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Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

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Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, U.K.
*Phone: +44 1382 386 240. E-mail: [email protected]
Cite this: J. Med. Chem. 2012, 55, 1, 140–152
Publication Date (Web):December 7, 2011
https://doi.org/10.1021/jm201091t

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Abstract

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N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.

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Synthetic details for all compounds, additional compound biological data (Tables S1–S4), and X-ray crystallographic data (Tables S5 and S6). This material is available free of charge via the Internet at http://pubs.acs.org.

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  8. Anja C. Schlott, Anthony A. Holder, Edward W. Tate. N-Myristoylation as a Drug Target in Malaria: Exploring the Role of N-Myristoyltransferase Substrates in the Inhibitor Mode of Action. ACS Infectious Diseases 2018, 4 (4) , 449-457. https://doi.org/10.1021/acsinfecdis.7b00203
  9. Hong Jiang, Xiaoyu Zhang, Xiao Chen, Pornpun Aramsangtienchai, Zhen Tong, and Hening Lin . Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies. Chemical Reviews 2018, 118 (3) , 919-988. https://doi.org/10.1021/acs.chemrev.6b00750
  10. Tracy Bayliss, David A. Robinson, Victoria C. Smith, Stephen Brand, Stuart P. McElroy, Leah S. Torrie, Chido Mpamhanga, Suzanne Norval, Laste Stojanovski, Ruth Brenk, Julie A. Frearson, Kevin D. Read, Ian H. Gilbert, and Paul G. Wyatt . Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors. Journal of Medicinal Chemistry 2017, 60 (23) , 9790-9806. https://doi.org/10.1021/acs.jmedchem.7b01255
  11. Stephanie Russell, Raphaël Rahmani, Amy J. Jones, Harriet L. Newson, Kevin Neilde, Ignacio Cotillo, Marzieh Rahmani Khajouei, Lori Ferrins, Sana Qureishi, Nghi Nguyen, Maria S. Martinez-Martinez, Donald F. Weaver, Marcel Kaiser, Jennifer Riley, John Thomas, Manu De Rycker, Kevin D. Read, Gavin R. Flematti, Eileen Ryan, Scott Tanghe, Ana Rodriguez, Susan A. Charman, Albane Kessler, Vicky M. Avery, Jonathan B. Baell, and Matthew J. Piggott . Hit-to-Lead Optimization of a Novel Class of Potent, Broad-Spectrum Trypanosomacides. Journal of Medicinal Chemistry 2016, 59 (21) , 9686-9720. https://doi.org/10.1021/acs.jmedchem.6b00442
  12. Megan H. Wright, Daniel Paape, Helen P. Price, Deborah F. Smith, and Edward W. Tate . Global Profiling and Inhibition of Protein Lipidation in Vector and Host Stages of the Sleeping Sickness Parasite Trypanosoma brucei. ACS Infectious Diseases 2016, 2 (6) , 427-441. https://doi.org/10.1021/acsinfecdis.6b00034
  13. Laura A. T. Cleghorn, Sébastien Albrecht, Laste Stojanovski, Frederick R. J. Simeons, Suzanne Norval, Robert Kime, Iain T. Collie, Manu De Rycker, Lorna Campbell, Irene Hallyburton, Julie A. Frearson, Paul G. Wyatt, Kevin D. Read, and Ian H. Gilbert . Discovery of Indoline-2-carboxamide Derivatives as a New Class of Brain-Penetrant Inhibitors of Trypanosoma brucei. Journal of Medicinal Chemistry 2015, 58 (19) , 7695-7706. https://doi.org/10.1021/acs.jmedchem.5b00596
  14. Stephen Brand, Neil R. Norcross, Stephen Thompson, Justin R. Harrison, Victoria C. Smith, David A. Robinson, Leah S. Torrie, Stuart P. McElroy, Irene Hallyburton, Suzanne Norval, Paul Scullion, Laste Stojanovski, Frederick R. C. Simeons, Daan van Aalten, Julie A. Frearson, Ruth Brenk, Alan H. Fairlamb, Michael A. J. Ferguson, Paul G. Wyatt, Ian H. Gilbert, and Kevin D. Read . Lead Optimization of a Pyrazole Sulfonamide Series of Trypanosoma brucei N-Myristoyltransferase Inhibitors: Identification and Evaluation of CNS Penetrant Compounds as Potential Treatments for Stage 2 Human African Trypanosomiasis. Journal of Medicinal Chemistry 2014, 57 (23) , 9855-9869. https://doi.org/10.1021/jm500809c
  15. Mathew Njoroge, Nicholas M. Njuguna, Peggoty Mutai, Dennis S. B. Ongarora, Paul W. Smith, and Kelly Chibale . Recent Approaches to Chemical Discovery and Development Against Malaria and the Neglected Tropical Diseases Human African Trypanosomiasis and Schistosomiasis. Chemical Reviews 2014, 114 (22) , 11138-11163. https://doi.org/10.1021/cr500098f
  16. Advait S. Nagle, Shilpi Khare, Arun Babu Kumar, Frantisek Supek, Andriy Buchynskyy, Casey J. N. Mathison, Naveen Kumar Chennamaneni, Nagendar Pendem, Frederick S. Buckner, Michael H. Gelb, and Valentina Molteni . Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis. Chemical Reviews 2014, 114 (22) , 11305-11347. https://doi.org/10.1021/cr500365f
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  18. Ian H. Gilbert . Drug Discovery for Neglected Diseases: Molecular Target-Based and Phenotypic Approaches. Journal of Medicinal Chemistry 2013, 56 (20) , 7719-7726. https://doi.org/10.1021/jm400362b
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  30. Ashwani Kumar, Jayant Sindhu, Parvin Kumar. In-silico identification of fingerprint of pyrazolyl sulfonamide responsible for inhibition of N -myristoyltransferase using Monte Carlo method with index of ideality of correlation. Journal of Biomolecular Structure and Dynamics 2021, 39 (14) , 5014-5025. https://doi.org/10.1080/07391102.2020.1784286
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  37. Larisa A. Baeva, Radik M. Nugumanov, Rail R. Gataullin, Akhnef А. Fatykhov. Reaction of 3-[(alkylsulfanyl)methyl]pentane-2,4-diones with nicotinic hydrazide. Chemistry of Heterocyclic Compounds 2020, 56 (5) , 548-554. https://doi.org/10.1007/s10593-020-02698-1
  38. María Álvarez-Bardón, Yolanda Pérez-Pertejo, César Ordóñez, Daniel Sepúlveda-Crespo, Nestor M. Carballeira, Babu L. Tekwani, Sankaranarayanan Murugesan, Maria Martinez-Valladares, Carlos García-Estrada, Rosa M. Reguera, Rafael Balaña-Fouce. Screening Marine Natural Products for New Drug Leads against Trypanosomatids and Malaria. Marine Drugs 2020, 18 (4) , 187. https://doi.org/10.3390/md18040187
  39. Baljinder Singh, Frederick S. Buckner, Michael P. Pollastri. Discovery of Drugs for Leishmaniases: A Progress Report. 2019, 139-160. https://doi.org/10.1002/9783527808656.ch6
  40. Marija K. Zacharova, Lindsay B. Tulloch, Eoin R. Gould, Andrew L. Fraser, Elizabeth F. King, Stefanie K. Menzies, Terry K. Smith, Gordon J. Florence. Structure‐Based Design, Synthesis and Biological Evaluation of Bis‐Tetrahydropyran Furan Acetogenin Mimics Targeting the Trypanosomatid F1 Component of ATP Synthase. European Journal of Organic Chemistry 2019, 2019 (31-32) , 5434-5440. https://doi.org/10.1002/ejoc.201900541
  41. Wouter W. Kallemeijn, Gregor A. Lueg, Monica Faronato, Kate Hadavizadeh, Andrea Goya Grocin, Ok-Ryul Song, Michael Howell, Dinis P. Calado, Edward W. Tate. Validation and Invalidation of Chemical Probes for the Human N-myristoyltransferases. Cell Chemical Biology 2019, 26 (6) , 892-900.e4. https://doi.org/10.1016/j.chembiol.2019.03.006
  42. Clinton G. L. Veale. Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease. ChemMedChem 2019, 14 (4) , 386-453. https://doi.org/10.1002/cmdc.201800755
  43. Vijay H. Masand, Nahed N.E. El-Sayed, Mukesh U. Bambole, Vaijant R. Patil, Sumer D. Thakur. Multiple quantitative structure-activity relationships (QSARs) analysis for orally active trypanocidal N-myristoyltransferase inhibitors. Journal of Molecular Structure 2019, 1175 , 481-487. https://doi.org/10.1016/j.molstruc.2018.07.080
  44. Clinton G. L. Veale, Heinrich C. Hoppe. Screening of the Pathogen Box reveals new starting points for anti-trypanosomal drug discovery. MedChemComm 2018, 9 (12) , 2037-2044. https://doi.org/10.1039/C8MD00319J
  45. Irena Corbic Ramljak, Julia Stanger, Antonio Real-Hohn, Dominik Dreier, Laurin Wimmer, Monika Redlberger-Fritz, Wolfgang Fischl, Karin Klingel, Marko D. Mihovilovic, Dieter Blaas, Heinrich Kowalski, . Cellular N-myristoyltransferases play a crucial picornavirus genus-specific role in viral assembly, virion maturation, and infectivity. PLOS Pathogens 2018, 14 (8) , e1007203. https://doi.org/10.1371/journal.ppat.1007203
  46. Noemi de J. Hiller, Nayane A. A. e Silva, Robson X. Faria, André Luís A. Souza, Jackson A. L. C. Resende, André Borges Farias, Nelilma Correia Romeiro, Daniela de Luna Martins. Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins. ChemMedChem 2018, 13 (14) , 1395-1404. https://doi.org/10.1002/cmdc.201800206
  47. Baoen Chen, Yang Sun, Jixiao Niu, Gopala K. Jarugumilli, Xu Wu. Protein Lipidation in Cell Signaling and Diseases: Function, Regulation, and Therapeutic Opportunities. Cell Chemical Biology 2018, 25 (7) , 817-831. https://doi.org/10.1016/j.chembiol.2018.05.003
  48. Luciana Scotti, Hamilton Ishiki, Francisco Jaime Bezerra Mendonça Junior, Frederico Fávaro Ribeiro, Nagendra Sastry Yarla, Marcelo Sobral da Silva, José Maria Barbosa Filho, Marcus Tullius Scotti. Computational and Metabolic Studies on a Set of N-Myristoyltransferase Inhibitors Against Trypanosoma Brucei. International Journal of Quantitative Structure-Property Relationships 2018, 3 (2) , 80-94. https://doi.org/10.4018/IJQSPR.2018070106
  49. L. A. Baeva, R. M. Nugumanov, A. A. Fatykhov, N. K. Lyapina. Synthesis of 4-[Alkylsulfanyl(sulfonyl)methyl]isoxazoles and -1H-pyrazoles from 3-[(Alkylsulfanyl)methyl]- pentane-2,4-diones. Russian Journal of Organic Chemistry 2018, 54 (3) , 444-451. https://doi.org/10.1134/S1070428018030120
  50. MARKUS RITZEFELD, MEGAN H. WRIGHT, EDWARD W. TATE. New developments in probing and targeting protein acylation in malaria, leishmaniasis and African sleeping sickness. Parasitology 2018, 145 (2) , 157-174. https://doi.org/10.1017/S0031182017000282
  51. Mark C. Field, David Horn, Alan H. Fairlamb, Michael A. J. Ferguson, David W. Gray, Kevin D. Read, Manu De Rycker, Leah S. Torrie, Paul G. Wyatt, Susan Wyllie, Ian H. Gilbert. Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nature Reviews Microbiology 2017, 15 (4) , 217-231. https://doi.org/10.1038/nrmicro.2016.193
  52. R.T. Jacobs. Antiparasitic Agents. 2017, 717-750. https://doi.org/10.1016/B978-0-12-409547-2.12411-4
  53. Michael Berninger, Ines Schmidt, Alicia Ponte-Sucre, Ulrike Holzgrabe. Novel lead compounds in pre-clinical development against African sleeping sickness. MedChemComm 2017, 8 (10) , 1872-1890. https://doi.org/10.1039/C7MD00280G
  54. Ifedayo Ogungbe, William Setzer. The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases—Part III: In-Silico Molecular Docking Investigations. Molecules 2016, 21 (10) , 1389. https://doi.org/10.3390/molecules21101389
  55. Daniela Begolo, Christine Clayton. Discovery of the Mechanism of Action of Novel Compounds That Target Unicellular Eukaryotic Parasites. 2016, 1-39. https://doi.org/10.1002/9783527694082.ch1
  56. K. Hemalatha, G. Madhumitha, Lokesh Ravi, V. Gopiesh Khanna, Naif Abdullah Al-Dhabi, Mariadhas Valan Arasu. Binding mode of dihydroquinazolinones with lysozyme and its antifungal activity against Aspergillus species. Journal of Photochemistry and Photobiology B: Biology 2016, 161 , 71-79. https://doi.org/10.1016/j.jphotobiol.2016.05.005
  57. Abu Salah Ud-Din, Alexandra Tikhomirova, Anna Roujeinikova. Structure and Functional Diversity of GCN5-Related N-Acetyltransferases (GNAT). International Journal of Molecular Sciences 2016, 17 (7) , 1018. https://doi.org/10.3390/ijms17071018
  58. Linda J. Herrera, Stephen Brand, Andres Santos, Lilian L. Nohara, Justin Harrison, Neil R. Norcross, Stephen Thompson, Victoria Smith, Carolina Lema, Armando Varela-Ramirez, Ian H. Gilbert, Igor C. Almeida, Rosa A. Maldonado, . Validation of N-myristoyltransferase as Potential Chemotherapeutic Target in Mammal-Dwelling Stages of Trypanosoma cruzi. PLOS Neglected Tropical Diseases 2016, 10 (4) , e0004540. https://doi.org/10.1371/journal.pntd.0004540
  59. Nidhi Singh, Priyanka Shah, Hemlata Dwivedi, Shikha Mishra, Renu Tripathi, Amogh A. Sahasrabuddhe, Mohammad Imran Siddiqi. Integrated machine learning, molecular docking and 3D-QSAR based approach for identification of potential inhibitors of trypanosomal N-myristoyltransferase. Molecular BioSystems 2016, 12 (12) , 3711-3723. https://doi.org/10.1039/C6MB00574H
  60. Andrew Woodland, Stephen Thompson, Laura A. T. Cleghorn, Neil Norcross, Manu De Rycker, Raffaella Grimaldi, Irene Hallyburton, Bhavya Rao, Suzanne Norval, Laste Stojanovski, Reto Brun, Marcel Kaiser, Julie A. Frearson, David W. Gray, Paul G. Wyatt, Kevin D. Read, Ian H. Gilbert. Discovery of Inhibitors of Trypanosoma brucei by Phenotypic Screening of a Focused Protein Kinase Library. ChemMedChem 2015, 10 (11) , 1809-1820. https://doi.org/10.1002/cmdc.201500300
  61. Daniel Spinks, Victoria Smith, Stephen Thompson, David A. Robinson, Torsten Luksch, Alasdair Smith, Leah S. Torrie, Stuart McElroy, Laste Stojanovski, Suzanne Norval, Iain T. Collie, Irene Hallyburton, Bhavya Rao, Stephen Brand, Ruth Brenk, Julie A. Frearson, Kevin D. Read, Paul G. Wyatt, Ian H. Gilbert. Development of Small‐Molecule Trypanosoma brucei N ‐Myristoyltransferase Inhibitors: Discovery and Optimisation of a Novel Binding Mode. ChemMedChem 2015, 10 (11) , 1821-1836. https://doi.org/10.1002/cmdc.201500301
  62. Takashi Shimada, Makoto Suzuki, Shin-ichi Katakura. Structure of N -myristoyltransferase from Aspergillus fumigatus. Acta Crystallographica Section D Biological Crystallography 2015, 71 (4) , 754-761. https://doi.org/10.1107/S1399004715000401
  63. Megan H. Wright, Daniel Paape, Elisabeth M. Storck, Remigiusz A. Serwa, Deborah F. Smith, Edward W. Tate. Global Analysis of Protein N-Myristoylation and Exploration of N-Myristoyltransferase as a Drug Target in the Neglected Human Pathogen Leishmania donovani. Chemistry & Biology 2015, 22 (3) , 342-354. https://doi.org/10.1016/j.chembiol.2015.01.003
  64. Edward W Tate, Karunakaran A Kalesh, Thomas Lanyon-Hogg, Elisabeth M Storck, Emmanuelle Thinon. Global profiling of protein lipidation using chemical proteomic technologies. Current Opinion in Chemical Biology 2015, 24 , 48-57. https://doi.org/10.1016/j.cbpa.2014.10.016
  65. Martine Keenan, Jason H. Chaplin. A New Era for Chagas Disease Drug Discovery?. 2015, 185-230. https://doi.org/10.1016/bs.pmch.2014.12.001
  66. Wei Huang, Shen Liu, Binhui Chen, Xiao Guo, Yongping Yu. Synthesis of polysubstituted 4-aminopyrazoles and 4-hydroxypyrazoles from vinyl azides and hydrazines. RSC Advances 2015, 5 (41) , 32740-32743. https://doi.org/10.1039/C5RA04371A
  67. Daniel Paape, Andrew S. Bell, William P. Heal, Jennie A. Hutton, Robin J. Leatherbarrow, Edward W. Tate, Deborah F. Smith, . Using a Non-Image-Based Medium-Throughput Assay for Screening Compounds Targeting N-myristoylation in Intracellular Leishmania Amastigotes. PLoS Neglected Tropical Diseases 2014, 8 (12) , e3363. https://doi.org/10.1371/journal.pntd.0003363
  68. Can Zhao, Shutao Ma. Recent Advances in The Discovery of N ‐Myristoyltransferase Inhibitors. ChemMedChem 2014, 9 (11) , 2425-2437. https://doi.org/10.1002/cmdc.201402174
  69. Gilles Eperon, Manica Balasegaram, Julien Potet, Charles Mowbray, Olaf Valverde, François Chappuis. Treatment options for second-stage gambiense human African trypanosomiasis. Expert Review of Anti-infective Therapy 2014, 12 (11) , 1407-1417. https://doi.org/10.1586/14787210.2014.959496
  70. Daniela Begolo, Esteban Erben, Christine Clayton. Drug Target Identification Using a Trypanosome Overexpression Library. Antimicrobial Agents and Chemotherapy 2014, 58 (10) , 6260-6264. https://doi.org/10.1128/AAC.03338-14
  71. Brendan D. Galvin, Zhiru Li, Estelle Villemaine, Catherine B. Poole, Melissa S. Chapman, Michael P. Pollastri, Paul G. Wyatt, Clotilde K. S. Carlow, . A Target Repurposing Approach Identifies N-myristoyltransferase as a New Candidate Drug Target in Filarial Nematodes. PLoS Neglected Tropical Diseases 2014, 8 (9) , e3145. https://doi.org/10.1371/journal.pntd.0003145
  72. Sujeet Kumar, Rajendra K. Sharma. An improved method and cost effective strategy for soluble expression and purification of human N-myristoyltransferase 1 in E. coli. Molecular and Cellular Biochemistry 2014, 392 (1-2) , 175-186. https://doi.org/10.1007/s11010-014-2029-z
  73. Amanda M. Goldston, Aabha I. Sharma, Kimberly S. Paul, David M. Engman. Acylation in trypanosomatids: an essential process and potential drug target. Trends in Parasitology 2014, 30 (7) , 350-360. https://doi.org/10.1016/j.pt.2014.05.003
  74. Ifedayo Victor Ogungbe, William R. Erwin, William N. Setzer. Antileishmanial phytochemical phenolics: Molecular docking to potential protein targets. Journal of Molecular Graphics and Modelling 2014, 48 , 105-117. https://doi.org/10.1016/j.jmgm.2013.12.010
  75. Megan H. Wright, Barbara Clough, Mark D. Rackham, Kaveri Rangachari, James A. Brannigan, Munira Grainger, David K. Moss, Andrew R. Bottrill, William P. Heal, Malgorzata Broncel, Remigiusz A. Serwa, Declan Brady, David J. Mann, Robin J. Leatherbarrow, Rita Tewari, Anthony J. Wilkinson, Anthony A. Holder, Edward W. Tate. Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach. Nature Chemistry 2014, 6 (2) , 112-121. https://doi.org/10.1038/nchem.1830
  76. Jose A. Garcia-Salcedo, Jane C. Munday, Juan D. Unciti-Broceta, Harry P. de Koning. Progress Towards New Treatments for Human African Trypanosomiasis. 2014, 217-238. https://doi.org/10.1007/978-3-7091-1556-5_9
  77. IAN H. GILBERT. Target-based drug discovery for human African trypanosomiasis: selection of molecular target and chemical matter. Parasitology 2014, 141 (1) , 28-36. https://doi.org/10.1017/S0031182013001017
  78. Nick Van Reet, Pati Pyana, Stijn Rogé, Filip Claes, Philippe Büscher. Luminescent multiplex viability assay for Trypanosoma brucei gambiense. Parasites & Vectors 2013, 6 (1) https://doi.org/10.1186/1756-3305-6-207
  79. Juan Carlos Pizarro, Tanya Hills, Guillermo Senisterra, Amy K. Wernimont, Claire Mackenzie, Neil R. Norcross, Michael A. J. Ferguson, Paul G. Wyatt, Ian H. Gilbert, Raymond Hui, . Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design. PLoS Neglected Tropical Diseases 2013, 7 (10) , e2492. https://doi.org/10.1371/journal.pntd.0002492
  80. Ifedayo Victor Ogungbe, Joseph D Ng, William N Setzer. Interactions of antiparasitic alkaloids with Leishmania protein targets: a molecular docking analysis. Future Medicinal Chemistry 2013, 5 (15) , 1777-1799. https://doi.org/10.4155/fmc.13.114
  81. Martine Keenan, Paul W Alexander, Jason H Chaplin, Michael J Abbott, Hugo Diao, Zhisen Wang, Wayne M Best, Catherine J Perez, Scott MJ Cornwall, Sarah K Keatley, RC Andrew Thompson, Susan A Charman, Karen L White, Eileen Ryan, Gong Chen, Jean-Robert Ioset, Thomas W von Geldern, Eric Chatelain. Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi. Future Medicinal Chemistry 2013, 5 (15) , 1733-1752. https://doi.org/10.4155/fmc.13.139
  82. Ifedayo Ogungbe, William Setzer. In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids. Molecules 2013, 18 (7) , 7761-7847. https://doi.org/10.3390/molecules18077761
  83. Samuel A Hasson, James Inglese. Innovation in academic chemical screening: filling the gaps in chemical biology. Current Opinion in Chemical Biology 2013, 17 (3) , 329-338. https://doi.org/10.1016/j.cbpa.2013.04.018
  84. Felix Wilde, Andreas Link. Advances in the design of a multipurpose fragment screening library. Expert Opinion on Drug Discovery 2013, 8 (5) , 597-606. https://doi.org/10.1517/17460441.2013.780022
  85. Boris Rodenko, Harry P. de Koning. Rational Selection of Anti‐Microbial Drug Targets: Unique or Conserved?. 2013, 279-296. https://doi.org/10.1002/9783527670383.ch15
  86. Sebastian S. Gehrke, Erika G. Pinto, Dietmar Steverding, Karin Pleban, Andre G. Tempone, Robert C. Hider, Gerd K. Wagner. Conjugation to 4-aminoquinoline improves the anti-trypanosomal activity of Deferiprone-type iron chelators. Bioorganic & Medicinal Chemistry 2013, 21 (3) , 805-813. https://doi.org/10.1016/j.bmc.2012.11.009
  87. Suman K. Vodnala, Thomas Lundbäck, Birger Sjöberg, Richard Svensson, Martin E. Rottenberg, Lars G. J. Hammarström. In Vitro and In Vivo Activities of 2-Aminopyrazines and 2-Aminopyridines in Experimental Models of Human African Trypanosomiasis. Antimicrobial Agents and Chemotherapy 2013, 57 (2) , 1012-1018. https://doi.org/10.1128/AAC.01870-12
  88. Martín J. Riveira, Babu L. Tekwani, Guillermo R. Labadie, Mirta P. Mischne. Synthesis and biological activity profile of novel 2-cinnamylidene-1,3-diones related to coruscanone A: promising new antileishmanial agents. MedChemComm 2012, 3 (10) , 1294. https://doi.org/10.1039/c2md20143g
  89. Dmitry A. Borkin, Mirela Puscau, Alena Carlson, Agnes Solan, Kraig A. Wheeler, Béla Török, Roman Dembinski. Synthesis of diversely 1,3,5-trisubstituted pyrazoles via 5-exo-dig cyclization. Organic & Biomolecular Chemistry 2012, 10 (23) , 4505. https://doi.org/10.1039/c2ob25580d
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