Optimisation of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity

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

Journal article

Optimisation of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity

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

Bioorganic Chemistry | Published : 2021

DOI: 10.1016/j.bioorg.2021.105244

Abstract

Malaria is a devastating parasitic disease caused by parasites from the genus Plasmodium. Therapeutic resistance has been reported against all clinically available antimalarials, threatening our ability to control the disease and therefore there is an ongoing need for the development of novel antimalarials. Towards this goal, we identified the 2-(N-phenyl carboxamide) triazolopyrimidine class from a high throughput screen of the Janssen Jumpstarter library against the asexual stages of the P. falciparum parasite. Here we describe the structure activity relationship of the identified class and the optimisation of asexual stage activity while maintaining selectivity against the human HepG2 cel..

View full abstract

University of Melbourne Researchers

William Nguyen Author

Christopher Dean Goodman Author

Paola Favuzza Author

Kym Lowes Author

Related Projects (2)

RETARGETING THE ANTIBIOTIC AZITHROMYCIN AS AN ANTIMALARIAL WITH DUAL MODALITY

Malaria parasites resistant to first-line treatments continue to spread in South East Asia. New drugs need to be developed urgently to ensur..

UNDERSTANDING MALARIA IN THE HUMAN HOST

Malaria is one of the worlds most significant health problems and is caused by protozoan parasites of the genus Plasmodium. We aim to unders..

Grants

Awarded by Australian Research Council

Funding Acknowledgements

This work was funded by the National Health and Medical Research Council of Australia (Development Grant 1135421 to B.E.S. and A.F.C.; Project Grant 1143974 to B.E.S., G.I.M, C.D.G. and D.W.W.; Program Grant 1092789 to A.F.C.), the Australian Cancer Research Foundation, the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. We thank and acknowledge the Australian Red Cross Blood Bank for the provision of fresh red blood cells, without which this research could not have been performed. We would like to acknowledge BIO Ventures for Global Health (BVGH) for facilitating a collaboration with Janssen: Pharmaceutical Companies of Johnson & Johnson through WIPO and for sharing the Jumpstarter library for malaria research. A.F.C. is a Howard Hughes International Scholar and an Australia Fellow of the NHMRC. B.E.S. is a Corin Centenary Fellow. D.W.W. is a Hospital Research Foundation Fellow. G.I.M. is an Australian Research Council Laureate Fellow. We thank Dr Andrew Powell for useful discussions.