Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials
In: Journal of Medicinal Chemistry, Jg. 63 (2020-06-11), Heft 11, S. 6179-6202
Online
serialPeriodical
Zugriff:
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.
Titel: |
Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials
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Autor/in / Beteiligte Person: | Kancharla, Papireddy ; Dodean, Rozalia A. ; Li, Yuexin ; Pou, Sovitj ; Pybus, Brandon ; Melendez, Victor ; Read, Lisa ; Bane, Charles E. ; Vesely, Brian ; Kreishman-Deitrick, Mara ; Black, Chad ; Li, Qigui ; Sciotti, Richard J. ; Olmeda, Raul ; Luong, Thu-Lan ; Gaona, Heather ; Potter, Brittney ; Sousa, Jason ; Marcsisin, Sean ; Caridha, Diana ; Xie, Lisa ; Vuong, Chau ; Zeng, Qiang ; Zhang, Jing ; Zhang, Ping ; Lin, Hsiuling ; Butler, Kirk ; Roncal, Norma ; Gaynor-Ohnstad, Lacy ; Leed, Susan E. ; Nolan, Christina ; Ceja, Frida G. ; Rasmussen, Stephanie A. ; Tumwebaze, Patrick K. ; Rosenthal, Philip J. ; Mu, Jianbing ; Bayles, Brett R. ; Cooper, Roland A. ; Reynolds, Kevin A. ; Smilkstein, Martin J. ; Riscoe, Michael K. ; Kelly, Jane X. |
Link: | |
Zeitschrift: | Journal of Medicinal Chemistry, Jg. 63 (2020-06-11), Heft 11, S. 6179-6202 |
Veröffentlichung: | 2020 |
Medientyp: | serialPeriodical |
ISSN: | 0022-2623 (print) ; 1520-4804 (print) |
DOI: | 10.1021/acs.jmedchem.0c00539 |
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