Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts

Author:

Le Manach Claire1,Dam Jean1,Woodland John G.1,Kaur Gurminder1,Khonde Lutete P.1,Brunschwig Christel2,Njoroge Mathew2ORCID,Wicht Kathryn J.3,Horatscheck André1,Paquet Tanya1,Boyle Grant A.1,Gibhard Liezl2,Taylor Dale2,Lawrence Nina2,Yeo Tomas3,Mok Sachel3ORCID,Eastman Richard T.4ORCID,Dorjsuren Dorjbal4,Talley Daniel C.4,Guo Hui4,Simeonov Anton4,Reader Janette5,van der Watt Mariëtte5,Erlank Erica67,Venter Nelius67,Zawada Jacek W.67,Aswat Ayesha67,Nardini Luisa67,Coetzer Theresa L.8,Lauterbach Sonja B.8,Bezuidenhout Belinda C.8,Theron Anjo9,Mancama Dalu9,Koekemoer Lizette L.67,Birkholtz Lyn-Marie5,Wittlin Sergio1011,Delves Michael1213,Ottilie Sabine14ORCID,Winzeler Elizabeth A.14,von Geldern Thomas W.15,Smith Dennis16,Fidock David A.317,Street Leslie J.1,Basarab Gregory S.1ORCID,Duffy James18,Chibale Kelly119ORCID

Affiliation:

1. Drug Discovery and Development Center (H3D), University of Cape Town, Rondebosch 7701, South Africa

2. Drug Discovery and Development Center (H3D), Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory 7925, South Africa

3. Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States

4. Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland 20892, United States

5. Department of Biochemistry, Genetics and Microbiology, Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, Pretoria 0028, South Africa

6. Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa

7. Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2192, South Africa

8. Wits Research Institute for Malaria, School of Pathology, Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa

9. Biosciences, Council for Scientific and Industrial Research, P.O. Box 395, Pretoria 0001, South Africa

10. Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland

11. University of Basel, 4003 Basel, Switzerland

12. Imperial College London, South Kensington, London SW7 2AZ, U.K.

13. London School of Hygiene and Tropical Medicine, London WC1E 7HT, U.K.

14. Division of Host−Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-076, United States

15. Embedded Consulting, P.O. Box 726, Richmond, Illinois 60071, United States

16. 4 The Maltings, Walmer CT14 7AR, U.K.

17. Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York 10032, United States

18. Medicines for Malaria Venture, ICC, Route de Pré-Bois 20, P.O. Box 1826, 1215 Geneva, Switzerland

19. South African Medical Research Council, Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa

Funder

Medicines for Malaria Venture

South African Technology Innovation Agency

National Institute of Health

Publisher

American Chemical Society (ACS)

Subject

Drug Discovery,Molecular Medicine

Reference37 articles.

1. WHO. Global Technical Strategy for Malaria 2016–2030; World Health Organization: Geneva, 2015.

2. WHO. World Malaria Report 2019; World Health Organization: Geneva, 2019.

3. Researchers and WHO clash over global threat of drug resistant malaria

4. WHO. World Malaria Report 2020; World Health Organization: Geneva, 2020.

5. New developments in anti-malarial target candidate and product profiles

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