Structure-Guided Optimization of Novel Inhibitors of Plasmodium Lysyl-tRNA Synthetase with Multistage Activity against Malaria Parasites.

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Title: Structure-Guided Optimization of Novel Inhibitors of Plasmodium Lysyl-tRNA Synthetase with Multistage Activity against Malaria Parasites.
Authors: Forte B; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Bellany F; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Campbell PS; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Chemi G; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Dawson A; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Anderson M; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Aniweh Y; West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), College of Basic and Applied Sciences, University of Ghana, Accra LG54, Ghana., Burkhard AY; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Aguiar ACC; Department of Microbiology, Immunology, and Parasitology, Federal University of São Paulo, São Paulo, São Paulo CEP 04023-062, Brazil., Churchyard A; Department of Life Sciences, Imperial College, London SW7 2AZ, U.K., Cooper CA; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30602-0002, United States., Dos Santos Ferreira A; Oswaldo Cruz Foundation, Leishmaniasis and Malaria Bioassay Platform, Porto Velho, Rondônia CEP 76812-245, Brazil., Famodimu MT; Department of Life Sciences, Imperial College, London SW7 2AZ, U.K.; Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, U.K., Fang FG; Eisai, Inc., 35 Cambridge Park Drive Suite 200, Cambridge, Massachusetts 02140, United States., Hu X; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Huijs T; TropIQ Health Sciences, Nijmegen 6534 AT, The Netherlands., Baud D; MMV Medicines for Malaria Venture, ICC, Geneva 1215, Switzerland., Jansen C; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Jiménez Díaz MB; The Art of Discovery, Derio 48160, Spain., Bonnert R; MMV Medicines for Malaria Venture, ICC, Geneva 1215, Switzerland., Boyd S; MMV Medicines for Malaria Venture, ICC, Geneva 1215, Switzerland., Crespo-Fernández B; Global Health Medicines R&D, GSK, Tres Cantos, Madrid 28760, Spain., Mitasev B; Eisai, Inc., 35 Cambridge Park Drive Suite 200, Cambridge, Massachusetts 02140, United States., Montagna S; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Mok S; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States.; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Murugesan D; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Narwal SK; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Norcross NR; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Okombo J; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Park H; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States.; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Peet C; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Pereira DB; Research Center in Tropical Medicine of Rondônia, Porto Velho, Rondônia CEP 76812-329, Brazil., Post JM; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Reader J; Department of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control University of Pretoria, Hatfield, Pretoria 0028, South Africa., Riley J; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Robinson DA; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Shinkyo R; Eisai, Inc., 35 Cambridge Park Drive Suite 200, Cambridge, Massachusetts 02140, United States., Simeons FRC; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Simpson L; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Smith A; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Smith D; MMV Medicines for Malaria Venture, ICC, Geneva 1215, Switzerland., Striepen J; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Teles CBG; Oswaldo Cruz Foundation, Leishmaniasis and Malaria Bioassay Platform, Porto Velho, Rondônia CEP 76812-245, Brazil., van der Laak R; TropIQ Health Sciences, Nijmegen 6534 AT, The Netherlands., Uhlemann AC; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States.; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Vantaux A; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh 120210, Cambodia., Wilson C; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Witkowski B; São Carlos Institute of Physics, University of São Paulo, São Carlos, São Paulo CEP 13563-120, Brazil., Wood G; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Yeo T; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Zuccotto F; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Angulo-Barturen I; The Art of Discovery, Derio 48160, Spain., Baum J; Department of Life Sciences, Imperial College, London SW7 2AZ, U.K., Bolscher JM; TropIQ Health Sciences, Nijmegen 6534 AT, The Netherlands., Guido RVC; São Carlos Institute of Physics, University of São Paulo, São Carlos, São Paulo CEP 13563-120, Brazil., Birkholtz LM; Department of Biochemistry, Stellenbosch University, Stellenbosch, Matieland 7602, South Africa., Delves MJ; Department of Life Sciences, Imperial College, London SW7 2AZ, U.K.; Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, U.K., Dembele L; Univerité Des Sciences, Des Techniques Et Des Technologies de Bamako (USTTB), Parasite and Microbe Research and Training Centre (P-MRTC), Faculty of Pharmacy, Point G, Bamako BP 1805, Mali., Fidock DA; Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States.; Center for Malaria Therapeutics and Antimicrobial Resistance, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States.; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States., Gamo FJ; Global Health Medicines R&D, GSK, Tres Cantos, Madrid 28760, Spain., Kyle DE; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30602-0002, United States., Maher SP; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30602-0002, United States., Popovici J; Malaria Research Unit, Institut Pasteur du Cambodge, Phnom Penh 120210, Cambodia.; Infectious Disease Epidemiology and Analytics G5 Unit, Institut Pasteur, Université Paris Cité, Paris 75015, France., Walpole C; Structural Genomics Consortium, Research Institute of the McGill University Health Centre, Montreal, Québec H4A 3J1, Canada., Gusovsky F; Eisai, Inc., 35 Cambridge Park Drive Suite 200, Cambridge, Massachusetts 02140, United States., Willis PA; MMV Medicines for Malaria Venture, ICC, Geneva 1215, Switzerland., Read KD; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Gilbert IH; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K., Baragaña B; Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Source: Journal of medicinal chemistry [J Med Chem] 2026 Jun 11; Vol. 69 (11), pp. 13820-13855. Date of Electronic Publication: 2026 Jun 02.
Publication Type: Journal Article
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.6c00823