek, RN Price, J Marfurt, SA Charman, ME Cuellar, JM Strasser, JL Dahlin, MA Walters, MD Edstein, VM Avery, JB Baell, 3,3′-disubstituted 5,5′-Bi(1,2,4-triazine) derivatives with potent in vitro and in vivo antimalarial activity. J Med Chem 2019, 62, 2485.
         | 3,3′-disubstituted 5,5′-Bi(1,2,4-triazine) derivatives with potent in vitro and in vivo antimalarial activity.Crossref | GoogleScholarGoogle Scholar |

[77]  DL Priebbenow, M Mathiew, D-H Shi, JR Harjani, JG Beveridge, M Chavchich, MD Edstein, S Duffy, VM Avery, RT Jacobs, S Brand, DM Shackleford, W Wang, L Zhong, G Lee, E Tay, H Barker, E Crighton, KL White, SA Charman, A De Paoli, DJ Creek, JB Baell, Discovery of potent and fast-acting antimalarial Bis-1,2,4-triazines. J Med Chem 2021, 64, 4150.
         | Discovery of potent and fast-acting antimalarial Bis-1,2,4-triazines.Crossref | GoogleScholarGoogle Scholar |

[78]  AE Williamson, PM Ylioja, MN Robertson, Y Antonova-Koch, V Avery, JB Baell, H Batchu, S Batra, JN Burrows, S Bhattacharyya, F Calderon, SA Charman, J Clark, B Crespo, M Dean, SL Debbert, M Delves, ASM Dennis, F Deroose, S Duffy, S Fletcher, G Giaever, I Hallyburton, F-J Gamo, M Gebbia, RK Guy, Z Hungerford, K Kirk, MJ Lafuente-Monasterio, A Lee, S Meister, C Nislow, JP Overington, G Papadatos, L Patiny, J Pham, SA Ralph, A Ruecker, E Ryan, C Southan, K Srivastava, C Swain, MJ Tarnowski, P Thomson, P Turner, IM Wallace, TNC Wells, K White, L White, P Willis, EA Winzeler, S Wittlin, MH Todd, Open source drug discovery: highly potent antimalarial compounds derived from the Tres Cantos arylpyrroles. ACS Cent Sci 2016, 2, 687.
         | Open source drug discovery: highly potent antimalarial compounds derived from the Tres Cantos arylpyrroles.Crossref | GoogleScholarGoogle Scholar |

[79]  EG Tse, L Aithani, M Anderson, J Cardoso-Silva, G Cincilla, GJ Conduit, M Galushka, D Guan, I Hallyburton, BWJ Irwin, K Kirk, AM Lehane, JCR Lindblom, R Lui, S Matthews, J McCulloch, A Motion, HL Ng, M Öeren, MN Robertson, V Spadavecchio, VA Tatsis, WP van Hoorn, AD Wade, TM Whitehead, P Willis, MH Todd, An open drug discovery competition: experimental validation of predictive models in a series of novel antimalarials. J Med Chem 2021, 64, 16450.
         | An open drug discovery competition: experimental validation of predictive models in a series of novel antimalarials.Crossref | GoogleScholarGoogle Scholar |

[80]  PR Gilson, W Nguyen, WA Poole, JE Teixeira, JK Thompson, K Guo, RJ Stewart, TD Ashton, KL White, LM Sanz, FJ Gamo, SA Charman, S Wittlin, J Duffy, CJ Tonkin, WH Tham, BS Crabb, BM Cooke, CD Huston, AF Cowman, BE Sleebs, Evaluation of 4-amino 2-anilinoquinazolines against Plasmodium and other apicomplexan parasites in vitro and in a P. falciparum humanized NOD-scid IL2Rγnull mouse model of malaria. Antimicrob Agents Chemother 2019, 63, e01804-18.
         | Evaluation of 4-amino 2-anilinoquinazolines against Plasmodium and other apicomplexan parasites in vitro and in a P. falciparum humanized NOD-scid IL2Rγ^null mouse model of malaria.Crossref | GoogleScholarGoogle Scholar |

[81]  PR Gilson, C Tan, KE Jarman, KN Lowes, JM Curtis, W Nguyen, AE Di Rago, HE Bullen, B Prinz, S Duffy, JB Baell, CA Hutton, H Jousset Subroux, BS Crabb, VM Avery, AF Cowman, BE Sleebs, Optimization of 2-anilino 4-amino substituted quinazolines into potent antimalarial agents with oral in vivo activity. J Med Chem 2017, 60, 1171.
         | Optimization of 2-anilino 4-amino substituted quinazolines into potent antimalarial agents with oral in vivo activity.Crossref | GoogleScholarGoogle Scholar |

[82]  TD Ashton, A Ngo, P Favuzza, HE Bullen, MR Gancheva, O Romeo, M Parkyn Schneider, N Nguyen, RWJ Steel, S Duffy, KN Lowes, HJ Sabroux, VM Avery, JA Boddey, DW Wilson, AF Cowman, PR Gilson, BE Sleebs, Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity. Bioorg Chem 2021, 117, 105359.
         | Property activity refinement of 2-anilino 4-amino substituted quinazolines as antimalarials with fast acting asexual parasite activity.Crossref | GoogleScholarGoogle Scholar |

[83]  W Nguyen, MG Dans, A Ngo, MR Gancheva, O Romeo, S Duffy, TF de Koning-Ward, KN Lowes, HJ Sabroux, VM Avery, DW Wilson, PR Gilson, BE Sleebs, Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion. Eur J Med Chem 2021, 214, 113253.
         | Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion.Crossref | GoogleScholarGoogle Scholar |

[84]  BL Bailey, W Nguyen, A Ngo, CD Goodman, MR Gancheva, P Favuzza, LM Sanz, FJ Gamo, KN Lowes, GI McFadden, DW Wilson, B Laleu, S Brand, PF Jackson, AF Cowman, BE Sleebs, Optimisation of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity. Bioorg Chem 2021, 115, 105244.
         | Optimisation of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity.Crossref | GoogleScholarGoogle Scholar |

[85]  MJ Buskes, KL Harvey, B Prinz, BS Crabb, PR Gilson, DJD Wilson, BM Abbott, Exploration of 3-methylisoquinoline-4-carbonitriles as protein kinase A inhibitors of Plasmodium falciparum. Bioorg Med Chem 2016, 24, 2389.
         | Exploration of 3-methylisoquinoline-4-carbonitriles as protein kinase A inhibitors of Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[86]  MJ Buskes, KL Harvey, BJ Richards, R Kalhor, RM Christoff, CK Gardhi, DR Littler, ED Cope, B Prinz, GE Weiss, NJ O’Brien, BS Crabb, LW Deady, PR Gilson, BM Abbott, Antimalarial activity of novel 4-cyano-3-methylisoquinoline inhibitors against Plasmodium falciparum: design, synthesis and biological evaluation. Org Biomol Chem 2016, 14, 4617.
         | Antimalarial activity of novel 4-cyano-3-methylisoquinoline inhibitors against Plasmodium falciparum: design, synthesis and biological evaluation.Crossref | GoogleScholarGoogle Scholar |

[87]  PR Gilson, R Kumarasingha, J Thompson, X Zhang, JS Penington, R Kalhor, HE Bullen, AM Lehane, MG Dans, TF de Koning-Ward, JK Holien, TP Soares da Costa, MD Hulett, MJ Buskes, BS Crabb, K Kirk, AT Papenfuss, AF Cowman, BM Abbott, A 4-cyano-3-methylisoquinoline inhibitor of Plasmodium falciparum growth targets the sodium efflux pump PfATP4. Sci Rep 2019, 9, 10292.

[88]  B Krishnarjuna, SS Lim, SM Devine, CO Debono, R Lam, IR Chandrashekaran, G Jaipuria, H Yagi, HS Atreya, MJ Scanlon, CA MacRaild, PJ Scammells, RS Norton, Solution NMR characterization of apical membrane antigen 1 and small molecule interactions as a basis for designing new antimalarials. J Mol Recognit 2016, 29, 281.
         | Solution NMR characterization of apical membrane antigen 1 and small molecule interactions as a basis for designing new antimalarials.Crossref | GoogleScholarGoogle Scholar |

[89]  SM Devine, MP Challis, JK Kigotho, G Siddiqui, A De Paoli, CA MacRaild, VM Avery, DJ Creek, RS Norton, PJ Scammells, Discovery and development of 2-aminobenzimidazoles as potent antimalarials. Eur J Med Chem 2021, 221, 113518.
         | Discovery and development of 2-aminobenzimidazoles as potent antimalarials.Crossref | GoogleScholarGoogle Scholar |

[90]  D Hocková, A Holý, M Masojídková, DT Keough, J de Jersey, LW Guddat, Synthesis of branched 9-[2-(2-phosphonoethoxy)ethyl]purines as a new class of acyclic nucleoside phosphonates which inhibit Plasmodium falciparum hypoxanthine–guanine–xanthine phosphoribosyltransferase. Bioorg Med Chem 2009, 17, 6218.
         | Synthesis of branched 9-[2-(2-phosphonoethoxy)ethyl]purines as a new class of acyclic nucleoside phosphonates which inhibit Plasmodium falciparum hypoxanthine–guanine–xanthine phosphoribosyltransferase.Crossref | GoogleScholarGoogle Scholar |

[91]  P Špaček, DT Keough, M Chavchich, M Dračínský, Z Janeba, L Naesens, MD Edstein, LW Guddat, D Hocková, J Med Chem 2017, 60, 7539.
         | Crossref | GoogleScholarGoogle Scholar |

[92]  J Frydrych, DT Keough, M Chavchich, J Travis, M Dračínský, MD Edstein, LW Guddat, D Hocková, Z Janeba, Nucleotide analogues containing a pyrrolidine, piperidine or piperazine ring: synthesis and evaluation of inhibition of plasmodial and human 6-oxopurine phosphoribosyltransferases and in vitro antimalarial activity. Eur J Med Chem 2021, 219, 113416.
         | Nucleotide analogues containing a pyrrolidine, piperidine or piperazine ring: synthesis and evaluation of inhibition of plasmodial and human 6-oxopurine phosphoribosyltransferases and in vitro antimalarial activity.Crossref | GoogleScholarGoogle Scholar |

[93]  T Klejch, DT Keough, M Chavchich, J Travis, J Skácel, R Pohl, Z Janeba, MD Edstein, VM Avery, LW Guddat, D Hocková, Sulfide, sulfoxide and sulfone bridged acyclic nucleoside phosphonates as inhibitors of the Plasmodium falciparum and human 6-oxopurine phosphoribosyltransferases: Synthesis and evaluation. Eur J Med Chem 2019, 183, 111667.
         | Sulfide, sulfoxide and sulfone bridged acyclic nucleoside phosphonates as inhibitors of the Plasmodium falciparum and human 6-oxopurine phosphoribosyltransferases: Synthesis and evaluation.Crossref | GoogleScholarGoogle Scholar |

[94]  MM Kaiser, D Hocková, TH Wang, M Dračínský, L Poštová-Slavětínská, E Procházková, MD Edstein, M Chavchich, DT Keough, LW Guddat, Z Janeba, Synthesis and evaluation of novel acyclic nucleoside phosphonates as inhibitors of Plasmodium falciparum and human 6-oxopurine phosphoribosyltransferases. ChemMedChem 2015, 10, 1707.
         | Synthesis and evaluation of novel acyclic nucleoside phosphonates as inhibitors of Plasmodium falciparum and human 6-oxopurine phosphoribosyltransferases.Crossref | GoogleScholarGoogle Scholar |

[95]  DT Keough, D Rejman, R Pohl, E Zborníková, D Hocková, T Croll, MD Edstein, GW Birrell, M Chavchich, LMJ Naesens, GK Pierens, IM Brereton, LW Guddat, Design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics. ACS Chem Biol 2018, 13, 82.
         | Design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics.Crossref | GoogleScholarGoogle Scholar |

[96]  TS Skinner-Adams, CM Stack, KR Trenholme, CL Brown, J Grembecka, J Lowther, A Mucha, M Drag, P Kafarski, S McGowan, JC Whisstock, DL Gardiner, JP Dalton, Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends Biochem Sci 2010, 35, 53.
         | Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials.Crossref | GoogleScholarGoogle Scholar |

[97]  TS Skinner-Adams, J Lowther, F Teuscher, CM Stack, J Grembecka, A Mucha, P Kafarski, KR Trenholme, JP Dalton, DL Gardiner, Identification of phosphinate dipeptide analog inhibitors directed against the Plasmodium falciparum M17 leucine aminopeptidase as lead antimalarial compounds. J Med Chem 2007, 50, 6024.
         | Identification of phosphinate dipeptide analog inhibitors directed against the Plasmodium falciparum M17 leucine aminopeptidase as lead antimalarial compounds.Crossref | GoogleScholarGoogle Scholar |

[98]  CM Stack, J Lowther, E Cunningham, S Donnelly, DL Gardiner, KR Trenholme, TS Skinner-Adams, F Teuscher, J Grembecka, A Mucha, P Kafarski, L Lua, A Bell, JP Dalton, Characterization of the Plasmodium falciparum M17 leucyl aminopeptidase: a protease involved in amino acid regulation with potential for antimalarial drug development. J Biol Chem 2007, 282, 2069.
         | Characterization of the Plasmodium falciparum M17 leucyl aminopeptidase: a protease involved in amino acid regulation with potential for antimalarial drug development.Crossref | GoogleScholarGoogle Scholar |

[99]  N Drinkwater, RS Bamert, KK Sivaraman, A Paiardini, S McGowan, X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17. Proteins 2015, 83, 789.
         | X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.Crossref | GoogleScholarGoogle Scholar |

[100]  S McGowan, CA Oellig, WA Birru, TT Caradoc-Davies, CM Stack, J Lowther, T Skinner-Adams, A Mucha, P Kafarski, J Grembecka, KR Trenholme, AM Buckle, DL Gardiner, JP Dalton, JC Whisstock, Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases. Proc Natl Acad Sci U S A 2010, 107, 2449.
         | Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases.Crossref | GoogleScholarGoogle Scholar |

[101]  S McGowan, CJ Porter, J Lowther, CM Stack, SJ Golding, TS Skinner-Adams, KR Trenholme, F Teuscher, SM Donnelly, J Grembecka, A Mucha, P Kafarski, R Degori, AM Buckle, DL Gardiner, JC Whisstock, JP Dalton, Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase. Proc Natl Acad Sci U S A 2009, 106, 2537.
         | Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.Crossref | GoogleScholarGoogle Scholar |

[102]  K Kannan Sivaraman, A Paiardini, M Sieńczyk, C Ruggeri, CA Oellig, JP Dalton, PJ Scammells, M Drag, S McGowan, Synthesis and structure–activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum. J Med Chem 2013, 56, 5213.
         | Synthesis and structure–activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.Crossref | GoogleScholarGoogle Scholar |

[103]  NB Vinh, N Drinkwater, TR Malcolm, M Kassiou, L Lucantoni, PM Grin, GS Butler, S Duffy, CM Overall, VM Avery, PJ Scammells, S McGowan, Hydroxamic acid inhibitors provide cross-species inhibition of Plasmodium M1 and M17 aminopeptidases. J Med Chem 2019, 62, 622.
         | Hydroxamic acid inhibitors provide cross-species inhibition of Plasmodium M1 and M17 aminopeptidases.Crossref | GoogleScholarGoogle Scholar |

[104]  N Drinkwater, NB Vinh, SN Mistry, RS Bamert, C Ruggeri, JP Holleran, S Loganathan, A Paiardini, SA Charman, AK Powell, VM Avery, S McGowan, PJ Scammells, Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions. Eur J Med Chem 2016, 110, 43.
         | Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions.Crossref | GoogleScholarGoogle Scholar |

[105]  TS Skinner-Adams, GM Fisher, AG Riches, OE Hutt, KE Jarvis, T Wilson, M von Itzstein, P Chopra, Y Antonova-Koch, S Meister, EA Winzeler, M Clarke, DA Fidock, JN Burrows, JH Ryan, KT Andrews, Cyclization-blocked proguanil as a strategy to improve the antimalarial activity of atovaquone. Commun Biol 2019, 2, 166.
         | Cyclization-blocked proguanil as a strategy to improve the antimalarial activity of atovaquone.Crossref | GoogleScholarGoogle Scholar |

[106]  BL Howard, KL Harvey, RJ Stewart, MF Azevedo, BS Crabb, IG Jennings, PR Sanders, DT Manallack, PE Thompson, CJ Tonkin, PR Gilson, Identification of potent phosphodiesterase inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites. ACS Chem Biol 2015, 10, 1145.
         | Identification of potent phosphodiesterase inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites.Crossref | GoogleScholarGoogle Scholar |

[107]  C Dogovski, SC Xie, G Burgio, J Bridgford, S Mok, JM McCaw, K Chotivanich, S Kenny, N Gnädig, J Straimer, Z Bozdech, DA Fidock, JA Simpson, AM Dondorp, S Foote, N Klonis, L Tilley, Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance. PLoS Biol 2015, 13, e1002132.
         | Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance.Crossref | GoogleScholarGoogle Scholar |

[108]  SC Xie, DL Gillett, NJ Spillman, C Tsu, MR Luth, S Ottilie, S Duffy, AE Gould, P Hales, BA Seager, CL Charron, F Bruzzese, X Yang, X Zhao, S-C Huang, CA Hutton, JN Burrows, EA Winzeler, VM Avery, LR Dick, L Tilley, Target validation and identification of novel boronate inhibitors of the Plasmodium falciparum proteasome. J Med Chem 2018, 61, 10053.
         | Target validation and identification of novel boronate inhibitors of the Plasmodium falciparum proteasome.Crossref | GoogleScholarGoogle Scholar |

[109]  C Xie Stanley, D Metcalfe Riley, H Mizutani, T Puhalovich, E Hanssen, J Morton Craig, Y Du, C Dogovski, S-C Huang, J Ciavarri, P Hales, J Griffin Robert, H Cohen Lawrence, B-C Chuang, S Wittlin, I Deni, T Yeo, E Ward Kurt, C Barry Daniel, B Liu, L Gillett David, F Crespo-Fernandez Benigno, S Ottilie, N Mittal, A Churchyard, D Ferguson, C Aguiar Anna Caroline, VC Guido Rafael, J Baum, K Hanson Kirsten, A Winzeler Elizabeth, F-J Gamo, A Fidock David, D Baud, W Parker Michael, S Brand, R Dick Lawrence, DW Griffin Michael, E Gould Alexandra, L Tilley, Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome. Proc Natl Acad Sci U S A 2021, 118, e2107213118.
         | Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome.Crossref | GoogleScholarGoogle Scholar |

[110]  SC Xie, RD Metcalfe, E Dunn, CJ Morton, SC Huang, T Puhalovich, Y Du, S Wittlin, S Nie, MR Luth, L Ma, MS Kim, CFA Pasaje, K Kumpornsin, C Giannangelo, FJ Houghton, A Churchyard, MT Famodimu, DC Barry, DL Gillett, S Dey, CC Kosasih, W Newman, JC Niles, MCS Lee, J Baum, S Ottilie, EA Winzeler, DJ Creek, N Williamson, MW Parker, S Brand, SP Langston, LR Dick, MDW Griffin, AE Gould, L Tilley, Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy. Science 2022, 376, 1074.
         | Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.Crossref | GoogleScholarGoogle Scholar |

[111]  JA Boddey, AN Hodder, S Günther, PR Gilson, H Patsiouras, EA Kapp, JA Pearce, TF de Koning-Ward, RJ Simpson, BS Crabb, AF Cowman, An aspartyl protease directs malaria effector proteins to the host cell. Nature 2010, 463, 627.
         | An aspartyl protease directs malaria effector proteins to the host cell.Crossref | GoogleScholarGoogle Scholar |

[112]  BE Sleebs, M Gazdik, MT O’Neill, P Rajasekaran, S Lopaticki, K Lackovic, K Lowes, BJ Smith, AF Cowman, JA Boddey, Transition state mimetics of the Plasmodium export element are potent inhibitors of plasmepsin V from P. falciparum and P. vivax. J Med Chem 2014, 57, 7644.
         | Transition state mimetics of the Plasmodium export element are potent inhibitors of plasmepsin V from P. falciparum and P. vivax.Crossref | GoogleScholarGoogle Scholar |

[113]  BE Sleebs, S Lopaticki, DS Marapana, MT O’Neill, P Rajasekaran, M Gazdik, S Gunther, LW Whitehead, KN Lowes, L Barfod, L Hviid, PJ Shaw, AN Hodder, BJ Smith, AF Cowman, JA Boddey, Inhibition of plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites. PLoS Biol 2014, 12, e1001897.
         | Inhibition of plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites.Crossref | GoogleScholarGoogle Scholar |

[114]  AN Hodder, BE Sleebs, PE Czabotar, M Gazdik, Y Xu, MT O’Neill, S Lopaticki, T Nebl, T Triglia, BJ Smith, K Lowes, JA Boddey, AF Cowman, Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes. Nat Struct Mol Biol 2015, 22, 590.
         | Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes.Crossref | GoogleScholarGoogle Scholar |

[115]  W Nguyen, AN Hodder, RB de Lezongard, PE Czabotar, KE Jarman, MT O’Neill, JK Thompson, H Jousset Sabroux, AF Cowman, JA Boddey, BE Sleebs, Enhanced antimalarial activity of plasmepsin V inhibitors by modification of the P2 position of PEXEL peptidomimetics. Eur J Med Chem 2018, 154, 182.
         | Enhanced antimalarial activity of plasmepsin V inhibitors by modification of the P₂ position of PEXEL peptidomimetics.Crossref | GoogleScholarGoogle Scholar |

[116]  M Gazdik, KE Jarman, MT O’Neill, AN Hodder, KN Lowes, H Jousset Sabroux, AF Cowman, JA Boddey, BE Sleebs, Exploration of the P3 region of PEXEL peptidomimetics leads to a potent inhibitor of the Plasmodium protease, plasmepsin V. Bioorg Med Chem 2016, 24, 1993.
         | Exploration of the P₃ region of PEXEL peptidomimetics leads to a potent inhibitor of the Plasmodium protease, plasmepsin V.Crossref | GoogleScholarGoogle Scholar |

[117]  M Gazdik, MT O’Neill, S Lopaticki, KN Lowes, BJ Smith, AF Cowman, JA Boddey, BE Sleebs, The effect of N-methylation on transition state mimetic inhibitors of the Plasmodium protease, plasmepsin V. MedChemComm 2015, 6, 437.
         | The effect of N-methylation on transition state mimetic inhibitors of the Plasmodium protease, plasmepsin V.Crossref | GoogleScholarGoogle Scholar |

[118]  C Jennison, L Lucantoni, MT O’Neill, R McConville, SM Erickson, AF Cowman, BE Sleebs, VM Avery, JA Boddey, Inhibition of plasmepsin V activity blocks Plasmodium falciparum gametocytogenesis and transmission to mosquitoes. Cell Rep 2019, 29, 3796.
         | Inhibition of plasmepsin V activity blocks Plasmodium falciparum gametocytogenesis and transmission to mosquitoes.Crossref | GoogleScholarGoogle Scholar |

[119]  P Favuzza, M de Lera Ruiz, JK Thompson, T Triglia, A Ngo, RWJ Steel, M Vavrek, J Christensen, J Healer, C Boyce, Z Guo, M Hu, T Khan, N Murgolo, L Zhao, JS Penington, K Reaksudsan, K Jarman, MH Dietrich, L Richardson, KY Guo, S Lopaticki, WH Tham, M Rottmann, T Papenfuss, JA Robbins, JA Boddey, BE Sleebs, HJ Sabroux, JA McCauley, DB Olsen, AF Cowman, Dual plasmepsin-targeting antimalarial agents disrupt multiple stages of the malaria parasite life cycle. Cell Host Microbe 2020, 27, 642.
         | Dual plasmepsin-targeting antimalarial agents disrupt multiple stages of the malaria parasite life cycle.Crossref | GoogleScholarGoogle Scholar |

[120]  AN Hodder, JJ Christensen, S Scally, T Triglia, A Ngo, RW Birkinshaw, B Bailey, P Favuzza, MH Dietrich, WH Tham, PE Czabotar, K Lowes, K Guo, N Murgolo, ML Ruiz, JA McCauley, BE Sleebs, DB Olsen, AF Cowman, Basis for drug selectivity of plasmepsin IX and X inhibition in Plasmodium falciparum and vivax. Structure 2022, 30, 947.
         | Basis for drug selectivity of plasmepsin IX and X inhibition in Plasmodium falciparum and vivax.Crossref | GoogleScholarGoogle Scholar |