Lead Optimization of Second-Generation Acridones As Broad-Spectrum Antimalarials
Sponsor
This project was supported by NIH/NIAID (award 1R01AI093784) and DOD/PRMRP (award PR160693/W81XWH-17-2-0041).
Published In
Journal of Medicinal Chemistry
Document Type
Post-Print
Publication Date
6-11-2020
Abstract
The global impact of malaria remains staggering despite extensive efforts to eradicate the disease. With increasing drug resistance and the absence of a clinically available vaccine, there is an urgent need for novel, affordable, and safe drugs for prevention and treatment of malaria. Previously, we described a novel antimalarial acridone chemotype that is potent against both blood-stage and liver-stage malaria parasites. Here, we describe an optimization process that has produced a second-generation acridone series with significant improvements in efficacy, metabolic stability, pharmacokinetics, and safety profiles. These findings highlight the therapeutic potential of dual-stage targeting acridones as novel drug candidates for further preclinical development.
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DOI
10.1021/acs.jmedchem.0c00539
Persistent Identifier
https://archives.pdx.edu/ds/psu/34035
Citation Details
Kancharla, P., Dodean, R. A., Li, Y., Pou, S., Pybus, B., Melendez, V., Read, L., Bane, C. E., Vesely, B., Kreishman-Deitrick, M., Black, C., Li, Q., Sciotti, R. J., Olmeda, R., Luong, T.-L., Gaona, H., Potter, B., Sousa, J., Marcsisin, S., … Kelly, J. X. (2020). Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials. Journal of Medicinal Chemistry, 63(11), 6179–6202. https://doi.org/10.1021/ACS.JMEDCHEM.0C00539
Description
This is the Author's Accepted Manuscript of an article that was subsequently published in Journal of Medicinal Chemistry, Volume 63, June 2020, published by American Chemical Society. The version of record may be found at https://doi.org/10.1021/acs.jmedchem.0c00539