Details

Autor(en) / Beteiligte

• 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

Titel

Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials

Ist Teil von

• Journal of medicinal chemistry, 2020-06, Vol.63 (11), p.6179-6202

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.