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
- 12 February 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 64 (4), 2291-2309
- https://doi.org/10.1021/acs.jmedchem.1c00034
Abstract
A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure–activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (P. falciparum cyclic amine resistance locus in the mode of resistance.Keywords
Funding Information
- Medicines for Malaria Venture
- South African Technology Innovation Agency
- National Institute of Health
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